Pulmonary Atresia With Intact Ventricular Septum 

Updated: Dec 27, 2020
Author: John R Charpie, MD, PhD; Chief Editor: Howard S Weber, MD, FSCAI 

Overview

Background

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

Pathophysiology

The pulmonary atresia with intact ventricular septum (PAIVS) spectrum ranges from a normal-sized or slightly hypoplastic tripartite right ventricle with a well-formed infundibulum and imperforate pulmonary valve with commissural fusion to a diminutive unipartite right ventricle, narrowed or atretic infundibulum, primitive pulmonary valve, and ventriculocoronary artery connections (with or without stenoses). In PAIVS, the tricuspid valve is rarely 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 that originate from the descending thoracic aorta are rare.

Etiology

As with many forms of congestive heart disease (CHD), the genetic cause of pulmonary atresia with intact ventricular septum (PAIVS) is unknown. Kutsche and Van Mierop suggest that PAIVS probably occurs relatively late in cardiac morphogenesis after cardiac septation compared with pulmonary atresia with ventricular septal defect.[1]  This may reflect a prenatal inflammatory or infectious condition; however, no histopathological evidence currently supports this view.

In rare familial cases, some researchers advocate a single gene theory.

Epidemiology

United States statistics

Despite overall low prevalence, pulmonary atresia with intact ventricular septum (PAIVS) is one form of cyanotic congenital heart disease (CCHD) that usually presents during the immediate neonatal period as the ductus arteriosus closes (along with transposition of the great arteries, tricuspid atresia, 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).

International statistics

PAIVS occurs in 4.5 per 100,000 live births in the United Kingdom and Ireland.

Age-related demographics

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

Prognosis

Although outcomes have improved, surgical procedures (biventricular or univentricular strategies) are still associated with high mortality and morbidity.[2]  Prognosis depends on the specific anatomy and type of intervention (univentricular, 1.5-ventricle, or biventricular correction). Overall survival is approximately 64-76% at age 5 years; however, single institutions report improved intermediate-term outcomes in relatively small series.

Karamlou et al[3]  reported long-term functional health status and exercise capacity in 122 patients with pulmonary atresia with intact ventricular septum (PAIVS) following univentricular, 1.5-ventricle, or biventricular repair (mean 14 y). Participants had lower functional health status scores in domains of physical functioning compared with age- and sex-matched normal controls. Exercise capacity was higher in 1.5-ventricle repair patients, whereas functional health status measures were higher in biventricular repair patients. Peak oxygen consumption was low across all groups and correlated with larger initial tricuspid valve z-score.

Morbidity/mortality

Early survival depends on maintaining ductal patency until a palliative procedure can be performed to establish a reliable source of pulmonary blood flow. In those cases with an adequate-size right ventricle, transcatheter perforation of the pulmonary valve and maintaining patency of the ductus arteriosus can result in a biventricular circulation without the need for surgical intervention. In those cases requiring an additional source of pulmonary blood flow for an extended time period, placement of a systemic-to-pulmonary artery shunt or arterial ductal stenting may be appropriate in selected cases.[4, 5]

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 64-76% at age 5 years, which is directly dependent on the degree of right heart hypoplasia. Note the following:

  • Sudden death, angina, and arrhythmias: PAIVS is associated with ventriculocoronary connections in approximately 45% of patients and correlates directly with the severity of right heart hypoplasia. Because coronary artery stenoses are present 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 compared with patients who have other forms of congenital heart disease (CHD).

  • CHF: Depending on the particular anatomic substrate, these patients may have an early predilection for heart failure due to both tricuspid regurgitation and increased pulmonary blood flow via a large systemic-to-pulmonary artery shunt. Postoperatively, the risk of heart failure may continue, depending on 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). Most late reoperations following biventricular repair are pulmonary valve replacements.

  • 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.

Complications

As noted above, complications of PAIVS include the following:

  • CHF

  • Sudden death

  • Arrhythmia

  • Cyanosis

Patient Education

Provide cardiopulmonary resuscitation (CPR) instruction to family members.

Educate family members about congenital heart disease (CHD).

Consider fetal echocardiography and genetics counseling for future pregnancies.[6]

 

Presentation

History and Physical Examination

History

Infants with pulmonary atresia with intact ventricular septum (PAIVS) are usually born at term, and cyanosis is apparent within hours. The diagnosis can be made prenatally using fetal echocardiography. These babies develop early progressive cyanosis and tachypnea associated with closure of the patent ductus arteriosus.

Physical examination

The most common finding upon physical examination is central (perioral and periorbital) cyanosis. Following ductal closure, profound generalized cyanosis is present. Also note the following:

  • Apical left ventricular impulse may be pronounced.

  • The first and second heart sounds are single.

  • A pansystolic murmur is often 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 are usually present but can be bounding in the setting of a large patent ductus arteriosus and increased pulmonary blood flow.

  • Hepatomegaly is uncommon unless the atrial septal defect is restrictive (rare).

 

DDx

 

Workup

Laboratory Studies

No laboratory blood tests help to confirm a specific diagnosis of pulmonary atresia with intact ventricular septum (PAIVS).

Pulse oximetry will demonstrate similar hypoxemia in both the upper and lower extremities.

An arterial blood gas (ABG) study is likely to show hypoxemia and hypocarbia refractory to inspired oxygen concentration, consistent with cyanotic congenital heart disease (CCHD) and a fixed right-to-left shunt.

Imaging Studies

Electrocardiography

Electrocardiography (ECG) often reveals 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.

Echocardiography and Doppler

Echocardiography and angiography are the two most important studies in diagnosis of pulmonary atresia. Two-dimensional echocardiography is diagnostic for pulmonary atresia with intact ventricular septum (PAIVS).[7] A combination of subcostal and precordial views reveals anatomic pulmonary atresia in addition to tricuspid valve and right ventricular morphology and size.

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) was highly correlated with size of the right ventricular cavity. In addition, retrospective data suggest that the degree of right ventricular hypoplasia was the most important determinant in a single-ventricle versus two-ventricle repair.

In addition, color-flow and continuous-wave Doppler ultrasonographic studies reveal the degree of tricuspid regurgitation, allow the estimation of right ventricular pressure which is typically suprasystemic, and reveal restriction of the interatrial communication (uncommon).

A combination of imaging and Doppler echocardiography reveals branch pulmonary artery size and configuration (usually within reference ranges), as well as ductal patency. Echocardiographic imaging may reveal ventriculocoronary connections (coronary sinusoids) but has limited use for identifying coronary artery stenoses and right ventricular–dependent coronary circulation.

Angiocardiography

The prognosis of a neonate 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 additional information about the size and morphology of the right ventricle.

Balloon occlusion aortography reveals the proximal coronary arteries and coronary arterial stenosis or interruption.

Radiography

Chest radiography usually reveals mild cardiomegaly and decreased or normal pulmonary vascular markings.

With severe tricuspid regurgitation (and a dysplastic tricuspid valve), profound cardiomegaly due to right atrial enlargement may be present.

Procedures

Cardiac catheterization

Cardiac catheterization confirms the right ventricular pressure measurement and anatomic pulmonary valve atresia.

Ventriculocoronary connections are best delineated with cardiac catheterization.

In the rare instance of a restrictive atrial communication, a transcatheter balloon or blade atrial septostomy will maintain adequate cardiac output. Transcatheter wire puncture, laser perforation,[8] and radiofrequency-assisted balloon pulmonary valvotomy have been used as alternatives to surgical valvotomy in patients with pulmonary atresia with intact ventricular septum (PAIVS) and acceptable tricuspid valve and right ventricular size. However, despite the fact that a technically adequate valvotomy can be achieved in a high percentage of patients, catheter-related complications are not rare and maintaining patency of the ductus arteriosus is necessary for a time period as an additional source of pulmonary blood flow until right ventricular hypertrophy regresses and compliance improves.

In a retrospective study of 129 infants born with critical pulmonary stenosis or membranous PAIVS, Ronai et al found that left ventricular dysfunction following pulmonary valve balloon dilation occurred in 35% of the infants and could be severe but resolved.[9] In multivariable analysis, lower pulmonary valve z-score, preexisting moderate or severe tricuspid regurgitation, and larger right ventricular apical area were predictive of postprocedure left ventricular dysfunction, with those who had larger right ventricles at the greatest risk.[9]

See the image below.

The heart catheterization. The heart catheterization.

Histologic Findings

Patients with pulmonary atresia with intact ventricular septum (PAIVS) can demonstrate a wide range of right ventricular 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

Approach Considerations

Early decision making on the management goal is crucial, as determined by individual morphologic characteristics at presentation, and outcomes may be improved by right ventricular development at a later time point is taken into consideration.[10] Note the following:

  • Consult with a pediatric cardiologist and pediatric cardiothoracic surgeon for the management of patients with pulmonary atresia with intact ventricular septum (PAIVS).

  • Admit patients with PAIVS for future preoperative testing and surgical interventions. Note that pulmonary valve replacement constitutes most late reoperations. Transfer is required for specialized diagnostic evaluation and surgical intervention.

  • Possible discharge medications include digoxin, furosemide, and aspirin. Outpatient management requires carefully monitoring of medication doses and adverse effects. In addition, monitor the adequacy of repair/palliation with pulse oximetry and periodic echocardiography.

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

  • No specific activity restrictions are necessary.[11]

Medical Care

Initial treatment of pulmonary atresia with intact ventricular septum (PAIVS) consists of maintaining ductal patency with a continuous intravenous prostaglandin E1 infusion.

To correct metabolic acidosis in a neonate, replace fluids and administer sodium bicarbonate. Mechanical ventilation may be necessary if acidosis persists and apnea occurs secondary to prostaglandin E1.

Patients ultimately require surgical palliation or therapeutic catheterization prior to hospital discharge.

Surgical Care

An optimal strategy for definitive repair has yet to be defined.[2] Surgical or catheter-based interventional algorithms for pulmonary atresia with intact ventricular septum (PAIVS) depend on the size and morphology of both the tricuspid valve and the right ventricle, as well as the presence of abnormal coronary artery anatomy.

In a retrospective study, Rathgeber et al reviewed all cases of PAIVS treated with radiofrequency perforation (RFP) at a single center from 1999 through 2012 (n = 18) to determine the safety and efficacy of RFP and to assess the pre-intervention anatomical parameters associated with a biventricular outcome. Seventeen procedures were successful; all patients were alive at the most recent follow-up (median: 4.9 years), 12 (71%) had a biventricular circulation, 2 (12%) had a 1½ ventricle repair, 2 (12%) had a univentricular repair, and 1 was lost to follow-up. In the investigators’ cohort of patients, the pre-intervention tricuspid valve/mitral valve (TV/MV) ratio and tricuspid valve (TV) z-score were found to be predictors of a biventricular outcome.[12]

In a retrospective study, Zheng et al reviewed their 15-year experience in the management of PAIVS. The patients (n = 170) were divided into two groups: the one-stage surgery group (n = 33) and the staged surgery group (n = 137), in which patients received definitive repair, including biventricular repair, 1.5 ventricular repair and univentricular palliation without or with initial intervention. In the one-stage surgery group, 3 patients died postoperation; the estimated 1-, 5- and 15-year survival rates were 97.0%, 93.7%, and 88.5%, respectively. In the staged surgery group, 23 patients died; the estimated 1-, 5- and 15-year survival rates were 89.8%, 88.2%, and 69.1%, showing no significant difference from the one-stage surgery group.[13]

Invasive fetal cardiac intervention is a novel approach to the management of PAIVS. Fetal pulmonary valvuloplasty has been performed at several institutions with varying degrees of success.[14, 15] Hogan et al reviewed International Fetal Cardiac Intervention Registry data to evaluate the fetal and maternal characteristics, the technical aspects of the procedure, as well as pregnancy and neonatal outcome data.[14] The procedure was considered successful in 41 of 58 (71%) cases. Nine fetuses died (7 periprocedure and two >48 hrs postprocedure). The authors noted extreme variation among center criteria for the procedure and recommend prospective case-controlled studies using uniform criteria to increase the likelihood of successful outcomes.[14]

Mild tricuspid valve and right ventricular hypoplasia without ventriculocoronary connections

Perform transcatheter valvotomy, with or without stenting of the patent ductus arteriosus or surgical systemic-to-pulmonary artery shunt placement.

In 10 neonates with PAIVS, Li and colleagues showed that pulmonary valve perforation and balloon valvuloplasty through the right ventricle was a safe and feasible alternative to surgical valvotomy.[16] If the right ventricle and tricuspid valve grow, a two-ventricle correction is probable in the future.

One-stage definitive repair has been described in two infants.[17] The repair comprised resection of hypertrophied muscles in the outflow and trabecular portions of the right ventricle (right ventricular overhaul technique), surgical valvotomy or transannular patch, and adjustable snare-closure of the foramen ovale.

A study by Chubb et al summarized long-term followup of 39 patients with PA/IVS who underwent valve perforations with or without stenting of the arterial duct. There were 8 deaths (21%), and 25 patients (83% of survivors) had a biventricular circulation despite small median tricuspid valve Z-scores.[18]

Hasan and colleagues[19] reviewed the short- and medium-term outcome of transcatheter pulmonary valve perforation in 50 patients with PAIVS and non–right ventricular–dependent coronary circulation. Pulmonary valve perforation was attempted in 30 patients, and 26 had a successful procedure. Twenty-four patients had surgery without pulmonary valve perforation. Complications of pulmonary valve perforation included myocardial perforation in 17% of patients. There were no deaths in the entire cohort. Tricuspid valve z-scores were larger in the nonsurgical patients, and all patients in the nonsurgical group achieved a biventricular circulation at a median follow-up of 4.3 years.

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 1.5-ventricle or 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 1.5-ventricle or 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.

 

Medication

Medication Summary

No specific drug therapies address pulmonary atresia with intact ventricular septum (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 and surgical systemic-to-pulmonary artery shunts should receive low-dose aspirin therapy.

Inotropic agents

Class Summary

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

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.

Loop diuretics

Class Summary

These agents inhibit electrolyte reabsorption in the thick ascending limb of the Henle loop in the kidney, thus promoting diuresis.

Furosemide (Lasix)

Commonly used loop diuretic; has moderate diuretic potency.

Prostaglandins

Class Summary

PGE1 is used for treatment of ductal dependent cyanotic congenital heart disease, which is due to decreased pulmonary blood flow.

Alprostadil IV (Prostin VR)

Relaxes smooth muscle of the ductus arteriosus. Beneficial in infants with congenital defects that restrict pulmonary or systemic blood flow and who depend on a patent ductus arteriosus to achieve adequate oxygenation and lower body perfusion.