Infundibular Pulmonary Stenosis

Updated: Nov 23, 2022
Author: Poothirikovil Venugopalan, MBBS, MD, FRCPCH; Chief Editor: Stuart Berger, MD 

Overview

Background

First described by Elliotson, infundibular pulmonary stenosis (IPS) refers to obstruction of outflow from the right ventricle (RV) within the body of the RV, as opposed to obstruction at the pulmonary valve, pulmonary artery (PA), or its branches. IPS often occurs in association with other intracardiac anomalies; isolated IPS is rare. In this article, IPS refers to isolated infundibular pulmonary stenosis with an intact ventricular septum.

Pathophysiology

Infundibular pulmonary stenosis (IPS) has two forms. In the more common type, stenosis of the proximal portion of the infundibulum is due to a fibrous or muscle band at the junction of the main cavity of the right ventricle (RV) and the infundibulum. The band divides the cavity into two chambers. The second type is associated with a thickened muscular infundibulum that forms a narrow outlet to the RV. The infundibulum appears shrunken. In this second type, the narrowed area may be short or long and may be located immediately below the pulmonary valve or lower into the outflow tract.

IPS is often associated with a ventricular septal defect (VSD). Common opinion holds that the VSD closes, leaving behind an isolated IPS. Whether some children have excessive muscle without ever having had a VSD is not known.

The hemodynamic consequence of the obstruction is elevated pressure within the RV cavity. The degree of elevation depends on the severity of obstruction. When severe, the resulting RV systolic pressure may exceed that of the left ventricle (LV). This high pressure is limited to the portion proximal to the infundibulum. Lower or even normal pressures are present beyond the obstruction site. Reactive RV hypertrophy follows.

Subsequent elevation of end-diastolic pressure and decreased compliance of the RV, consequent to the hypertrophy, lead to elevated right atrial (RA) pressure and dilatation of that chamber. Greater RA pressures are required to fill the ventricle, and relative right and left atrial pressures may be reversed, favoring persistent patency of the foramen ovale and right-to-left shunting. This gives rise to central cyanosis. Such reversal and cyanosis can occur when the RV is hypoplastic, even with less severe pulmonary stenosis.

In neonates with severe pulmonary stenosis, the pulmonary blood flow depends on the patency of the ductus arteriosus. The RV becomes hypertrophic and maintains cardiac output to a very advanced stage. With exercise, the requirement for cardiac output increases, and RV pressure proportionately rises until it exceeds the capacity of the RV muscle.

Deformity and malfunctioning of the LV occur in proportion to RV hypertension and can be demonstrated using sophisticated techniques. These LV problems have little practical consequence because they improve with relief of the RV hypertension.

Reduced LV end-diastolic compliance has been chiefly ascribed to displacement of the interventricular septum into the LV cavity. The mechanisms responsible for systolic dysfunction are less clear.

Patients with isolated valvular pulmonary stenosis may have a reactive infundibular hypertrophy that could elicit a reactive infundibular obstruction. This obstruction might persist for a variable period following relief of the valvar obstruction.

IPS can cause anatomic and, possibly, functional changes in the developing pulmonary vascular bed. Experimental construction of the pulmonary trunk in fetal lambs is accompanied by relatively thin-walled PA resistance vessels. Some researchers postulate this decreased medial muscular layer is caused by a higher oxygen tension of the blood perfusing the fetal pulmonary circulation.

IPS has been noted to develop in a fetus following twin-to-twin transfusion, and authors have, in that case, postulated that the elevated blood volume/pressure may be a factor in the pathogenesis.[1] Inversin, the product of the inv locus, may have a specific role in cardiac morphogenesis (especially in the development of IPS) in addition to its contribution to situs determination.

Epidemiology

Incidence

In the United States, the relative frequency of infundibular pulmonary stenosis (IPS) among all obstructive lesions of the right ventricle outflow tract is 2-10%.

Internationally, no reliable figures have been reported.

Sex- and age-related demographics

IPS has no sex predilection.

IPS is present from birth, although most patients are asymptomatic. The severity of stenosis can progress with age.[2]

Prognosis

Morbidity/mortality

The prognosis of infundibular pulmonary stenosis (IPS) mainly depends on the severity of stenosis in the absence of any additional lesions.

Patients with mild-to-moderate stenosis live normal lives with no symptoms, apart from the risk of IE.

Severely affected patients are at risk of death at any time throughout their lives. Patients at highest risk are those with symptoms in the first year of life, as well as those with congestive cardiac failure or paroxysmal dyspneic episodes.

Severe IPS that leads to atresia can result in neonatal death when the ductus arteriosus constricts. Heart failure secondary to IPS is rare in childhood beyond early infancy. Exercise may provoke syncope and even sudden death in severe stenosis. The stenosis may remain asymptomatic but may progress to require intervention in adulthood.

Complications

Complications of pulmonary stenosis include the following:

  • Increasing severity of stenosis

  • Endocarditis

  • Significant residual pulmonary regurgitation and right heart failure (rare)

  • RV infarction

  • RV endocardial fibroelastosis

  • Cardiac arrhythmias

  • Syncope

  • Sudden death

  • Pulmonary artery aneurysm formation[3]

Patient Education

Educate patients about the disease and its natural history, as well as the importance of good oral hygiene.

Make patients aware of the need for regular follow-up.

Patients should also be aware of the need for endocarditis prophylaxis during dental and other surgical procedures.

 

Presentation

History

Infundibular pulmonary stenosis (IPS) manifestations depend on the severity of obstruction and presence or absence of associated cardiac anomalies. They may include the following:

  • Most children grow well and are asymptomatic, even when stenosis is moderate or severe.

  • The murmur is discovered on routine auscultation, usually at birth, although cyanosis may lead to discovery of maximum obstruction.

  • Symptoms are rare in infants, with the notable exception of patients with critical stenosis.

  • Subjective complaints tend to increase with age.

  • Dyspnea and fatigue are the most common symptoms.

  • Exertion may provoke syncope or even death.

  • Precordial pain is common, and epigastric pain is often present.

  • Frank right-sided heart failure occasionally occurs in infancy or early childhood.

  • Squatting is extremely rare in children with isolated PS (compared with tetralogy of Fallot)

Physical Examination

Physical examination findings may include the following:

  • Growth and development are usually normal. Frank heart failure is rarely evident.

  • Chest asymmetry occasionally accompanies severe stenosis, but precordial bulge is uncommon.

  • Jugular venous pulse shows larger a waves as the degree of obstruction increases. These presystolic pulsations may be felt during palpation of the liver, even without evidence of cardiac failure.

  • Prominent left parasternal heave occurs if pulmonary stenosis is significant.[4]

  • A systolic thrill is present at the second and third left intercostal space near the sternum. Occasionally, the thrill may disappear with onset of failure.

Auscultation

The first heart sound is normal.

The pulmonic valve component (P-2) of the second heart sound is soft and delayed in moderate-to-severe stenosis. Note the following features:

  • The degree of split is proportionate to the severity of the obstruction; the greater the obstruction, the longer the right ventricle takes to empty and the wider the split.

  • P-2 decreases in intensity in proportion to the pressure in the pulmonary artery. The lower the pressure, the softer the P-2. P-2 may be inaudible with maximal obstruction.

  • In severe stenosis with unchanging cardiac output, the split may be fixed. A loud pansystolic crescendo-decrescendo murmur (ejection type), with its maximal intensity at mid systole or later (indistinguishable from that of isolated pulmonary valve stenosis [PVS]), is heard at the left sternal border and is well-conducted to the precordium, neck, and back.

A third heart sound is audible in the presence of an associated atrial septal defect (ASD) or anomalous pulmonary vein.

A fourth heart sound is heard at the lower left sternal border in severe cases. This fourth heart sound is associated with a large a wave in the right atrium and usually indicates a severe lesion.

Note the absence of the ejection click that characterizes valvar pulmonary stenosis.

A loud, long, systolic crescendo-decrescendo murmur (ejection type), with its maximal intensity at mid systole or later (indistinguishable from that of isolated PVS), is heard at the left sternal border and is well-conducted to the precordium, neck, and back. Note the following features:

  • The murmur, although louder at the second and third left intercostal space, may be heard well at the low left sternal border.

  • The later the peak intensity of the murmur occurs, the greater the obstruction.

  • Although murmur loudness does not necessarily increase with severity, murmurs of less than grade 3/6 usually occur with mild stenosis. With moderate-to-severe stenosis, murmurs are usually systolic and grade 4/6 or louder.

  • The length of the murmur depends on duration of RV systole that, in turn, depends on severity of the stenosis. Thus, mild stenosis is associated with a short murmur, with its peak earlier than mid systole. In moderate stenosis, the murmur ends at or slightly after the aortic component of the second heart sound, which remains audible. With marked-to-severe obstruction, the murmur extends beyond the aortic component, which may be obscured.

Critical stenosis

Infants with critical stenosis present with variable findings, including the following:

  • Heart failure is prominent.

  • A small infant with maximal obstruction may have minimal murmur (sometimes overlooked) and cyanosis.

  • An additional systolic murmur is heard in the lower left parasternal region from the tricuspid regurgitation.

  • Absence of P-2 along with the presence of cardiomegaly and the holosystolic murmur of tricuspid regurgitation highly suggests a critical pulmonary stenosis diagnosis.

 

DDx

Diagnostic Considerations

Important considerations

Do not presume asymptomatic patients to have mild stenosis without detailed evaluation.

Avoid diagnosing mild stenosis because of the absence of pulmonary oligemia on chest radiography.

Avoid missing associated lesions, such as coexisting valve or supravalvar stenosis, ventricular septal defect, atrial septal defect, and hypoplasia of the right ventricle.

Avoid confusing pulmonary stenosis with double-outlet right ventricle.

Other problems to be considered

Consider the following conditions in the differential diagnosis in patients with suspected infundibular pulmonary stenosis:

  • Tumors of right ventricular outflow tract

  • Aneurysm of right coronary sinus

  • Right ventricular myxomas

  • Pulmonary artery stenosis (unilateral, bilateral, single or multiple, localized or diffuse)

  • Pulmonary artery branch stenosis

  • Left ventricular noncompaction[5]

  • Glycogen-Storage Disease Type I (Von Gierke disease)

Differential Diagnoses

 

Workup

Laboratory Studies

Blood work investigations are helpful in acute-stage management when an infant presents with cyanosis or heart failure.

Imaging Studies

Chest radiography

Findings on chest radiography may include the following:

  • Heart size is usually within reference ranges but, at times, may be slightly enlarged. Pulmonary vasculature is reduced in patients with cyanosis or in those with cardiac failure (see image below).

    Infundibular Pulmonary Stenosis. Chest radiograph Infundibular Pulmonary Stenosis. Chest radiograph of a 2-year-old boy with severe pulmonary stenosis (infundibular). Note the mild cardiomegaly, reduced pulmonary vascularity, and absence of poststenotic dilatation of pulmonary artery.
  • Cardiomegaly or dilatation of the right ventricle may be evident in severe cases and becomes more marked with tricuspid regurgitation or cardiac failure.

  • Pulmonary vascularity is usually normal, except in severe cases with right-to-left shunt across the atrial or ventricular septa.

  • In infants with severe or critical pulmonary stenosis, cardiomegaly with a huge cardiac silhouette is the rule. Pulmonary vascular markings are also reduced.

  • Poststenotic dilation of the main pulmonary artery seen in PVS is not a feature.

Doppler echocardiography

Noninvasive Doppler studies play a major role in demonstrating the presence, magnitude, and site of the obstruction. They also help find associated cardiac anomalies.

Doppler studies can be very useful in evaluating right ventricle size and function and pulmonary valve anatomy.[6] Note the following:

  • The projections used to obtain these views are the standard and high-parasternal short axis and the subcostal sagittal views. The ventricular cavity and tricuspid valve can also be easily assessed.

  • A subcostal oblique view is especially helpful to visualize hypertrophy of the right ventricle outflow tract (RVOT).

  • Contrast echocardiography may detect the presence of right-to-left shunting at the atrial or ventricular level.

In mild obstruction, cardiac chambers are normal. Their only abnormality may be the hypertrophied infundibulum with a turbulent flow across it. High flow velocity is confirmed with pulsed wave and continuous wave Doppler studies.

In moderate-to-severe obstruction, the right ventricle is dilated and hypertrophied, and the right atrium may also be dilated, with the atrial septum bulging toward the left atrium. In cases of dynamic obstruction that characterize the infundibular hypertrophy, a late-peaking Doppler signal is recorded across the RVOT.

Doppler studies can be used to quantify the pressure drop across the stenosed infundibulum. The peak velocity measured across the RVOT is used to calculate the pressure gradient, using the modified Bernoulli equation, p = 4V2 (p is the peak instantaneous pressure gradient in mm Hg across the obstructed infundibulum, whereas V is peak flow velocity in m/sec distal to the obstructive orifice). Note the following:

  • The technique is as accurate as cardiac catheter data in prediction of pressure gradients across the RVOT.

  • Doppler studies measure the actual instantaneous pressure gradient, which is about 10% more than the peak-to-peak gradient measured using cardiac catheterization.[7]

Do not allow for possible energy losses caused by the elongated obstruction or the presence of narrowing at more than a single level in patients with infundibular obstruction.

Transesophageal echocardiography

Transesophageal echocardiography is more widely used for the diagnosis and more important during interventions, including surgical correction.

Electrocardiography

Electrocardiographic findings may include the following:

  • With mild stenosis, ECG findings are usually within reference ranges. Occasionally, a rightward shift of the main QRS frontal axis may be present.

  • Moderate-to-severe cases show right-axis deviation and right ventricle hypertrophy, proportional to severity.

  • Except in the newborn period, the height of the R wave in right chest leads provides an assessment of the right ventricle pressure.

  • Upright T waves and QRS in right chest leads and incomplete right bundle-branch block may be present but do not necessarily indicate severity of obstruction. Tall p waves suggest right atrial enlargement (p pulmonale).

  • In infants with maximal obstruction bordering on pulmonary atresia, the evidence for right ventricle hypertrophy may be less convincing, and left ventricle dominance is rarely observed.

  • The abrupt transition in the pattern of the QRS complex in the mid-precordial leads, a pattern often found with tetralogy of Fallot, is not seen.

Procedures

Cardiac catheterization

Cardiac catheterization is not essential for diagnosis or to assess severity. The procedure is sometimes undertaken before surgical intervention and in infants for whom other associated lesions must be evaluated. Occasional reports of balloon dilatation of RVOT are available, but results are not encouraging. The procedure is not recommended in patients with infundibular pulmonary stenosis (IPS).

Resting peak systolic pressures in the right ventricle of more than 30-35 mm Hg, as well as pressure gradients across the stenotic infundibulum of more than 10-15 mm Hg, are considered abnormal.

In mild IPS, pulmonary artery pressure is normal. In severe IPS, a marked reduction of mean pulmonary artery pressure and obliteration of the usual pulsatile configuration of the pressure tracing are present.

The presence of IPS may be suggested by the withdrawal pressure tracing. In some cases of combined valvar and discrete infundibular stenosis, two pressure gradients may be encountered; the first at the valve and the second at the infundibular level. Note the following:

  • Pressure gradients may be encountered at more than one level, making it difficult to assess the severity of all but the most proximal stenoses.

  • In severe valvar stenosis with diffuse infundibular narrowing, a characteristic infundibular pressure pulse pattern is frequently observed.

  • End-diastolic pressure in the right ventricle may be normal or elevated with severe obstruction or right ventricle failure.

The degree of right ventricle hypertension is the main indicator of severity. Mild stenosis is present when the proximal systolic pressure is less than 60 mm Hg. With moderate stenosis, this pressure may be as high as 100 mm Hg; above this level, the stenosis is considered severe. Other hemodynamic findings in severe stenosis include the following:

  • Right ventricle end-diastolic and right atrial a wave pressures are elevated.

  • A high v wave in the right atrium indicates tricuspid regurgitation.

  • A right-to-left shunt at the atrial or ventricular level should be sought in all patients with cyanosis.

  • A left heart catheterization is indicated in all patients with subvalvular stenosis that may be a component of a hypertrophic cardiomyopathy.

Angiocardiography

The following features may be noted on angiography:

  • Right ventriculography in right anterior oblique projection demonstrates obstruction at the infundibular level.

  • The best all-purpose projection for evaluation of the pulmonary outflow tract and pulmonary arteries is an anteroposterior projection with a 45° head-up tilt.

  • When taken along with the lateral projection, a good view is obtained of all the important structures.

  • This projection makes distinguishing the hourglass variant from bottle-shaped sinuses possible.

  • A 4-chamber axial oblique projection may occasionally be preferred to visualize the pulmonary artery bifurcation.

Left-sided angiocardiography is indicated when a ventricular septal defect or a left-sided obstruction is present. The long-axis oblique projection is the most useful and is the best tool to accurately diagnose this lesion. Note the following:

  • Always perform biplane angiocardiography when evidence of a significant intraventricular pressure gradient has been found during cardiac catheterization.

  • Anterior projections reveal filling defects within the right ventricle between the outflow and inflow areas.

Histologic Findings

Isolated infundibular stenosis of the pulmonary artery is a mass of muscle-fibrous tissue that creates an obstacle to blood flow in the right ventricle.

Morphogenetic regularities of compensatory and adaptive reactions in isolated infundibular stenosis are similar to those in hypertrophic cardiomyopathy.

Some investigators have suggested that abnormalities in the structure of the hypertrophied myocardium in isolated stenosis of the right ventricle infundibulum are caused by a fundamental error in the cardiac morphogenesis and do not reflect an increased degree of cardiac hypertrophy.

 

Treatment

Medical Care

The primary function of medical management is to assess the severity and progression of stenosis. Note the following:

  • A decision must be made as to when the gradient is sufficiently severe to warrant relieving the obstruction.

  • Careful follow-up is necessary for children younger than 12 years because changes in the severity of their conditions are not uncommon.

  • Follow-up is conducted almost wholly by Doppler studies.

  • If diagnostic questions arise after careful Doppler echocardiographic evaluation, cardiac catheterization and angiography are sometimes performed before surgical intervention. However, transesophageal echocardiogram and magnetic resonance imaging have largely replaced the role of diagnostic catheterization in these patients.[8]

  • The main indicators of progression are the degree of right ventricular hypertrophy on ECG and echocardiography and the peak and mean systolic pressure gradients across the pulmonary outflow. Onset of symptoms (eg, hypoxic spells, angina, signs of congestive heart failure, radiological evidence of cardiomegaly) also influences the decision to surgically intervene.

  • Heart failure therapy is indicated only as a temporary measure in patients with heart failure. Supervise heart failure therapy closely to look for signs of worsening. Ensure adequate hydration and, if necessary, use beta-adrenergic blockers to relax the infundibular muscles.[9]

  • Balloon dilatation and stenting of the right ventricular outflow tract can be considered in babies with significant infundibular pulmonary stenosis (IPS).[10]

  • Prior to intervention, administration of alprostadil minimizes cyanosis in neonates with ductal-dependent pulmonary blood flow.

Transfer

When age appropriate, transfer the patient to a cardiologist specializing in adults.

Subsequent hospitalization is required only for cardiac catheter studies, when indicated, or for surgical intervention.

Diet and activity

The severity of malnutrition determines dietary requirements.

No activity restrictions are necessary for patients with mild-to-moderate stenosis. Allow patients to limit their own activity, based on personal tolerance.

Avoid dehydration at all costs.

Surgical Care

In general, surgical interventions for patients with infundibular pulmonary stenosis (IPS) include the following:

  • Corrective surgery, specifically resection of the hypertrophied infundibulum and enlargement of outflow tract with patch, if required

  • Conduit repair of outflow for severe cases in infancy (Some have achieved good results using a conduit to bypass the obstructed outflow segment.)

  • Insertion of a Blalock-Taussig shunt (used only for infants with an inoperable lesion or in cases in which surgical skills are not available)

Indications for surgical intervention include the following:

  • Presence of such symptoms as shortness of breath, cyanosis, chest pain

  • Severe stenosis with gradients exceeding 100 mm Hg, even if the patient is asymptomatic

  • Severe cyanosis or heart failure in infancy

Consultations

Consider consultations with the following specialists:

  • Pediatric cardiologist

  • Radiologist

  • Family physician

  • Occupational therapist

  • Physiotherapist

  • Psychologist

  • Pharmacist

  • Dietitian

 

Medication

Medication Summary

Surgery is the mainstay of treatment for significant stenosis. Antibiotics for endocarditis prophylaxis are given to patients with infundibular pulmonary stenosis (IPS) before performing procedures that may cause bacteremia. Endocarditis prophylaxis is recommended throughout life, even after surgical relief. For more information, see Antibiotic Prophylactic Regimens for Endocarditis. Heart failure therapy is indicated only as a temporary measure for patients with heart failure. Ensure adequate hydration before administering diuretics because the cardiac output depends on adequate preload; if necessary, use beta-adrenergic blockers to relax the infundibular muscles. Alprostadil minimizes cyanosis in neonates with ductal-dependent pulmonary circulation.

Beta-adrenergic blocking agents

Class Summary

These agents inhibit beta1- and beta2-adrenergic receptors. They inhibit chronotropic, inotropic and vasodilatory responses to beta-adrenergic stimulation. Their exact mechanism of benefit is uncertain, although it is believed to relieve infundibular spasm.

Propranolol (Inderal)

Inhibits beta1- and beta2-adrenergic receptors.

Diuretics

Class Summary

These agents are used to eliminate retained fluid and lower preload. They promote excretion of water and electrolytes by the kidneys. They are used to treat heart failure or hepatic, renal, or pulmonary disease when sodium and water retention has resulted in edema or ascites.

Furosemide (Lasix)

Increases water excretion by interfering with Cl-binding cotransport system, which, in turn, inhibits NA and Cl reabsorption in ascending Henle loop and distal renal tubule. When administered IV, also has a venodilation action; thus lowering the preload even before diuresis sets in. DOC for acute heart failure and for exacerbations of chronic heart failure; used for long-term management of chronic heart failure.

Spironolactone (Aldactone)

Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions.

Amiloride (Midamor)

Potassium-sparing diuretic acting directly on the distal renal tubule. Often combined with a nonsparing-potassium diuretic.

Prostaglandins

Class Summary

These agents are used to maintain patency of ductus arteriosus in patients with duct-dependent circulation.

Alprostadil IV (Prostin VR Pediatric)

Acts on the smooth muscles of the ductus arteriosus and prevents its closure in response to elevation of arterial oxygen saturation. First-line medication used as palliative therapy to temporarily maintain patency of the ductus arteriosus prior to surgery. Beneficial in infants with congenital defects that restrict pulmonary or systemic blood flow and who depend on a patent ductus arteriosus to get adequate oxygenation and lower body perfusion. Produces vasodilation and increases cardiac output. Each 1-mL ampule contains 500 mcg/mL. Used to maintain patency of ductus arteriosus when cyanotic lesion (critical pulmonary stenosis/atresia) or interrupted aortic arch presents in newborns.