Congenital Supravalvular Pulmonary Stenosis

Congenital supravalvular pulmonary stenosis is narrowing of the main pulmonary artery distal to the pulmonary valve, at the sinotubular junction, along the trunk, or at the bifurcation, often extending into the branch arteries. It raises right ventricular pressure and can cause right ventricular hypertrophy and failure.

It is uncommon. Pulmonary valve stenosis forms 8 to 12% of congenital heart disease, while supravalvular and peripheral pulmonary stenosis together form well under 5%.

It is associated with Williams syndrome, Alagille syndrome (JAG1 variants), Noonan syndrome, congenital rubella, cutis laxa, Keutel syndrome and Ehlers-Danlos syndrome. It can also occur after pulmonary artery banding, and as an isolated familial condition.

Mild narrowing seldom progresses and is well tolerated. Severe narrowing needs mechanical relief to prevent right ventricular failure.

Pathophysiology.

Abnormal elastin or vessel wall development produces a fibrous ridge or segmental hypoplasia of the pulmonary arterial wall. The right ventricle develops concentric hypertrophy to maintain flow.

Right ventricular systolic pressure rises in proportion to the gradient. Persistent high pressure with hypertrophy causes diastolic dysfunction, tricuspid regurgitation, arrhythmia, and late failure. When the stenosis extends to the branches, flow is unevenly distributed and some lung segments are overperfused.

Grading by right ventricular pressure: mild under 50 mmHg (peak gradient under 36 mmHg), moderate 50 to 79 mmHg, severe 80 mmHg or more (or more than two thirds of systemic pressure).

Mild disease is asymptomatic. Moderate to severe disease produces exertional dyspnoea, fatigue, exercise intolerance, chest pain, syncope and right heart failure. Cyanosis appears when right-to-left shunting occurs across an atrial septal defect or foramen ovale.

Signs are a systolic ejection murmur at the upper left sternal edge radiating to the back and axillae (unlike valvular stenosis, there is no ejection click), a right ventricular heave and signs of right heart failure. Look for features of the underlying syndrome (dysmorphism, cholestasis, rubella stigmata).

• Echocardiography: site and length of narrowing, peak Doppler gradient, right ventricular hypertrophy, tricuspid regurgitation velocity and right ventricular systolic pressure, pulmonary valve appearance (normal in this lesion), branch artery size, atrial septal communication and flow patterns. Distal branches are hard to image.
• CT angiography or cardiac MRI define the anatomy of the pulmonary tree, vessel diameters and lung perfusion asymmetry. Lung perfusion scan quantifies differential flow.
• Catheterisation: right ventricular pressure, gradients across each lesion and angiography. Used before intervention.
• Genetic tests: microarray for 7q11.23 deletion (Williams), JAG1 sequencing (Alagille), RASopathy panel (Noonan). Maternal rubella history.
• ECG: right ventricular hypertrophy and right axis deviation.

Differential diagnosis.

• Valvular pulmonary stenosis and subvalvular right ventricular outflow obstruction.
• Physiological branch stenosis of the newborn (resolves by 3 to 6 months).
• Tetralogy of Fallot, pulmonary artery sling and extrinsic compression (mediastinal mass, fibrosing mediastinitis).
• Pulmonary arteritis (Takayasu) and post-surgical stenosis.

Mild disease (right ventricular systolic pressure under 50 mmHg, no symptoms): observation with echocardiography every 1 to 3 years. Physiological newborn flow murmur resolves.

Indications for intervention. Right ventricular systolic pressure over 50 mmHg, or over half of systemic pressure with a diameter reduction of more than 50%; right ventricular dysfunction or hypertrophy with symptoms; or marked flow asymmetry (one lung receiving under 35% of total perfusion).

Interventions.

• Balloon angioplasty with a high pressure non-compliant balloon (balloon to vessel diameter ratio 1.0 to 1.5, inflated to the rated burst pressure) with or without a cutting balloon. Success (more than 50% fall in gradient) is limited for elastin arteriopathy because of recoil.
• Stent placement (large premounted stents, dilatable to adult size) gives more durable relief in the main pulmonary artery and proximal branches. Complications are vessel rupture or aneurysm (1 to 2%), reperfusion pulmonary oedema in a segment that regains flow, and stent fracture.
• Surgical patch augmentation of the pulmonary trunk and branches for lesions unsuitable for stents, or when other surgery is needed.
• Heparin 100 units/kg intravenously during catheterisation (activated clotting time over 200 seconds); cefazolin 1 g intravenously (children 25 mg/kg, maximum 1 g) before stenting.
• After stenting: aspirin 3 to 5 mg/kg orally daily (adults 75 to 100 mg) for 6 months, and longer by specialist decision.
• Reperfusion oedema: oxygen, furosemide 1 mg/kg intravenously (adults 40 mg), and ventilatory support if needed.

Right ventricular failure (late): furosemide 20 to 40 mg orally daily (children 1 mg/kg every 12 hours, maximum 6 mg/kg daily) with spironolactone 25 to 50 mg daily (potassium under 5.0 mmol/L and eGFR over 30 mL/min/1.73 m2; check at 1 and 4 weeks). Electrolytes and creatinine within 1 week of changes.

Endocarditis prophylaxis. Only with prosthetic material in the first 6 months after stenting or surgery, and lifelong after previous endocarditis: amoxicillin 2 g orally (children 50 mg/kg, maximum 2 g) 30 to 60 minutes before dental procedures.

Underlying conditions. Williams syndrome: monitor for aortic and renal artery stenosis and hypercalcaemia. Alagille syndrome: hepatic and renal assessment. Rubella: prevention by vaccination before pregnancy (not during pregnancy).

Monitoring. Echocardiography at 6 and 12 months after intervention, then every 1 to 2 years. CT or MRI surveillance for stent and vessel integrity every 3 to 5 years. ECG yearly.

Referral and escalation. Refer every confirmed case with a significant gradient to a paediatric or adult congenital heart service. Urgent referral for cyanosis, syncope, right heart failure or after intervention complications.

Special groups.

• Pregnancy: tolerated when right ventricular pressure is under half of systemic pressure and function is normal; severe stenosis raises risk of right heart failure, so intervene before conception.
• Children: early catheter intervention is often more effective, with re-dilatation as the child grows.
• Williams syndrome: anaesthesia and sedation carry a high risk of cardiac arrest, so assess coronary and outflow lesions first.
• Region specific: congenital rubella remains a cause where vaccination coverage is low.