Congenital Pulmonary Vein Anomaly

Congenital pulmonary vein anomalies are malformations in which the pulmonary veins connect abnormally to the right side of the heart or to the systemic veins, or are narrowed from birth. The main entities are total anomalous pulmonary venous connection, partial anomalous pulmonary venous connection (including scimitar syndrome), congenital pulmonary vein stenosis, and cor triatriatum sinister. This article covers the spectrum and chooses the disease type for each entity.

Total anomalous pulmonary venous connection occurs in about 1 in 15,000 live births (1 to 3% of congenital heart disease). All four veins drain to the right atrium or a systemic vein, and survival needs an atrial septal communication. Types are supracardiac (about 45%, through a vertical vein to the innominate vein or superior vena cava), cardiac (about 25%, to the coronary sinus or right atrium), infracardiac (about 25%, descending through the diaphragm to drain into the portal system) and mixed (about 5%).

Partial anomalous connection involves one to three veins. It is found in about 0.4 to 0.7% of the population in autopsy series, and it is often accompanied by a sinus venosus defect. Scimitar syndrome (right pulmonary veins draining to the inferior vena cava, with right lung hypoplasia, dextroposition and systemic arterial supply from the aorta) is rare.

Obstruction occurs in nearly all infracardiac cases and in some others. It is a surgical emergency. Heterotaxy with asplenia is a frequent association.

Pathophysiology.

In total anomalous connection, pulmonary and systemic venous return mix in the right atrium. The right ventricle receives the whole venous return, and blood reaches the left heart through the atrial septal defect. Saturation depends on the pulmonary to systemic flow ratio.

When the venous channel is obstructed, pulmonary venous pressure rises, causing severe pulmonary oedema, pulmonary hypertension, hypoxaemia and acidosis with a small left heart. Without obstruction, heart failure develops from pulmonary overcirculation.

In partial connection, the shunt overloads the right heart in proportion to the number of veins involved. Scimitar syndrome adds lung hypoplasia and pulmonary hypertension in infancy.

Congenital pulmonary vein stenosis arises from intimal fibroproliferation by myofibroblast like cells. It progresses and extends upstream into the lung, and recurs after intervention.

• Obstructed total anomalous connection: severe cyanosis, tachypnoea and respiratory distress in the first days of life, a quiet precordium without murmur, and shock.
• Unobstructed total anomalous connection: mild cyanosis, tachypnoea, poor feeding, failure to thrive, recurrent respiratory infection, a right ventricular heave, wide split second heart sound and a flow murmur.
• Partial connection: often asymptomatic, with later exertional dyspnoea, right heart dilatation and arrhythmia. Scimitar syndrome presents in infancy with heart failure and pulmonary hypertension, or in adults with recurrent infection.
• Pulmonary vein stenosis: tachypnoea, wheeze, recurrent infection, haemoptysis, pulmonary hypertension and failure to thrive.

• Foetal and postnatal echocardiography: abnormal veins and confluence, vertical vein or descending vein, atrial septal communication, right heart dilatation, small left atrium, flow acceleration (continuous flow over 1.6 m/s with loss of phasic variation suggests obstruction), and pulmonary pressure.
• Chest radiograph: snowman (supracardiac type), small heart with diffuse ground glass pulmonary oedema (obstructed infracardiac type), or scimitar vein sign.
• CT angiography or cardiac MRI define the pulmonary veins, confluence, systemic arterial supply to the right lung, lung hypoplasia and associated anomalies. Catheterisation is reserved for pulmonary vein stenosis (pressure gradients and intervention) and haemodynamic uncertainty.
• Arterial blood gas and lactate in the neonate. Genetic testing and screening for heterotaxy features.

Differential diagnosis.

• Persistent pulmonary hypertension of the newborn and respiratory distress syndrome.
• Cor triatriatum, mitral stenosis and other causes of pulmonary venous obstruction.
• Transposition of the great arteries and other cyanotic lesions.
• Secundum and sinus venosus atrial septal defects, and primary pulmonary vein stenosis.

Obstructed total anomalous connection (emergency).

• Intubate and ventilate with positive end expiratory pressure to reduce pulmonary oedema. Correct acidosis with ventilation and sodium bicarbonate 1 to 2 mmol/kg intravenously over 30 minutes when pH is under 7.1.
• Support circulation with dopamine 5 to 10 microgram/kg/min or adrenaline 0.05 to 0.3 microgram/kg/min. Give volume cautiously (10 mL/kg) only if hypovolaemic.
• Avoid alprostadil unless the diagnosis is uncertain or there is a critical right-to-left ductal need, since it increases pulmonary flow and worsens oedema.
• Early surgical repair within hours to days: anastomose the pulmonary venous confluence to the left atrium, ligate the vertical vein, and close the atrial septal defect. Extracorporeal membrane oxygenation is used as a bridge in profound instability. Survival is about 85 to 95% in experienced centres.

Unobstructed total anomalous connection. Surgical repair within the first weeks to months of life (earlier with heart failure). Furosemide 1 mg/kg orally every 12 hours (maximum 6 mg/kg daily; electrolytes and creatinine at 1 week) until repair.

After repair. Pulmonary hypertensive crisis in the first 48 to 72 hours: inhaled nitric oxide 20 ppm (range 5 to 40 ppm; monitor methaemoglobin, wean slowly), sedation and analgesia with fentanyl 1 to 5 microgram/kg/h infusion, and controlled ventilation with PaCO2 of 35 to 40 mmHg and normal pH. Pulmonary vein stenosis develops in about 5 to 15% of repaired cases, usually in the first 6 months, so surveillance is essential.

Partial connection.

• Single anomalous vein with no right ventricular dilatation: no treatment, and observation by echocardiography every 2 to 3 years.
• Surgical redirection (baffle, vein reimplantation, or Warden type operation) when the pulmonary to systemic flow ratio is 1.5 or more with right ventricular volume overload, with pulmonary vascular resistance under 3 Wood units.
• Scimitar syndrome: repair of the anomalous drainage when the flow ratio is 1.5 or more, with coil embolisation of aortopulmonary collaterals. Infants with pulmonary hypertension and hypoplastic lung have a poor outcome and need specialist treatment (diuretics, pulmonary vasodilator therapy, and sometimes pneumonectomy).

Congenital pulmonary vein stenosis.

• Catheter balloon angioplasty and stenting, sutureless surgical repair, and repeated intervention. Restenosis is common. Bilateral and multi-vessel disease has high mortality.
• Antiproliferative drug therapy (sirolimus by mouth, adjusted to a trough of 5 to 15 ng/mL, or chemotherapy such as vinblastine and methotrexate) is used in specialist centres with limited evidence. Monitor trough levels, lipids, infection and wound healing with sirolimus.
• Pulmonary hypertension treatment: sildenafil and bosentan by specialist paediatric pulmonary hypertension teams.

Prevention.

• RSV prevention in infants under 2 years: palivizumab 15 mg/kg intramuscularly monthly in season (up to 5 doses), or nirsevimab single dose by weight (50 mg under 5 kg, 100 mg for 5 kg or more) where available.
• Endocarditis prophylaxis when prosthetic material is present or after previous endocarditis: amoxicillin 50 mg/kg (maximum 2 g) orally 30 to 60 minutes before dental procedures.

Monitoring. Echocardiography at discharge, 1, 3, 6 and 12 months after repair, then yearly for 5 years and every 1 to 2 years afterwards, with CT or MRI for suspected stenosis. Pulmonary vein gradient over 2 mmHg mean on Doppler suggests obstruction. ECG and ambulatory ECG for arrhythmia.

Referral and escalation. Refer every suspected case to a paediatric cardiac centre at once. Obstructed lesions need transfer for surgery within hours.

Special groups.

• Pregnancy: partial connection with right heart dilatation is usually tolerated; pulmonary hypertension or unrepaired lesions with significant shunt raises risk.
• Heterotaxy: asplenia needs penicillin V prophylaxis (125 mg twice daily under 5 years, 250 mg twice daily from age 5) and vaccination.
• Region specific: late diagnosis of unobstructed lesions is common with limited neonatal screening, and delay allows fixed pulmonary vascular disease.