Pulmonary Vein Stenosis

Pulmonary vein stenosis (PVS) is narrowing of one or more pulmonary veins at the ostium or along the vein, with obstruction to flow into the left atrium. It is congenital (primary), seen in prematurity and chronic lung disease, Down syndrome, and associated heart defects, or acquired.

Acquired causes are repair of total anomalous pulmonary venous connection (post-operative stenosis) and radiofrequency or cryoballoon ablation for atrial fibrillation (now in about 1 to 3% of patients, higher with early techniques and wide ostial ablation).

Other acquired causes are fibrosing mediastinitis (histoplasmosis, tuberculosis, sarcoidosis, IgG4-related disease), radiotherapy, and external compression or invasion by lung or mediastinal tumour.

Severity after ablation is graded by ostial diameter loss: mild under 50%, moderate 50 to 70%, severe over 70%.

Pathophysiology. Primary disease is a progressive intimal proliferation of myofibroblast like cells that narrows the vein and extends distally.

Obstruction raises pulmonary venous pressure in the drained segment, causing pulmonary oedema, and flow redistributes away from the affected lung, which lowers its perfusion and growth. Multiple affected veins cause pulmonary arterial hypertension and right ventricular failure.

Bronchial collaterals form and bleed, causing haemoptysis. Primary disease in infants progresses quickly and recurs after intervention.

• Infants: tachypnoea, recurrent respiratory infections, poor feeding, failure to thrive, pulmonary hypertension and right heart failure.
• Older children and adults: exertional dyspnoea, cough, haemoptysis (can be severe), pleuritic chest pain and recurrent pneumonia in the same lobe, often mistaken for pulmonary embolism or pneumonia. After ablation, symptoms begin 1 to 6 months later. A single stenosed vein may be silent.
• Examination: loud pulmonary second sound, signs of pulmonary hypertension and right heart failure, crackles over the affected lung.

Red flags.

• Haemoptysis
• Progressive pulmonary hypertension
• Two or more veins involved, or bilateral disease
• Recurrent hospital admission in an infant after repair of total anomalous pulmonary venous connection
• New dyspnoea or cough in the months after atrial fibrillation ablation
• Unilateral perfusion loss on a lung scan

• Chest X-ray: segmental pulmonary oedema, Kerley lines, small hemithorax, effusion.
• Echocardiography: pulsed wave Doppler of the veins shows non-phasic turbulent flow with a peak velocity over 1.0 m/s (normal under 1.0 m/s). Also assess right ventricular pressure and function. Transoesophageal echocardiography images the ostia in adults.
• CT pulmonary venography: the key test; ostial diameter, vein length and number involved, lung parenchymal change, and mediastinal disease.
• Cardiac MRI or MR angiography: an alternative, with flow quantification.
• Ventilation perfusion scan: perfusion loss in the affected lung (a perfusion share under 25% for one lung suggests significant stenosis).
• Cardiac catheterisation: pulmonary vein angiography, pulmonary artery pressure, pulmonary vascular resistance and the transvenous gradient; guides intervention.
• Bronchoscopy: for haemoptysis, to exclude an airway source.
• Cause workup: ablation history, mediastinal imaging, tuberculosis and fungal tests, IgG4 and angiotensin converting enzyme levels, tissue diagnosis when a mass is present.

Differential diagnosis.

• Pulmonary embolism and chronic thromboembolic disease
• Pulmonary veno occlusive disease
• Mitral stenosis
• Cor triatriatum
• Left atrial thrombus or myxoma
• Idiopathic pulmonary arterial hypertension
• Bronchiectasis or lung cancer as a cause of haemoptysis
• Bronchopulmonary dysplasia
• Interstitial lung disease
• Scimitar syndrome

• Acquired stenosis after atrial fibrillation ablation: asymptomatic mild or moderate stenosis is observed with imaging. Symptomatic patients, severe stenosis (over 70%) and occlusion with symptoms are treated by balloon angioplasty with stenting, using a stent matched to the reference vein. Restenosis is common and may need repeat dilatation. After stenting, aspirin 75 to 100 mg plus clopidogrel 75 mg orally once daily for 1 to 3 months, then aspirin alone; continue anticoagulation instead when it is already needed for atrial fibrillation or other reasons. Avoid omeprazole and esomeprazole with clopidogrel.
• Primary stenosis in infants and children: catheter angioplasty or drug eluting stenting and surgical sutureless repair, repeated as needed; recurrence is frequent. Antiproliferative therapy (sirolimus, imatinib, bevacizumab, or vinblastine and methotrexate regimens) is used in specialist units, and the evidence is limited. Lung transplantation is the last resort.
• Post-repair stenosis after total anomalous pulmonary venous connection: early re-intervention, because disease progresses.
• Fibrosing mediastinitis and malignancy: treat the underlying cause and relieve obstruction by stenting; immunosuppression is directed by cause in specialist care.
• Congestion: furosemide in adults 40 mg orally once daily in the morning, increased to 80 to 120 mg daily as needed (higher doses in renal impairment under specialist care); monitor sodium, potassium and creatinine. Furosemide in infants and children: 0.5 to 1 mg/kg intravenously every 6 to 12 hours, or 1 to 2 mg/kg orally every 6 to 12 hours, maximum 6 mg/kg daily; monitor sodium, potassium, creatinine and weight.
• Pulmonary vasodilators: can worsen pulmonary oedema while venous obstruction persists. Use only in specialist units.
• Haemoptysis: keep the bleeding side dependent, protect the airway, then bronchial artery embolisation together with relief of venous obstruction.
• Atrial fibrillation: apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Long term.

Special groups. Pregnancy is high risk with severe or multivessel disease and pulmonary hypertension. Relieve the obstruction first.

Monitoring. After intervention: echocardiography, CT or MRI at 1 to 3 months, then at 6 months and yearly, with a perfusion scan when function needs quantifying. In infants with primary disease: echocardiography every 1 to 3 months with catheter reassessment directed by findings. After ablation: CT venography when symptoms start or persist.

Referral and escalation. Refer to a pulmonary hypertension and congenital or electrophysiology centre. Urgent for haemoptysis, rising pulmonary pressure, bilateral or multivessel disease, or any infant with suspected primary disease.