An autopsy case of pulmonary veno-occlusive disease refractory to imatinib

To the Editors: Pulmonary veno-occlusive disease (PVOD) is a rare variant of pulmonary hypertension (PH). PVOD is reportedly refractory to the majority of PH-specific vasodilators; however, a recent case report demonstrated that a tyrosine kinase inhibitor, imatinib, markedly improved functional capacity in a patient with PVOD 1. The present case report documents clinical and haemodynamic effects of imatinib in a patient with pathologically confirmed PVOD. In 2007, a 73-yr-old female experienced progressive exertional dyspnoea and was diagnosed with PH in a community hospital. Diuretics and beraprost (oral prostanoid) were administered to no avail. The patient was referred to Hokkaido University Hospital (Sapporo, Japan) in November 2008. She had never smoked and had no occupational or environmental inhalation history. Functional capacity was New York Heart Association class III. Blood pressure was 110/65 mmHg, and coarse crackles were present in both lungs. Serum aspartate aminotransferase and alanine aminotransferase levels were within normal range, whereas hepatitis B (HB) surface and HBe antigens were both positive. Serum brain-type natriuretic polypeptide was elevated at 2,456 pg·mL−1, and arterial blood gas analysis showed hypoxaemia (arterial oxygen tension 55.2 mmHg) and hypocapnia (arterial carbon dioxide tension 33.9 mmHg). Chest radiography demonstrated marked cardiomegaly, dilated main pulmonary artery and pulmonary congestion. Echocardiography showed marked right atrial and ventricular enlargement and severe tricuspid regurgitation. Pulmonary function tests revealed normal forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FEV1/FVC, whereas diffusing capacity of the lung for carbon monoxide ( D L,CO) and D L,CO/alveolar volume ( V A) were markedly reduced: D L,CO 4.16 mL·min−1·mmHg−1, 33.5% of predicted; D L,CO/ V A 1.61 mL·min−1·mmHg−1·L−1, 37.4% pred. High-resolution computed tomography (HRCT) revealed slight …