Pulmonary Venous Obstruction in Congenital Heart Disease

Lay Summary: Our research program is looking a pulmonary vein stenosis. This is a condition where the veins between the heart and the lungs get narrowed. Sometimes babies are born with this problem. More commonly, the problem develops after a surgical repair of the veins. In either setting, the problems is very difficult to treat and often fatal. Although we have developed surgical procedures which can ‘unblock’ the portion of the pulmonary veins near the heart, we have no therapy available for pulmonary veins which are narrowed in the ‘upstream’ portions of the lungs. When patients get diffuse upstream pulmonary vein stenosis, they almost invariably die.

Using funding from the Saving tiny Hearts Society, we developed a model in piglets which recreates the upstream disease and allows us to study it. Based on analysis of the tissues, we hypothesized that losartan (a commonly prescribed drug) would help to slow progression of upstream pulmonary vein stenosis in our model. The drug had a very favorable effect and our data was recently accepted for publication. We need to do more confirmatory studies in piglets and some mechanistic studies in a mouse model to generate sufficient evidence to support a properly designed clinical trial. Our work is exciting because this preliminary data is the first demonstration that a drug (or any therapy) can be used to treat upstream pulmonary veinstenosis.