Clinical Outcomes and Activation of Circulating Endothelial Progenitor Cells Following Application of ASD Occluder in Patients with Flow-Induced Pulmonary Hypertension

Abstract

Purpose The presence of left-to-right shunt atrial septal defect (ASD) may result in pulmonary hypertension. Most secundum type ASDs are amenable to close by the Amplatzer device and pulmonary artery pressure (PAP) is known to change following closure of ASD. Altered blood flow is known to activate vascular endothelial cells and their progenitors, namely endothelial progenitor cells (EPCs). In this study, we investigated the biological changes in circulating EPCs following application of ASD occluder and the functional improvement in patients with excessive pulmonary blood flow. Methods and Materials Successive patients with the age ranging from 18 to 60 years admitted for transcatheter closure of ASD using the Ampaltzer occluder were included in this study. Blood samples were collected immediately before application of occluder and 20 minutes after successful occlusion of blood flow in the ASD. Mononuclear cells were isolated from the peripheral blood, and numbers and outgrowth colony formation of EPCs were determined. Transthoracic echocardiography, blood tests and functional evaluation were repeated one month later. Results Compared with baselines, significantly higher numbers of EPC outgrowth colonies were observed from the blood samples collected after successful application of ASD occluder and cessation of the left-to-right shunt. Closure of ASD reduced PAP and serum BNP levels. Moreover, daily performance of patients also improved following reduction of pulmonary arterial blood flow. Conclusions Our preliminary results demonstrate that occlusion of ASD reduces PAP and improves physiological status of patients with flow-induced pulmonary hypertension. Application of ASD occluder and restoration of normal pulmonary blood flow significantly enhance EPC outgrowth colony formation in the in vitro environment. The biological regulation and clinical relevance of EPCs in flow-induced pulmonary hypertension is in need of further investigation.