Endothelial NO-Synthase Gene-Enhanced Progenitor Cell Therapy for Pulmonary Arterial Hypertension The PHACeT Trial

were delivered into the right atrium via a multiport pulmonary artery catheter during continuous hemodynamic monitoring in an intensive care unit setting. Seven patients (5 women) received treatment from December 2006 to March 2010. Cell infusion was well tolerated, with no evidence of short-term hemodynamic deterioration; rather, there was a trend toward improvement in total pulmonary resistance during the 3-day delivery period. However, there was 1 serious adverse event (death) which occurred immediately after discharge in a patient with severe, end stage disease. Although there were no sustained hemodynamic improvements at 3 months, 6-minute walk distance was significantly increased at 1, 3, and 6 months. Conclusion: Delivery of endothelial progenitor cells overexpressing endothelial nitric oxide synthase was tolerated hemodynamically in patients with PAH. Furthermore, there was evidence of short-term hemodynamic improvement, associated with long-term benefits in functional and quality of life assessments. However, future studies are needed to further establish the efficacy of this therapy. general linear regression analyses of outcomes measured repeatedly over time, after making normalizing transformations where necessary and visually verifying that normality assumptions were reason- able. In the general linear regression analyses, time was modeled using a fixed categorical covariate, and regression parameters were estimated using restricted maximum likelihood estimation with de-grees of freedom estimated using the Kenward–Roger method as recommended for small samples. 31 The variance–covariance ma-trix was modeled to account for correlation in repeated measures on the same patient over time. Analyses were conducted using all available data on each patient. To examine the potential impact of missing data, sensitivity analyses were conducted using single impu-tation under conservative assumptions about the missing responses. Analyses were conducted using the Mixed procedure in SAS v.9. 2 32 and GraphPad Prism (version 5 for Mac, GraphPad Software, La Jolla, CA, www.graphpad.com). might represent a promising new therapy for this disease. The Pulmonary Hypertension and Angiogenic Cell Therapy (PHACeT) trial is the first clinical pulmonary hypertension study to use genetically enhanced EPCs, which are designed to repair and regenerate blood vessels. This study shows that gene-enhanced EPCs can be given to the lung circulation of patients with PAH without immediate adverse hemodynamic effects. One patient with severe pulmonary hypertension died shortly after hospital discharge. Patients with advanced disease and indications of high risk may not be suitable for this therapy. In most patients, there was a modest short-term improvement in pulmonary arterial pressure. There were significant and persistent benefits in the mean walking distance and quality of life scores for ≤ 6 months. This study suggests feasibility of ad-ministering genetically modified endothelial nitric oxide synthase to patients with severe PAH without immediate adverse hemodynamic effects. Future clinical trials are needed to support the use of this innovative approach in restoring functional lung blood vessels, as a potential transformative therapy, in patients with PAH.