View Abstract

A4375 - EIPAH and PAH Subjects Have Different Regional Perfusion Patterns After Vasodilation
Author Block: P. Kohli1, T. Winkler2, V. J. Kelly3, E. Gladysheva4, M. Kone1, K. Hibbert5, J. M. Rodriguez-Lopez6, J. G. Venegas7, R. N. Channick8, R. Harris7; 1Pulmonary and Critical Care Medicine, Massachsuetts General Hospital, Boston, MA, United States, 2Dept of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospiital and Harvard Medical School, Boston, MA, United States, 3inviCRO, Boston, MA, United States, 4Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, United States, 5Pulmonary/Critical Care, Harvard, Boston, MA, United States, 6Medicine, Mass General Hospital, Boston, MA, United States, 7Massachusetts General Hosp, Boston, MA, United States, 8Massachusetts General Hospital, Boston, MA, United States.
RATIONALE: It is unknown whether exercise-induced pulmonary arterial hypertension (EIPAH) is a distinct disease entity from pulmonary arterial hypertension (PAH) or whether it exists along a spectrum of pulmonary vascular resistance. We aimed to investigate the resting supine regional pulmonary perfusion patterns in these conditions using PET-CT functional imaging with the hypothesis that EIPAH would have an intermediate vascular phenotype.
METHODS: To date, 4 healthy controls (HC), 2 EIPAH and 3 PAH subjects have completed the study. Subjects performed high-resolution computed tomography (HRCT) followed by bolus 13NN-saline functional imaging of pulmonary perfusion at baseline and after breathing inhaled Nitric Oxide, (iNO+O2.) The vertical gradient of perfusion (QVgrad) was determined before and during vasodilation. Heterogeneity of perfusion was quantified as noise-free coefficient of variation (CV2). The contribution of the gradients in the vertical and axial directions to CV2 were then removed. Finally, the contribution of different length scales to perfusion heterogeneity was assessed by computing CV2 of low-pass-filtered images (filter sizes: 10, 30, 50, 70, 90 and 110 mm), and calculating the difference in CV2 between successive filter sizes.
RESULTS: There were no differences in Qvgrad or perfusion heterogeneity prior to vasodilation. However, after vasodilation, there was a clear separation in Qvgrad between PAH subjects with an average Qvgrad 3.5 %/cm compared to EIPAH 7.0 %/cm or HC 7.3 %/cm. The HC and EIPAH subjects demonstrated a consistent increase in the Qvgrad following iNO+O2 administration (27% and 19%, respectively), compared with virtually no change (2.6%) in PAH patients. Total CV2 was lowest in PAH subjects after vasodilation compared to EIPAH and HC (0.051 versus 0.19 and 0.12, respectively). After removal of
the contribution of Qvgrad, EIPAH subjects had increased perfusion heterogeneity at all length scales after vasodilation.
CONCLUSIONS: We have strong preliminary evidence that PAH patients in the supine position have a reduction in the Qvgrad for perfusion that does not change with vasodilation. EIPAH subjects, on the other hand, retain a Qvgrad similar to HC. However, EIPAH patients after vasodilation demonstrated greater CV2 of perfusion at all length scales compared with HC and PAH subjects. This may indicate a more heterogeneous disease process in EIPAH than in PAH. In conclusion, PET-CT functional imaging of regional pulmonary perfusion and blood flow dynamics can differentiate PAH patients from HC and EIPAH and may indicate distinct vascular pathology in EIPAH.
SPONSER: United Therapeutics