Title: An Evaluation of Right Ventricular Metabolism in Right Heart Failure Associated with Pulmonary Arterial Hypertension
Abstract: Pulmonary arterial hypertension (PAH) results in premature death often as a result of right ventricular (RV) dysfunction. However, there are substantial differences among patients in their tendency to develop RV failure. RV metabolic changes may be able to predict the development of right heart failure in patients with PAH. The purpose of the study was to assess the relationship between right ventricular cardiac metabolism using positron emission scanning (PET) and established parameters related to RV failure including the six minute walk test (6MWT), brain natriuretic peptide (BNP), cardiac index (CI), pulmonary artery pressure, mean right atrial pressure (mean RAP), clinical evidence of RV failure and RVEF. The relationship between PAH specific therapy and cardiac metabolism was also evaluated. Fourteen consecutive patients with a diagnosis of WHO group I PH (PAH) (mean age 56.6 ± 15.5 years) underwent right heart catheterization (RHC) (mPAP 43.3 ± 13.0 mmHg) for assessment of pulmonary hemodynamics and cardiac output (by the Fick method). A total of 86% of patients were on background PAH therapy at the time of enrollment and 43% had a diagnosis of right heart failure. RV glucose and fatty acid metabolism were assessed with (18F) flurodeoxyglucose (FDG) and (18)F-fluoro-6-thioheptadecanoic acid (FTHA) PET scanning respectively. Substrate utilization was reported as a maximum standard uptake value (SUV). Relative RV FDG and FTHA uptake were determined as the ratio of RV/LV SUV. RVEF was determined by cardiac magnetic resonance (CMR). The clinical diagnosis of right heart failure was adjudicated by PH experts blinded to the imaging results. There was a negative correlation between RVEF and RV/LV ratio of FTHA SUV (r=-0.81, p=0.0048) however no correlation was observed between RVEF and that of FDG SUV (r=-0.41, p=0.19). There was a significant positive correlation between mPAP and RV/LV ratio of FDG SUV (r=0.74, p=0.003), and a trend toward an increase in that of FTHA SUV (r=0.56, p=0.06). No significant correlation was shown between both metabolic parameters and 6MWT, BNP, mean RAP as well as CI. Patients with clinical evidence of RV failure had a significant increase in RV FDG uptake (6.63±3.80 vs 3.33±1.73, p<0.05) with a trend towards increased uptake of FTHA (5.53±1.45 vs 3.65±1.67, p=0.06). Patients treated with endothelin receptor antagonists had significantly lower FDG SUV in the RV than that in patients without (3.71±1.72 vs 8.53±4.78, p=0.01), however there was no relationship between RV metabolism and other PAH specific therapy. Clinical right HF is associated with changes in both glucose and fatty acid substrate utilization in the right ventricle. Metabolic changes in the RV may provide incremental prognostic information and could potentially be a treatment target for right HF associated with PAH.