Right Ventricular Metabolic Adaptation to Afterload and Heterogeneous RV-Pulmonary Arterial Coupling in Pre-Capillary Pulmonary Hypertension: An FDG-PET/CMR Study

BACKGROUND Right ventricular (RV) failure is the primary determinant of prognosis in pulmonary hypertension (PH) and is associated with metabolic remodeling. However, the relationship between RV metabolic activity, pulmonary vascular load, and RV-pulmonary arterial (RV-PA) coupling remains incompletely understood. We hypothesized that increased pulmonary vascular afterload is associated with enhanced RV glucose metabolism and impaired RV-PA coupling, reflecting early maladaptive RV adaptation before overt structural remodeling develops. This study investigated the interplay among pulmonary vascular resistance (PVR), RV structure, RV-PA coupling, and RV myocardial glucose metabolism using integrated cardiac magnetic resonance (CMR) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS Fifty patients with pre-capillary PH underwent CMR and FDG-PET. Ventricular volumes were quantified by CMR, and RV-PA coupling was estimated using the stroke volume to end-systolic volume ratio (SV/ESV). RV metabolic activity was quantified using standardized uptake value (SUV). Associations among PVR, RV structure, RV-PA coupling, and RV metabolic activity were analyzed. RESULTS PVR was positively correlated with SUV RV (r = 0.452, P < 0.001), indicating increased RV glucose uptake with higher afterload. PVR was inversely correlated with SV/ESV (r = -0.282, P = 0.048), indicating impaired RV-PA coupling. Right ventricular end-diastolic volume index (RVEDVI) showed a modest association with SUV RV (r = 0.273, P = 0.055) and was not significantly correlated with SV/ESV (r = -0.197, P = 0.170). These findings indicate that RV metabolic remodeling is more closely associated with pulmonary vascular afterload and RV-PA uncoupling than with overt RV dilatation. CONCLUSIONS RV glucose metabolism is significantly associated with pulmonary vascular load and impaired RV-PA coupling, potentially reflecting early maladaptive adaptation to increased afterload preceding overt structural remodeling. Integrated FDG-PET and CMR assessment provides complementary mechanistic insight into RV adaptation in PH.