The discrepancy between FDG uptake and myocardial fibrosis in patients with pulmonary arterial hypertension – PET/MRI study
Authors: Kazimierczyk R , Szumowski P , Nekolla S , Malek L A , Blaszczak P , Hladunski M , Sobkowicz B , Mysliwiec J , Kaminski K 
Published: October 2022

Abstract

Background
Inflammatory processes play an important role in pulmonary arterial hypertension (PAH) pathophysiology. We previously confirmed that in case of right ventricle (RV) failure, changes of cytokines' levels are correlated with myocardial metabolic and hemodynamic alterations observed in PET/MRI hybrid imaging. Presence of late gadolinium enhancement (LGE) in RV insertion points (RVIPs) has been found in majority of PAH patients and is often recognized as evidence of myocardial fibrosis due to RV pressure overload. As qualitative and/or quantitative assessments of LGE may vary due to natural PAH progression or specific therapy, we hypothesized that simple presence of LGE at RVIPs is not unequivocal to fibrotic tissue (without metabolic activity).

Purpose
To check the relationship between LGE mass and 18F-fluorodexyglucose uptake in RV insertion points in PAH patients using PET/MRI hybrid imaging.

Methods
Twenty-eight clinically stable PAH patients (49.9±15.9 years) had simultaneous PET/MRI scans during baseline and follow up (FU) visits, Figure. 18F-fluorodexyglucose (FDG) was used as a tracer and its cardiac uptake was presented as a maximum standardized uptake value (SUV) for RV insertion points (SUV in RVIPS). Septal delayed enhancement mass was quantified in RVIPs and presented as LGE mass. Occurrences of clinical end-points (CEP, defined as death or clinical deterioration) were assessed during 24 months observation.

Results
LGE was found in RVIPs of all PAH patients. Mean LGE mass was 6.32±4.41 g and mean SUV in RVIPS was 7.28±5.36. Follow up values were 8.01±7.75g (p=0.4) and 5.80±3.16 (p=0.16), respectively. We observed significant correlation between baseline SUV in RVIPS and mean pulmonary pressure, mPAP (r=0.49, p=0.04) but no correlation was found between LGE mass and SUV in RVIPS (in both baseline and FU scans).
Between baseline and follow up visits, 16 patients had CEP and needed PAH therapy escalation. CEP+ group of PAH patients presented higher baseline LGE mass (7.53±4.75 vs 3.92±2.21, p=0.04) and SUV in RVIPS (7.27±5.42 vs 6.01±4.52, p=0.4). In all CEP patients who initiated prostacycline therapy and survived (n=8, 50%), SUV in RVIPS decreased in FU PET scans together with an increase in LGE mass in MRI. At FU visits we also observed significant improvement of MRI-derived RV ejection fraction (45.1±9.6% to 52.4±12.9%, p=0.01), and mPAP (50.5±18.3 to 42.8±18.6 mmHg, p=0.03).

Conclusions
Effective PAH therapy have an impact on both LGE mass and FDG uptake in cardiac local tissue changes. Since there was no correlation between LGE mass and FDG uptake RV insertion points, the question arises what the cause of these LGE changes is. Increased fibrosis should cause diminished local glucose metabolism. This phenomenon opens new questions concerning pathophysiology processes in RVIPs and requires confirmation on bigger PAH population.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Center for Science in Poland