4-D flow magnetic-resonance-imaging-derived energetic biomarkers are abnormal in children with repaired tetralogy of Fallot and associated with disease severity

Background: Cardiac MRI plays a central role in monitoring children with repaired tetralogy of Fallot (TOF) for long-term complications. Current risk assessment is based on volumetric and functional parameters that measure late expression of underlying physiological changes. Emerging 4-D flow MRI techniques promise new insights. Objective: To assess whether 4-D flow MRI-derived measures of blood kinetic energy (1) differentiate children and young adults with TOF from controls and (2) are associated with disease severity. Materials and methods: Pediatric patients post TOF repair (n=21) and controls (n=24) underwent 4-D flow MRI for assessment of time-resolved 3-D blood flow. Data analysis included 3-D segmentation of the right ventricle (RV) and pulmonary artery (PA), with calculation of peak systolic and diastolic kinetic energy (KE) maps. Total KE _RV and KE _PA were determined from the sum of the KE of all voxels within the respective time-resolved segmentations. Results: KE _PA was increased in children post TOF vs. controls across the cardiac cycle, with median 12.5 (interquartile range [IQR] 10.3) mJ/m ² vs. 8.2 (4.3) mJ/m ² , P<0.01 in systole; and 2.3 (2.7) mJ/m ² vs. 1.4 (0.9) mJ/m ² , P<0.01 in diastole. Diastolic KE _PA correlated with systolic KE _PA (R ² 0.41, P<0.01) and with pulmonary regurgitation fraction (R ² 0.65, P<0.01). Diastolic KE _RV showed similar relationships, denoting increasing KE with higher cardiac outputs and increased right heart volume loading. Diastolic KE _RV and KE _PA increased with RV end-diastolic volume in a non-linear relationship (R ² 0.33, P<0.01 and R ² 0.50, P<0.01 respectively), with an inflection point near 120 mL/m ² . Conclusion: Four-dimensional flow-derived KE is abnormal in pediatric patients post TOF repair compared to controls and has a direct, non-linear relationship with traditional measures of disease progression. Future longitudinal studies are needed to evaluate utility for early outcome prediction in TOF.