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 and KE were determined from the sum of the KE of all voxels within the respective time-resolved segmentations.

Results: KE was increased in children post TOF vs. controls across the cardiac cycle, with median 12.5 (interquartile range [IQR] 10.3) mJ/m vs. 8.2 (4.3) mJ/m, P<0.01 in systole; and 2.3 (2.7) mJ/m vs. 1.4 (0.9) mJ/m, P<0.01 in diastole. Diastolic KE correlated with systolic KE (R 0.41, P<0.01) and with pulmonary regurgitation fraction (R 0.65, P<0.01). Diastolic KE showed similar relationships, denoting increasing KE with higher cardiac outputs and increased right heart volume loading. Diastolic KE and KE increased with RV end-diastolic volume in a non-linear relationship (R 0.33, P<0.01 and R 0.50, P<0.01 respectively), with an inflection point near 120 mL/m.

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.