Richard M Friesen1,2, Michal Schäfer1,3, D Dunbar Ivy1, Steven H Abman4, Kurt Stenmark5, Lorna P Browne6, Alex J Barker7, Kendall S Hunter1,3, Uyen Truong1. 1. Division of Cardiology, Heart Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, 13123 E 16th Avenue, Aurora, CO, USA. 2. Department of Critical Care, Seattle Children's Hospital, University of Washington, 4800 Sand Point Way NE, Seattle, WA, USA. 3. Department of Bioengineering, College of Engineering and Applied Sciences, University of Colorado Denver, Anschutz Medical Campus, 12705 E. Montview Ave, Aurora, CO, USA. 4. Division of Pulmonology, Breathing Institute, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, 13123 E 16th Avenue, Aurora, CO, USA. 5. Developmental Lung Biology and Cardiovascular Pulmonary Research Laboratories, University of Colorado Denver, Anschutz Medical Campus, 12700 E 19th Ave, Box B131. Aurora, CO, USA. 6. Department of Radiology, Children's Hospital Colorado, University of Colorado Denver, Anschutz Medical Campus, 13123 E 16th Avenue, Aurora, CO, USA. 7. Department of Radiology, Feinberg School of Medicine, Northwestern University, 737 N Michigan Ave, Suite 1600, Chicago, IL, USA.
Abstract
Aims: Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Methods and results: Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2-fold increase in having a moderate clinical event. Conclusion: MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH.
Aims: Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Methods and results: Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2-fold increase in having a moderate clinical event. Conclusion: MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH.
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