Right Atrial Function is Impaired in Pediatric Pulmonary Arterial Hypertension: A Multi-center Cardiovascular...

Impaired right atrial (RA) function is strongly predictive of adverse outcomes in adults with pulmonary arterial hypertension (PAH) but remains incompletely understood in pediatric PAH. In this pediatric multi-center retrospective cohort study using cardiovascular magnetic resonance imaging (CMR), we analyzed RA size and phasic function and its associations with PAH severity.

PAH and control pediatric patients from two centers who underwent CMR from 2010 to 2023 were identified. RA volumes were measured throughout the cardiac cycle using the single-plane, area-length method on a standard 4-chamber cine sequence. Total, conduit phase, and active phase stroke volume (SVi; indexed to BSA) and ejection fraction (EF) were calculated. A novel marker, the A/C ratio, was calculated as active/conduit SVi. RA size and phasic function measurements were correlated with clinical, hemodynamic, and non-RA CMR metrics of PAH severity and were associated with adverse events (Potts shunt, lung transplant listing/surgery, and/or death) using univariate and bivariate Cox proportional-hazards regression analyses. Intra- and inter-rater reliability was analyzed using intra-class correlation coefficients (ICC).

Compared to controls (n=36), children with PAH (n=72) had higher RA volumes, lower conduit phasic function, and higher active phasic function. In PAH patients, minimum RA volume, active SVi, and A/C ratio directly correlated with NT-proBNP and right ventricular (RV) size, filling pressures, and afterload, while they were inversely correlated with exercise capacity and RVEF. RA conduit EF (cEF) correlations were reversed. During median follow-up of 3.2 years [IQR 1.0, 5.9], RA cEF and A/C ratio remained independent predictors of adverse events after adjustment for common metrics of PAH severity on bivariate analysis, including RVEF (RA cEF aHR 0.91 [95% CI: 0.83-0.99]; A/C ratio aHR 1.58 [95% CI: 1.09-2.29]) and indexed pulmonary vascular resistance (RA cEF aHR 0.83 [95% CI: 0.74-0.93]; A/C ratio aHR 1.79 [95% CI: 1.34-2.41]). RA volume measurements had excellent reliability (ICC >0.97).

Correlating with disease severity, impaired RA physiology in pediatric PAH is characterized by RA dilation, reduced conduit phasic function, and compensatory augmentation of active phasic function. Assessment of RA size and phasic function is feasible and highly reproducible using standard CMR sequences.