Mechanistic haemodynamic evaluation of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension using digital twin–derived right ventricular–pulmonary arterial coupling
L Mizuhara, M Fukumitsu, T Nishikawa, R Takano, N Hiraki, S Fujisaki, H Hayashi, R Asano, T Ogo, K SakuAbstract
Background/Introduction
Balloon pulmonary angioplasty (BPA) is an established treatment for chronic thromboembolic pulmonary hypertension (CTEPH) that reduces pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (mPAP), thereby decreasing right ventricular (RV) afterload. However, cardiac output (CO) improvement after BPA is variable and often modest, and its mechanism remains unclear. We hypothesised that this heterogeneity reflects right ventricular-pulmonary arterial coupling. The gold-standard coupling metric is the end-systolic elastance-to-arterial elastance ratio (Ees/Ea), but assessment requires invasive pressure-volume measurements and expertise. We therefore used Bayesian optimisation to construct haemodynamic digital twins, estimate Ees/Ea from routine data, and test whether baseline Ees/Ea explains heterogeneity in CO response after BPA.
Purpose
To test whether baseline model-derived Ees/Ea stratifies the CO response at 3 months after BPA in CTEPH.
Methods
We studied 45 CTEPH patients treated with BPA. Patient-specific digital twins were created by tuning 13 cardiovascular parameters, including end-systolic elastance (Ees) and arterial elastance (Ea), through Bayesian optimisation using echocardiography, right heart catheterisation and cardiac magnetic resonance imaging at baseline and 3 months post-BPA. Receiver operating characteristic (ROC) analysis determined a baseline Ees/Ea cutoff for RV dysfunction, and patients were categorised as Coupled or Uncoupled. Outcomes were analysed using linear mixed models with fixed effects for time, group, and the time-by-group interaction, and a random intercept for each subject. When the interaction was significant, model-based simple-effects comparisons were performed with Holm's method for multiple testing.
Results
ROC analysis yielded an Ees/Ea cutoff of 0.76, classifying 27 patients as Coupled (Ees/Ea >= 0.76) and 18 as Uncoupled (Ees/Ea < 0.76). At baseline, the Uncoupled group showed a more severe clinical profile (Coupled vs Uncoupled: B-type natriuretic peptide (BNP) 33.8 vs 163.9 pg/mL; RV end-diastolic volume (RVEDV) 117 vs 158 mL; CO 4.0 vs 3.0 L/min; mPAP 33 vs 43 mmHg; PVR 7.1 vs 12.8 Wood units). Ees was similar between groups, whereas Ea was higher in Uncoupled patients (1.31 vs 2.36 mmHg/mL), resulting in lower Ees/Ea (1.09 vs 0.58). Linear mixed models showed significant time-by-group interactions across prespecified outcomes (all p<0.001). Model-based simple effects showed that CO increased after BPA in the Uncoupled group (3.0 to 4.0 L/min, p<0.001) but not in the Coupled group (4.0 to 3.5 L/min, p>0.99). Ees/Ea increased in the Uncoupled group (0.56 to 1.09) but remained unchanged in the Coupled group; mPAP and PVR decreased in both groups.
Conclusion
Haemodynamic digital twin-derived Ees/Ea identified baseline right ventricular-pulmonary arterial uncoupling and stratified CO improvement after BPA in CTEPH.Figure1For image description, please refer to the figure legend and surrounding text.Figure2For image description, please refer to the figure legend and surrounding text.