Parameter inference in a computational model of haemodynamics in pulmonary hypertension. Issue 200 (1st March 2023)

• Record Type: Journal Article
• Authors: Colunga, Amanda L.; Colebank, Mitchel J.; Olufsen, Mette S.
• Is Part Of: Journal of the Royal Society interface. Volume 20:Issue 200(2023)
• Publication Date: 2023-03-01
• Subjects: pulmonary hypertension -- computational model -- parameter inference -- cardiovascular modelling; Physical sciences -- Research -- Periodicals; Life sciences -- Research -- Periodicals; Interdisciplinary research -- Periodicals; 570.5
• DOI: 10.1098/rsif.2022.0735
• Languages: English
• ISSNs: 1742-5689

Abstract

Abstract : Pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg, is characterized by increased pulmonary vascular resistance and decreased pulmonary arterial compliance. There are few measurable biomarkers of PH progression, but a conclusive diagnosis of the disease requires invasive right heart catheterization (RHC). Patient-specific cardiovascular systems-level computational models provide a potential non-invasive tool for determining additional indicators of disease severity. Using computational modelling, this study quantifies physiological parameters indicative of disease severity in nine PH patients. The model includes all four heart chambers, the pulmonary and systemic circulations. We consider two sets of calibration data: static (systolic and diastolic values) RHC data and a combination of static and continuous, time-series waveform data. We determine a subset of identifiable parameters for model calibration using sensitivity analyses and multi-start inference and perform posterior uncertainty quantification. Results show that additional waveform data enables accurate calibration of the right atrial reservoir and pump function across the PH cohort. Model outcomes, including stroke work and pulmonary resistance-compliance relations, reflect typical right heart dynamics in PH phenotypes. Lastly, we show that estimated parameters agree with previous, non-modelling studies, supporting this type of analysis in translational PH research.