A Closed-Loop Lumped-Parameter Cardiovascular Model of the Supine-to-Stand Manoeuvre and Its Association with Falls
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The risk of falling increases significantly with age, and orthostatic hypotension (OH) is a common cardiovascular contributor to falls [1]. Unfortunately, OH is often diagnosed only after a fall. Current diagnostic criteria for OH rely on momentary blood pressure measurements, which may not fully capture the underlying causes of the condition. To address this, we are developing a computational model of the cardiovascular system to better understand the underlying causes of OH, which could in turn lead to more informed diagnostics. Our 23-compartment lumped cardiovascular model [2] includes baroreflex regulation, venous pooling, and a time-varying elastance heart model. It was calibrated using Finapres data from older adults (Nijmegen Radboud University PROHEALTH study) performing supine-to-stand manoeuvres. We optimized 31 model parameters using the Stochastic Ranking Evolutionary Strategy. At the population level, the model reproduced systolic and diastolic blood pressure and heart rate responses with normalized root mean squared errors of 12.7%, 6.8%, and 9.0% for fallers, and 8.4%, 9.5%, and 9.9% for non-fallers, respectively. Four of the 31 parameters showed significant differences between fallers and non-fallers: baroreflex reference heart rate, stand-up muscle pressure, total blood volume, and the baroreflex shape parameter. Future work includes performing global sensitivity analysis, and applying parameter clustering and reduction techniques to improve parameter identifiability. Ultimately, the goal is to develop individualized digital twins of OH patients, including cerebral circulation, validated against a larger, independent dataset, including NIRS measurements. REFERENCES [1] Soysal P, et al. Orthostatic hypotension and health outcomes: an umbrella review of observational studies. Eur Geriatr Med. 2019;10(6):863-870. doi:10.1007/s41999-019-00239-4 [2] van Loon LM, et al. Computational modeling of orthostatic intolerance for travel to Mars. NPJ Microgravity. 2022;8(1):34. doi:10.1038/s41526-022-00219-2
