Initial clinical validation of a hybrid in silico—in vitro cardiorespiratory simulator for comprehensive testing of mechanical circulatory support systems

Libera Fresiello*, Kavitha Muthiah, Kaatje Goetschalckx, Christopher Hayward, Maria Rocchi, Maxime Bezy, Jo P. Pauls, Bart Meyns, Dirk W. Donker, Krzysztof Zieliński

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Simulators are expected to assume a prominent role in the process of design—development and testing of cardiovascular medical devices. For this purpose, simulators should capture the complexity of human cardiorespiratory physiology in a realistic way. High fidelity simulations of pathophysiology do not only allow to test the medical device itself, but also to advance practically relevant monitoring and control features while the device acts under realistic conditions. We propose a physiologically controlled cardiorespiratory simulator developed in a mixed in silico-in vitro simulation environment. As inherent to this approach, most of the physiological model complexity is implemented in silico while the in vitro system acts as an interface to connect a medical device. As case scenarios, severe heart failure was modeled, at rest and at exercise and as medical device a left ventricular assist device (LVAD) was connected to the simulator. As initial validation, the simulator output was compared against clinical data from chronic heart failure patients supported by an LVAD, that underwent different levels of exercise tests with concomitant increase in LVAD speed. Simulations were conducted reproducing the same protocol as applied in patients, in terms of exercise intensity and related LVAD speed titration. Results show that the simulator allows to capture the principal parameters of the main adaptative cardiovascular and respiratory processes within the human body occurring from rest to exercise. The simulated functional interaction with the LVAD is comparable to the one clinically observed concerning ventricular unloading, cardiac output, and pump flow. Overall, the proposed simulation system offers a high fidelity in silico-in vitro representation of the human cardiorespiratory pathophysiology. It can be used as a test bench to comprehensively analyze the performance of physically connected medical devices simulating clinically realistic, critical scenarios, thus aiding in the future the development of physiologically responding, patient-adjustable medical devices. Further validation studies will be conducted to assess the performance of the simulator in other pathophysiological conditions.

Original languageEnglish
Article number967449
JournalFrontiers in Physiology
Publication statusPublished - 13 Oct 2022


  • 0D models
  • artificial organs
  • cardiorespiratory simulator
  • exercise physiology
  • in vitro simulator
  • lumped parameter model
  • mechanical circulatory support
  • ventricular assist device


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