Modelling and simulation of the cardiovascular system and the Istanbul heart ventricular assist device

Heart transplantation rates are limited due to high donor heart rejection rates and the rising number of heart failure (HF) patients due to a growing and ageing population. Left Ventricular assist Devices (LVADs) are increasingly being implanted as a buttress against advanced-stage heart failure. However, they are associated with a multitude of complications. LVAD design and development is a thorough pro cess involving many steps before they can acquire approval from regulatory bodies, involving virtual testing in-silico, verification of the results in-vitro, validation of performance in animals, i.e., in-vivo, and ultimately clinical trials. As we progress along its different phases, the development process becomes more complex, less controllable, and more costly. Under such circumstances, reliable pre-clinical evaluation becomes imperative. The current work makes use of two pre-clinical models namely numerical modelling and mock circulatory loops. An intuitive and knowledge-based approach to numerical modelling is adopted whereby model components are con nected in a topological manner without explicitly coding model equations. Mathworks' Simscape (TM) modelling environment is used to develop a comprehensive and real-time executable model of the cardiovascular system (CVS) and the Istanbul Heart (iHeart) VAD. The CVS model is developed by combining existing models and the VAD model is an analytically-derived model calibrated using iHeart VAD's characteristic data. A baseline is established by calibrating the CVS model with healthy heart parameters. Parameters for Dilated Cardiomyopathy (DCM), a sub set of Heart Failure with Reduced Ejection Fraction (HFrEF), are collected from published patient data and disease modelling is conducted using statistically pooled values. To simulate iHeart VAD support, it is anatomized to the left ventricle apex and the ascending aorta in Simscape (TM). CVS-VAD modelling is applied for in-silico adaptation of hemodynamic ramp testing, an invasive clinical procedure which can potentially support clinical decision-making before conducting such an invasive procedure by exploring the possibility of improvements preemptively. It is also used to conduct a full factorial design of experiments to study the functional relationships between CVS parameters and LVAD suction speed which can be used to guide the development of suction detection and avoidance control algorithms. CVS-VAD model is also used to develop a numerical-hydraulic hybrid mock circulatory loop to study the behaviour of the iHeart VAD in-vitro. The adopted modelling approach results in a more realistic replication of the physiological environment an LVAD is exposed to. A comprehensive framework for the pre-clinical evaluation of mechani cal circulatory support devices is provided. Due to its object-oriented and modular nature, the featured model can be readily modified for other cardiovascular diseases. In addition to facilitating LVAD research, the presented work provides a teaching tool for understanding the pathophysiology of heart failure, diagnosis rationale, and degree of assist requirements. Utilization of in-silico and in-vitro approaches provide complementary information, allowing device behaviour and performance prediction and enhancing model accuracy.