Integrating Computational and Biological Hemodynamic Approaches to Improve Modeling of Atherosclerotic Arteries.

Atherosclerosis is the primary cause of cardiovascular disease, resulting in mortality, elevated healthcare costs, diminished productivity, and reduced quality of life for individuals and their communities. This is exacerbated by the limited understanding of its underlying causes and limitations in current therapeutic interventions, highlighting the need for sophisticated models of atherosclerosis. This review critically evaluates the computational and biological models of atherosclerosis, focusing on the study of hemodynamics in atherosclerotic coronary arteries. Computational models account for the geometrical complexities and hemodynamics of the blood vessels and stenoses, but they fail to capture the complex biological processes involved in atherosclerosis. Different in vitro and in vivo biological models can capture aspects of the biological complexity of healthy and stenosed vessels, but rarely mimic the human anatomy and physiological hemodynamics, and require significantly more time, cost, and resources. Therefore, emerging strategies are examined that integrate computational and biological models, and the potential of advances in imaging, biofabrication, and machine learning is explored in developing more effective models of atherosclerosis.

Be still, my beating heart: reading pulselessness from Shakespeare to the artificial heart.

Today, patients with heart failure can be kept alive by an artificial heart while they await a heart transplant. These modern artificial hearts, or left ventricular assist devices (LVADs), remove the patient's discernible pulse while still maintaining life. This technology contradicts physiological, historical and sociocultural understandings of the pulse as central to human life. In this essay, we consider the ramifications of this contrast between the historical and cultural importance placed on the pulse (especially in relation to our sense of self) and living with a pulseless LVAD. We argue that the pulse's relationship to individual identity can be rescripted by examining its representation in formative cultural texts like the works of William Shakespeare. Through an integration of historical, literary and biomedical engineering perspectives on the pulse, this paper expands interpretations of pulselessness and advocates for the importance of cultural-as well as biomedical-knowledge to support patients with LVADs and those around them. In reconsidering figurative and literal representations of the heartbeat in the context of technology which removes the need for a pulse, this essay argues that narrative and metaphor can be used to reconceptualise the relationship between the heartbeat and identity.

A computational framework for adjusting flow during peripheral extracorporeal membrane oxygenation to reduce differential hypoxia.

Peripheral veno-arterial extra corporeal membrane oxygenation (VA-ECMO) is an established technique for short-to-medium support of patients with severe cardiac failure. However, in patients with concomitant respiratory failure, the residual native circulation will provide deoxygenated blood to the upper body, and may cause differential hypoxemia of the heart and brain. In this paper, we present a general computational framework for the identification of differential hypoxemia risk in VA-ECMO patients. A range of different VA-ECMO patient scenarios for a patient-specific geometry and vascular resistance were simulated using transient computational fluid dynamics simulations, representing a clinically relevant range of values of stroke volume and ECMO flow. For this patient, regardless of ECMO flow rate, left ventricular stroke volumes greater than 28 mL resulted in all aortic arch branch vessels being perfused by poorly-oxygenated systemic blood sourced from the lungs. The brachiocephalic artery perfusion was almost entirely derived from blood from the left ventricle in all scenarios except for those with stroke volumes less than 5 mL. Our model therefore predicted a strong risk of differential hypoxemia in nearly all situations with some residual cardiac function for this combination of patient geometry and vascular resistance. This simulation highlights the potential value of modelling for optimising ECMO design and procedures, and for the practical utility for personalised approaches in the clinical use of ECMO.

Hemodynamic response to exercise and head-up tilt of patients implanted with a rotary blood pump: a computational modeling study.

The present study investigates the response of implantable rotary blood pump (IRBP)-assisted patients to exercise and head-up tilt (HUT), as well as the effect of alterations in the model parameter values on this response, using validated numerical models. Furthermore, we comparatively evaluate the performance of a number of previously proposed physiologically responsive controllers, including constant speed, constant flow pulsatility index (PI), constant average pressure difference between the aorta and the left atrium, constant average differential pump pressure, constant ratio between mean pump flow and pump flow pulsatility (ratioP I or linear Starling-like control), as well as constant left atrial pressure ( P l a ¯ ) control, with regard to their ability to increase cardiac output during exercise while maintaining circulatory stability upon HUT. Although native cardiac output increases automatically during exercise, increasing pump speed was able to further improve total cardiac output and reduce elevated filling pressures. At the same time, reduced venous return associated with upright posture was not shown to induce left ventricular (LV) suction. Although P l a ¯ control outperformed other control modes in its ability to increase cardiac output during exercise, it caused a fall in the mean arterial pressure upon HUT, which may cause postural hypotension or patient discomfort. To the contrary, maintaining constant average pressure difference between the aorta and the left atrium demonstrated superior performance in both exercise and HUT scenarios. Due to their strong dependence on the pump operating point, PI and ratioPI control performed poorly during exercise and HUT. Our simulation results also highlighted the importance of the baroreflex mechanism in determining the response of the IRBP-assisted patients to exercise and postural changes, where desensitized reflex response attenuated the percentage increase in cardiac output during exercise and substantially reduced the arterial pressure upon HUT.

Evaluation of a morphological filter in mean cardiac output determination: application to left ventricular assist devices.

A morphological filter (MF) is presented for the determination of beat-to-beat mean rotary left ventricular assist device (LVAD) flow rate, measured using an implanted flow probe. The performance of this non-linear filter was assessed using LVAD flow rate (QLVAD) data sets obtained from in silico and in vivo sources. The MF was compared with a third-order Butterworth filter (BWF) and a 10-s moving average filter (MAF). Performance was assessed by calculating the response time and steady state error across a range of heart rates and levels of noise. The response time of the MF was 3.5 times faster than the MAF, 0.5 s slower than the BWF, and had a steady state error of 2.61 %. It completely removed pulsatile signal components caused by residual ventricular function, and tracked sharp transient changes in QLVAD better than the BWF. The use of a two-stage MF improved the noise immunity compared to the single-stage MF. This study showed that the good performance characteristics of the non-linear MF make it a more suitable candidate for embedded real-time processing of QLVAD than linear filters.

Frank-starling control of a left ventricular assist device.

A physiological control system was developed for a rotary left ventricular assist device (LVAD) in which the target pump flow rate (LVADQ) was set as a function of left atrial pressure (LAP), mimicking the Frank-Starling mechanism. The control strategy was implemented using linear PID control and was evaluated in a pulsatile mock circulation loop using a prototyped centrifugal pump by varying pulmonary vascular resistance to alter venous return. The control strategy automatically varied pump speed (2460 to 1740 to 2700 RPM) in response to a decrease and subsequent increase in venous return. In contrast, a fixed-speed pump caused a simulated ventricular suction event during low venous return and higher ventricular volumes during high venous return. The preload sensitivity was increased from 0.011 L/min/mmHg in fixed speed mode to 0.47L/min/mmHg, a value similar to that of the native healthy heart. The sensitivity varied automatically to maintain the LAP and LVADQ within a predefined zone. This control strategy requires the implantation of a pressure sensor in the left atrium and a flow sensor around the outflow cannula of the LVAD. However, appropriate pressure sensor technology is not yet commercially available and so an alternative measure of preload such as pulsatility of pump signals should be investigated.