Role of baroreflex feedback loop in predictions of left ventricular growth: A multiscale finite element modelling study

The heart functions within a complex system that adapts its function to alterations in loading via several mechanisms. For example, the baroreflex is a feedback loop that modulates the heart's function on a beat-to-beat basis to control arterial pressure. On the other hand, cardiac growth is an adaptive process that occurs over weeks or months in response to changes in left ventricular loading. In this study, we investigate the impact of a baroreflex feedback loop on left ventricular growth in simulations of valve disease. To achieve this, we integrated the effects of a baroreflex feedback loop and a growth algorithm into a beating multiscale finite element model of the left ventricle. Our integrated model replicated clinical measures of left ventricular growth in two types of valvular diseases - aortic stenosis and mitral regurgitation - at two different levels of severity for each case. Furthermore, our results showed that incorporating the effects of baroreflex control in simulations of left ventricular growth not only led to more realistic haemodynamics, but also impacted the magnitude of growth. Finally, our results suggest that the regulation of Ca 2+ dynamics by the baroreflex is a crucial mechanism in adapting the myocardial cell in response to altered loading due to aortic stenosis and mitral regurgitation. KEY POINTS: The heart adapts its function in response to alterations in loading via short-term and long-term mechanisms. These mechanisms are essential for maintaining proper blood pressure in the vasculature (baroreflex) and homeostasis in the heart (ventricular growth). In this study, we investigate the impact of a baroreflex feedback loop on left ventricular growth in finite element simulations of valve disease. We showed that incorporating the effects of baroreflex control and ventricular growth not only led to more realistic haemodynamics, but also impacted the magnitude of growth. Our results suggest that the regulation of Ca 2⁺ dynamics by the baroreflex is a crucial mechanism in adapting the myocardial cell in response to altered ventricular loading.