Abstract:
Heart Failure with preserved ejection fraction (HFpEF) has emerged as a prevalent heart disease which has high risk of short-term and long-term mortality rate. HFpEF has been associated with a progressively impaired interaction between the left ventricle (LV) and the systemic arteries. The progression of HFpEF along with the key factors which contributes to this process, is an area of active research. Since the structural and functional changes of Left Ventricle (LV) governs the progression of HFpEF, computational models have emerged as a robust tool to study the features of HFpEF as well as to develop effective treatment plan in recent years. FE model of LV would help to assess the contributions of the key factors to the progression of HFpEF. In the present study a coupled LV FE-lumped parameter circulatory modeling framework has been developed and calibrated with the measurements acquired from a normal subject and a HFpEF patient. The models for normal and HFpEF cases reproduced the clinical datasets within acceptable limits though the longitudinal strain was found nearly equal for both the cases, which can be a consequence of higher ejection fraction found in the HFpEF case. After that, the HFpEF model parameters such as, geometry (thickness 1 – 1.9 cm), preload (LV end diastolic volume 144.6 – 194.9 ml), afterload (110000 - 192500 Pa ms ml−1), and transmural myofiber orientation (fiber angle -50o/50o to -70o/70o), were varied to physiologically reproduce the effects of these parameters on progression of HFpEF due to remodeling, diastolic dysfunction, hypertension, hypertrophy etc. which are the causes and effects of HFpEF progression. The model predicts features of HFpEF progression except increased circumferential strain as LV wall thickness is increased, which is found in HFpEF patient. Reduced preload replicated the prominent feature of HFpEF progression that is, decrease in longitudinal strain. So increased LV wall thickness with reduced preload can be a possible path of HFpEF progression. Increasing afterload predicts decrease in both circumferential and longitudinal strains, but the associated systolic pressure shows unphysiological increment. Change in fiber angle has negligible effect on LV functioning, but has a considerable effect on strains. It has been found that, though isolated variation of these parameters shows contribution towards progression of HFpEF, but it is likely that more than one mechanism has to be combined to reproduce all the pathophysiological features found during the progression of HFpEF.
