During the cardiac cycle, the apex of the heart remains stationary since the heart cannot move out of the fluid-tight pericardial sac, which is tethered to the diaphragm. Additionally, the apex of the pericardium is connected to the caudal sternum via the sterno-pericardial ligament, interlinking the caudal sternum with the LV-apex. This creates a relatively straight line of force between the stationary LV-apex[6] at the caudal end, and the aortic arch[4] at the cranial end with the aortic root in between that propels up and down by (16.4 ± 0.5mm) during the cardiac cycle, when the LV-shortens and the AA get stretched.[3] [6]
The present computational simulation demonstrates that stiffening of the AA increases myocardial stress which affects LV strain patterns. Myofiber stress increased overall in the LV with high-stress areas noted at the septum, the papillary muscles, the mitral annulus, the fibrous trigones, and the aorto-mitral junction. The most pronounced reduction in strain was noted along the septal longitudinal region, the direct connection between the LV-apex and the aortic root. This is of particular relevance since LV longitudinal shortening is a major contributor to heart contraction, accounting for 60% of the LV stroke volume and 80% of the right ventricular (RV) stroke volume.[6] The pressure-volume loops revealed that aortic root stiffening caused a deterioration in LV function with increased end systolic volume, reduced systolic LV pressure, decreased stroke volume, and effective stoke work with elevated end-diastolic pressure.
Increased myofiber contractility pressure-volume loops indicated that stroke volume and effective stroke work could theoretically be recovered, end-systolic LV pressure could be increased, end-diastolic pressure reduced. Longitudinal and radial strains remained reduced, but the circumferential strains increased over baseline, compensating for lost longitudinal LV function. But myofibers demonstrated, at the same time, increased overall stress. The most dramatic increase in myofiber stress was found at the septal region, the apex of the LV, and at the papillary muscles. When the papillary muscle contracts the mitral valve tertiary, stay chordae pull the center of the atrioventricular plane, including aortic root at the aorto-mitral curtain towards the LV apex, supporting in this way, the aorto-mitral angle and the displacement of the aortic root in systole[23] what explains the increased stress observed at the fibrose trigones and the papillary muscles.
It is well-recognized that arterial stiffening increases with age.[5] [24] [25] [26] [24] [27] [28] Aortic stiffening is known to cause: reduced arterial compliance (elasticity), impaired aorto-ventricular interaction, pronounced reduction of longitudinal left ventricular function, reduced long axis strain, impaired early diastolic filling of the ventricle, higher left ventricular afterload and higher end diastolic left atrial pressure.[5, 7] [29] [30]
In animals, a stiff aorta significant increases myocardial oxygen consumption by 30% and increase of energetic costs for the heart for delivering a given stroke volume by 20–40% [31]. As a stiff ascending aorta would be displaced and stretched less than a compliant aorta would, the heart would have to contract with greater long-axis force to produce the same amount of aortic displacement and stroke volume [32].
It was demonstrated in humans that increased aortic stiffness is associated with reduced global longitudinal strain. [5] [24] [33] [34] [35] and authors concluded that LV long-axis shortening, and global longitudinal strain may be reduced when pulling against a stiffer aorta because of a potential mechanical ventricular–vascular interaction. Consequently, when the aorta stiffens, the heart must contract with greater long-axis force in order to produce the same amount of aortic displacement.[5] This is consistent with our results showing that aortic stiffening imposes a direct mechanical load on the long-axis LV function.
This in silico study provides valuable insights into the influence of ascending aorta stiffness on the function of the left ventricle, with a focus on conditions such as heart failure with reduced ejection fraction (HFpEF). The simulation results underscore the intimate mechanical coupling between the ascending aorta and the left ventricle and highlight a new potential pathophysiological mechanism underpinning HFpEF. The simulations suggest that a stiffened ascending aorta may significantly affect key markers of cardiac function such as increase in end-diastolic pressure and a decrease in end-systolic pressure, stroke volume, and effective stroke work. Furthermore, the geometric impact of aortic stiffness on the left ventricle manifested as a tendency for ovalization at end-systole, pointing to a reconfiguration of the cardiac architecture due to increased aortic stiffness. Strikingly, these alterations in LV function were also accompanied by distinct changes in myocardial strain and stress parameters. This was evidenced by reduced tensile radial strain, compressive circumferential strain and longitudinal strain, as well as an increase in myofiber stress, particularly along the septum of the left ventricle. These results underscore the hypothesis of a mechanical coupling between the ascending aorta and the left ventricle, where aortic stiffness may directly contribute to altered LV function.
Elevated mechanical stress leads to alterations in biochemical signaling pathways that can activate maladaptive hypertrophic responses. While short-term hypertrophy may be a compensatory mechanism, chronic hypertrophy can lead to systolic heart failure. [36] Under chronic stress activated fibroblasts and myofiboblasts are the central effectors in cardiac fibrosis [37] [38] eventually leading to impaired relaxation and filling of the left ventricle, and diastolic left ventricular failure. The increased end-diastolic pressure observed in our model aligns with this pathological state, indicating the potential of progression towards HFpEF.
This simulation study, although exploratory and hypothesis-generating in nature, provides a compelling argument for further investigations into the mechanical interplay between the ascending aorta elasticity and left ventricle function. Understanding the extent to which stiffness of the ascending aorta can influence ventricular function may lead to novel diagnostic and therapeutic strategies in managing heart failure. Given the high prevalence of aortic stiffness and impaired left ventricular longitudinal strain in patients with HFpEF, these findings provide a rationale for further research into therapies targeting ascending aorta stiffness and its downstream effects on ventricular function.