Acute and Long-Term Effects of Aortic Compliance Decrease on Central Hemodynamics: A Modeling Analysis

Aortic compliance is an important determinant of cardiac afterload and a contributor to cardiovascular morbidity. In the present study, we sought to provide in silico insights into the acute as well as long-term effects of aortic compliance decrease on central hemodynamics. To that aim, we used a mathematical model of the cardiovascular system to simulate the hemodynamics (a) of a healthy young adult (baseline), (b) acutely after banding of the proximal aorta, (c) after the heart remodeled itself to match the increased afterload. The simulated pressure and flow waves were used for subsequent wave separation analysis. Aortic banding induced hypertension (SBP 106 mmHg at baseline versus 152 mmHg after banding), which was sustained after left ventricular (LV) remodeling. The main mechanism that drove hypertension was the enhancement of the forward wave, which became even more significant after LV remodeling (forward amplitude 30 mmHg at baseline versus 60 mmHg acutely after banding versus 64 mmHg after remodeling). Accordingly, the forward wave's contribution to the total pulse pressure increased throughout this process, while the reflection coefficient acutely decreased and then remained roughly constant. Finally, LV remodeling was accompanied by a decrease in augmentation index (AIx 13% acutely after banding versus -3% after remodeling) and a change of the central pressure wave phenotype from the characteristic Type A ("old") to Type C ("young") phenotype. These findings provide valuable insights into the mechanisms of hypertension and provoke us to reconsider our understanding of AIx as a solely arterial parameter.

Pressure and Flow Wave Propagation in Patient-Specific Models of the Arterial Tree

Philippe Reymond

Blood flow in the arterial circulation induces hemodynamic forces that play an important role in various forms of vascular diseases. Temporal variation of the wall shear stress seems to play a significant role in atherogenesis and plaque stability. Flow induced wall shear stress has been linked to growth and possibly rupture of the aneurysm wall. Hemodynamic forces are patient-specific and difficult to assess in the clinic. At present, there is no in vivo measurement technique that enables measurement of hemodynamic forces to the degree of precision needed. However, when imaging modalities used frequently in clinical routine re-create high-definition, patient geometric quantification of the blood vessel, they can be employed as a base for creating predictive hemodynamic models. Which in the case of understanding healthy vs. pathologic blood flow within the cerebral or systemic circulation, renders this an interesting approach. First, we developed a "generic 1D" distributed model of the human arterial tree including the primary systemic arteries and coupled this to a heart model. The fluid mechanics equations were solved numerically to obtain pressure and flow throughout the arterial tree. A nonlinear viscoelastic constitutive law for the arterial wall was considered while distal vessels were terminated with a three-element Windkessel model. The coronary arteries were modeled assuming a systolic flow impediment proportional to ventricular varying elastance. The model predictions were validated with noninvasive measurements of pressure and flow performed in young volunteers. Flow in the large arteries was visualized with magnetic resonance imaging, cerebral flow detected with ultrasound Doppler and blood pressure measured with applanation tonometry. Model predictions at different arterial locations compared well to measured flow and pressure waves at the same anatomical points. Thus, the generic 1D model reflected the flow and pressure measurements of the "average subject" of our volunteer population. Following the same approach as the generic 1D model, we built and validated a patient-specific model. In this case, geometric data, flow and pressure measurements were obtained for one person. The model predicted pressure and flow waveforms in good agreement with the in-vivo measurements with regards to wave shape and features. Comparison with a generic 1-D model has shown that the patient-specific model better predicted pressure and flow at specific arterial sites. Overall, the patient-specific 1-D model was able to predict pressure and flow waveforms in the main systemic circulation, whereas this was not always the case for a generic 1-D model. The inherent underestimation of energy losses of the 1-D wave propagation model, due to bifurcations, non-planarity and complex geometry, were examined. The 1-D model was compared to a rigid wall 3-D computational fluid dynamic model. Newtonian and non-Newtonian blood properties were studied and the longitudinal pressure distribution along the arteries was compared with the 1-D patient-specific model mean pressure prediction. The results indicated that pressure drop is significant only in small diameter vessels such as the precerebral and cerebral arteries. In these vessels the 1-D model in comparison to 3-D models consistently underestimated pressure drop. The complex flow patterns resulting from asymmetry and bifurcation yield shear stresses in the 3-D model that were greater than the 1-D model. A 3-D unsteady fluid structure interaction simulation in a patient-specific model was performed to simultaneously capture the flow details, given by the 3-D model, and wave propagation phenomena, provided by the 1-D model. The 3-D unsteady fluid structure interaction approach is the most computationally intense and cumbersome, but it allows physiological simulations with a high level of detail and accuracy. For instance, this approach could be relevant to obtain blood flow details in regions that are prone to atherosclerotic plaques or development of aneurysms. The 3-D fluid structure interaction simulation was performed for a patient-specific aorta. Important clinical parameters such as wall shear stress were quantified and significant differences were found in comparison to the rigid wall 3-D simulation indicating the relevance of a fluid structure interaction approach. A comparison of the fluid structure interaction to an equivalent 1-D model resulted in good reproduction of the pressure and flow waveforms. The effect of a decreased compliance of the arterial tree on hemodynamical parameters has been assessed with the use of a 1-D model. Local, proximal aorta and global stiffening of the arterial tree were modeled and led to two different mechanisms that contribute to the increase in central pulse pressure. They probably both contribute to systolic hypertension and their relative contribution depends on the topology of arterial stiffening and geometrical alterations taking place in aging or in disease. All these patient-specific models are about to being in use in a clinical environment and will be useful for providing better diagnostics and treatment planning in a near future.

EPFL2011

Hemodynamics of ageing, ventricular-arterial coupling and noninvasive assessment of key hemodynamical and cardiac quantities

Stamatia Zoi Pagoulatou

Ageing is a natural process that affects both the anatomical and functional properties of the cardiovascular system and alters the coupling characteristics between the heart and the aorta. These alterations may predispose the cardiovascular system in the development and progression of cardiovascular diseases (CVD), such as hypertension and left ventricular (LV) hypertrophy. CVDs are currently the leading cause of morbidity and mortality globally, and with the population of elderly steadily increasing, they are expected to become socio-economic burden in the near future. Accordingly, the presented body of research aimed at providing novel insights into the evolution of hemodynamics with ageing (Part I) and the physiology of the ventricular-arterial interaction (Part II) by leveraging the potential of a state-of-the-art one-dimensional (1D) model of the systemic circulation. A major goal of this dissertation was also the development, implementation and validation of novel noninvasive tools for monitoring biomarkers of importance (Part III), as well as the evaluation of existing or novel techniques to derive aortic biomechanical properties (Part IV). In Part I, we presented a validated 1D model of the systemic circulation that was adjusted to account for the effects of ageing, as reported by previous literature. The ageing model was found highly consistent with published data from large-scale studies. Examination of the wave reflection profile revealed an increase in the forward wave amplitude over time, which constitutes the principal determinant of the age-induced increase in systolic pressure. Additionally, we highlighted the importance of considering the heterogeneous effects of ageing on the arterial distensibility when adapting the properties of the arterial tree model, in order to predict correctly central hemodynamics. In Part II, we focused on the effect of cardiac systolic function on central and peripheral hemodynamics under physiological and pathological conditions. By means of our computational 1D model, we showed that a physiological increase in cardiac contractility leads to a steeper forward pressure wave pumped by the heart, which, subsequently, drastically alters central and peripheral hemodynamics. These computational results were in good agreement with our subsequent in vivo study, conducted in a group of aortic valve stenosis patients subjected to Transcatheter Aortic Valve Replacement. Part III of this thesis was devoted to the design, development, testing and validation of a method to achieve cardiac and hemodynamic monitoring based on simple, readily available, noninvasive measurements. The concept is based on the personalization of the parameters of the mathematical model of the cardiovascular system according to patient data, and the subsequent derivation of cardiovascular properties in a reverse-engineering approach. Finally, in Part IV, we evaluated existing and novel methods for the assessment of the biomechanical properties of the aorta. We first investigated whether local aortic area compliance, measured as lumen area changes over pulse pressure, is an appropriate index of volume compliance or distensibility when applied to the proximal aorta. In a second analysis, we focused our attention on measures of regional aortic compliance. More specifically, we examined the potential of using compressed-sensing 4D Flow MRI to reliably estimate aortic pulse wave velocity.

EPFL2020

Acute effects of transcatheter aortic valve replacement on the ventricular-aortic interaction

Vasiliki Bikia, Stamatia Zoi Pagoulatou, Georgios Rovas, Nikolaos Stergiopulos

Transcatheter aortic valve replacement (TAVR) is increasingly used to treat severe aortic stenosis (AS) patients. However, little is known regarding the direct effect of TAVR on the ventricular-aortic interaction. In the present study, we aimed to investigate changes in central hemodynamics after successful TAVR. We retrospectively examined 33 cases of severe AS patients (84 +/- 6 yr) who underwent TAVR. Invasive measurements of left ventricular and aortic pressures as well as echocardiographic aortic flow were acquired before and after TAVR (maximum within 5 days). We examined alterations in key features of central pressure and flow waveforms, including the aortic augmentation index (AIx), and performed wave separation analysis. Arterial parameters were determined via parameter-fitting on a two-element Windkessel model. Resolution of AS resulted in direct increase in the aortic systolic pressure and maximal aortic flow (131 +/- 22 vs. 157 +/- 25 mmHg and 237 +/- 49 vs. 302 +/- 69 mL/s, P < 0.001 for all), whereas the ejection duration decreased (P < 0.001). We noted a significant decrease in the AIx (from 42 +/- 12 to 19 +/- 11%, P < 0.001). Of note, the arterial properties remained unchanged. There was a comparable increase in both forward (61 +/- 20 vs. 77 +/- 20 mmHg, P < 0.001) and backward ( 35 +/- 14 vs. 42 +/- 10 mmHg, P = 0.013) pressure wave amplitudes, while their ratio, i.e., the reflection coefficient, was preserved. Our results highlight the impact of TAVR on the ventricular-aortic interaction by affecting the amplitude, shape, and related attributes of the aortic pressure and flow pulse and challenge the interpretation of AIx as a solely vascular measure in AS patients. NEW & NOTEWORTHY Transcatheter aortic valve replacement (TAVR) is linked with an immediate increase in aortic systolic blood pressure and maximal flow, as well as steeper aortic pressure and flow wave upstrokes. After TAVR, the forward wave pumped by the heart is enhanced. Although the arterial properties remain unchanged, the central augmentation index (AIx) is markedly decreased after TAVR. This challenges the interpretation of AIx as a solely vascular measure in patients with aortic valve stenosis.

AMER PHYSIOLOGICAL SOC2020