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

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.