32460 Sex and heart failure: different pathophysiology or inadequate diagnostic criteria? A biomechanical modelling study.
Richtingen: Master of Science in Biomedical Engineering

Probleemstelling:

There is an increasing awareness that there is sex-bias in cardiovascular medicine, and that the (average) female heart is not simply a scaled down version of the (average) male heart. In addition to potential differences in the pathophysiology of the disease, there is a growing notion that clinical studies have often been set up with unbalanced study populations, typically including more males than females. Therapies that work in men, may therefore lead to suboptimal outcomes in females. It has also been shown that some drugs may lead to fatal arrhythmia in females, while the risk is much lower in males. In addition, diagnostic critera often do not take into account differences between the male and female cardiovascular system, such as, for instance, the thickness of the wall of the ventricle to classify ventricular hypertrophy. When using the same cut-off value for males and females, the female heart - ususally starting off from a lower value - has progressed further in the (mal)adaptive process than the typical male heart. As such, women may receive treatment later in their disease process than men, leading to worse outcome of treatment. 

A disease with a striking difference in prevalence in males and females is the so-called heart failure with preserved ejection fraction (HFpEF), where the thickened left ventricle contracts seemingly normal with an adequate emptying of the heart, but has an abnormal relaxation, necessitating elevated filling pressure with congestion of the lungs, leading to typical symptoms of heart failure with shortness of breath. Together with prof. Peirlinck at TU Delft and prof. Chirinos at the University of Pennsylvania, we want to get a deeper understanding of the pathophysiology of HFpEF in males and females through biomechanical modelling. It is believed that in HFpEF, the coupling of the heart with the arterial tree plays a key role in the pathophysiology.

 


Doelstelling:

The aim of this thesis is to use insights from literature and available data in healthy subjects and in patients to set up sex-specific biomechanical models of the heart and circulation that account for heart-arterial interaction and that also encompass the growth and remodelling of the tissues of the heart and arteries. These models can range from fairly simple 0D models of the circulation shown in the figure below, to full-blown 3D cardiac models as can be found on the website of prof. Peirlinck. Besides biomechanical modelling and depending on the interest of the student, the thesis may include machine learning, statistical shape modelling and/or uncertaintly quantification.