Impact of hypertension on mean transvalvular gradients in aortic stenosis Lessons learned from in silico modelling
Authors: Liebenberg J J , Doubell A F , Laubscher R , Herbst P G 
Published: November 2023

Abstract

Introduction
The influence of hypertension on the diagnostic assessment of aortic stenosis (AS) severity is unclear, yet clinically relevant. To clarify the effect of hypertension on transvalvular gradients, requires a better understanding of the impact that blood pressure change has on mean flow rate. Also, the effect of various degrees of AS severity, the valve geometry and intrinsic left ventricular contractile function (elastance) on this interaction, needs to be clarified. Existing clinical research on this topic is limited by not incorporating the full complement of factors that influences the directionality and magnitude of mean transvalvular gradient change for any given change in blood pressure.

Purpose
To use validated flow dynamics modelling grounded in fundamental physics principles to create a digital platform where various parameters can be manipulated to quantify the effects of bloodpressure change on mean transvalvular gradients in various pathological states.

Methods
A validated, zero-dimensional electro-hydraulic analogue computer model of the human cardiovascular circulatory system was generated. It was used to assess the impact of blood pressure changes on left ventricular pressure and transvalvular gradients at various flow rates, left ventricular elastances, a range of aortic valve areas and for different aortic valve morphologies.

Results
Mean transvalvular gradients are flow dependent. The impact of hypertension on mean flow rate (MFR), and hence on mean gradient (MG), is influenced by the aortic valve area as well as the underlying left ventricular elastance (Figure 1). Subsequently, the relationship between MFR and MG could be modelled (Figure 2). Generally, for a given change in systemic arterial pressure, the impact on MG will be the most marked for lower flow rate states such as is expected in more severe degrees of AS and for worse intrinsic left ventricular (LV) contractility. Furthermore, for a constant hemodynamic valve area, the hydraulic valve orifice area was found to be smaller in rheumatic AS compared to degenerative AS. This results in less susceptibility to blood pressure induced changes in mean transvalvular gradient. Similarly, the size of the aortic root was found to be inversely related to the susceptibility to induce a change in mean gradient for a change in blood pressure.

Conclusion
The interaction between hypertension and mean gradients in AS is complex. The current work places previous recommendations in perspective by quantifying the magnitude of the effect that a change in blood pressure has on mean gradient in various pathophysiological states. By doing so it provides more granularity into this multifaceted interaction compared to previously oversimplified deductions from clinical studies. The findings of this study creates a basic science framework based on first principles that dictates the scope of parameters that should be considered in future clinical research on the topic.Modelling 1Modelling 2