An in-vitro model of stiffened aortic valves to develop an iso-stiffness-lines graph for severity evaluation aortic stenosis

Abstract

Abstract Introduction The echocardiographic diagnosis of aortic stenosis (AS) is established by assessing its maximal opening area (OA). The behavior of OA is dependent on transvalvular flow which can be low in case of low-flow, low-gradient AS. However, current guidelines for the assessment of AS do not consider flow but rather a stroke volume. This experiment was designed to create a graphical representation of the OA versus flow for various valve stiffness values to eventually build a model with iso-stiffness lines. Methods We filmed harvested porcine aortic valve mounted in a pulsatile flow loop during the ejection time with a high speed camera (2000Hz), measured for each time point OA and the instantaneous flow through the aortic valve at 10 different mean flow rates (ranging from 0.5 to 5.0 liters/min) and divided both, OA and flow, by the area of left ventricular outflow tract (LVOT) in order to account for different valve sizes. We plotted each OA against its corresponding flow after correcting for the intersignal delay. Due to a time lag between flow onset and the valve opening caused by a ballooning of the valve, we only included the points corresponding to the 5% highest instantaneous flow rates (for each of the 10 mean flow rates). We stiffened the valve by treating it with a protein cross-linking agent (formaldehyde) to yield a total of three stiffness grades (a, b, c) and repeated the procedure for each of those grades. Results We generally observed an asymptotic appearance of the flow-OA relationship as well as a flattening of this relationship with increasing valve stiffening. This visually matches well simulated data generated with a sigmoid model. Conclusions We could obtain all flow/OA pairs at different stiffness grades. This will allow us to fit a sigmoid function capturing the flow-OA relationship for each stiffness grade and create iso-stiffness line that will allow classifying valve stenosis grade irrespective of the flow and the size of the valve in one single graph, potentially simplifying the grading system of aortic stenosis, especially for patient with low-flow, low-gradient AS. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Bern Center for Precision Medicine (BCPM) Stiffness stage 1All stiffness stages combined