The importance of stimuli and response in non-invasive endothelial dysfunction

Abstract

Endothelial dysfunction has been identified as the most significant predictor of a major adverse cardiovascular event (MACE).^1–2 
Although the focus is generally on physiological response, and the associated arterial flow and biomechanics metrics, information associated with hemodynamics and stimulus at the fluid-intimal surface also provides valuable information. Although cumulative shear is the stimulus present leading to the resultant metrics representing the degree of endothelial dysfunction, many platforms have a significant subjective error. The current gold standard is considered to be flow-mediated dilatation (FMD), where the coefficient of variation ranges from 10% to 50%. A recent technology based on a technique called calibrated cuff plethysmography (CCP) has demonstrated a CV of 15.33%. The Cordex SmartCuff is based on CCP principles and has demonstrated statistical significance to multiple accepted metrics used to predict cardiovascular disease with p values ranging from .01 to .0001. One key difference between FMD and CCP/Cordex SmartCuff is that where FMD provides a measured arterial change in diameter at room standard pressure conditions, the CCP/Cordex SmartCuff technique provides a calibrated measurement of arterial compliance in normal and hyperemic conditions across the entire transmural pressure range from full collapse to fully open. Additionally, a bench model called the surrogate arm has demonstrated that subclinical atherosclerosis, the earliest stage of cardiovascular disease, could be quantified using the fluid mechanics metric relative roughness. Three silicone artery phantom groups were created with different degrees of inner diameter surface roughness to explore a relationship between relative roughness and sound associated with fluid flow. Power spectral density graphs show that there is a difference in frequency response between a smooth and rough artery phantom at the same flow rate, providing preliminary support that a sound analysis of fluid flow could provide information regarding early-stage cardiovascular disease. Non-invasive endothelial dysfunction measurement could prove valuable in improving long COVID patient outcomes, where a relationship exists between cardiovascular disease and COVID-19 metrics. Increased knowledge of hemodynamic responses and the relationship with the stimulus at the intimal surface provides key information toward early detection of endothelial dysfunction that could improve clinical outcomes and develop better micromanufactured cardiovascular devices.