Abstract

Introduction: Heart valve diseases (HVDs) often remain undiagnosed until late stages, especially in underserved populations, leading to significant comorbidities. Artificial intelligence has improved murmur detection in digital phonocardiograms (PCG). However, the presence of murmurs depends on hemodynamic factors unrelated to HVD. Screening tests that directly measure features of valvular remodeling regardless of symptoms would improve HVD diagnosis. We used a mouse model of chronic kidney disease (CKD) induced aortic valve (AoV) remodeling to determine whether S2 sound changes can be used to detect early stages of AoV calcification. Methods: Eight-week old C57BL/6J mice (n=24) were assigned the following diets for 12 weeks: 1) control group fed a normal chow diet, 2) CKD group fed an adenine-supplemented diet to induce CKD, and 3) CKD+HP group fed the CKD diet for 6 weeks, then an adenine and high phosphate (HP)-supplemented diet for another 6 weeks to induce AoV calcification. PCG signals were recorded every 6 weeks. Endpoint AoV calcification and echocardiogram measures of valvular function were assessed. We developed a clustering method based on time domain principal component analysis of S2 sounds collected at week 6 (W6) to classify week 12 (W12) S2 sounds and identify S2 sound alterations due to HP. Results: The high phosphate diet induced AoV calcification in CKD+HP mice (1a). Of the total number of S2 sounds per mouse, an average of 84.18% and 81.15% S2 sounds (1b and 1c) were accurately classified as control or CKD mice with a specificity and sensitivity of 90.91% and 100%, respectively. CKD+HP mice had an average of 59.22% W12 S2 sounds that neither classified as control nor CKD. Conclusions: Mice that have AoV calcification show distinct S2 sounds features that were absent in the control and CKD groups. In this study, we demonstrate the feasibility of using the S2 sound not only to detect AoV calcification prior to expected hemodynamic changes but also to detect CKD.

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