Tracking Acoustic and Electrophysiological Changes Associated with CKD-induced Cardiac and Valvular Remodeling in a Mouse Model

Abstract

Objective: Patients with chronic kidney disease (CKD) are at a higher risk of developing heart and valvular diseases than the general population. Non-invasive screening methods are needed to identify cardiovascular abnormalities in this population. In this study, we use a diet-induced CKD mouse to study AV and cardiac remodeling. We hypothesize that structural differences in AV and cardiac remodeling occur in CKD mice, and can be identified through phonocardiogram (PCG) and electrocardiogram (ECG) signals. Methods: Eight-week old C57BL/6J mice were assigned to the following groups: 1) control group, fed a normal chow diet for 12 weeks, and 2) CKD group, fed a chow containing 0.2% adenine, with normal (0.6%) phosphorus for 6 weeks to induce CKD, and 3) CKD+high phosphate (HP) group, fed CKD inducing diet for 6 weeks, and then fed for 6 weeks with a 0.2% adenine/1.8% phosphorus diet to induce cardiovascular calcification. PCG and ECG signals were recorded weekly and echocardiogram parameters were recorded at the experimental end-point. Results: The HP diet induced aortic valve calcification in the CKD+HP group. CKD and CKD+HP group had increased end-diastolic volume, which is indicative of left ventricular hypertrophy. Changes in ECG parameters indicate that CKD groups have delayed cardiac repolarization time, an early ECG marker associated with arrhythmias. PCG signals indicate the presence of a systolic and diastolic murmur in the CKD+HP group, a characteristic of both valve disease and cardiac dysfunction. Conclusions: We demonstrate that the diet-induced CKD mouse model can be used to study valve and cardiac remodeling, and ECG and PCG signals can noninvasively track valve and cardiac changes. Future studies will determine the adequacy of using these signals to predict cardiovascular diseases.