Baroreflex sensitivity with different lags and random forests for staging cardiovascular autonomic neuropathy in...

Impaired baroreflex sensitivity (BRS) may indicate cardiovascular autonomic neuropathy (CAN), which often remains undiagnosed during the initial course of diabetes mellitus. The baroreflex mechanism can be considered negative feedback because of baroreflex delay, the time delay between a change in blood pressure and the counteracting heart rate response. This work sought to analyze BRS considering lags from 1 to 10 RR intervals. We hypothesized that diabetic patients with subclinical CAN (SCAN) have a detectable delay in autonomic nervous system activity and that this would differ from patients without CAN (NCAN) and with established CAN (ECAN). In the first stage, 30 patients were included in an exploratory analysis using the Principal Component Analysis. Six indexes related to the BRS delay were proposed and considered significant for staging diabetic patients. Three indexes allowed for the differentiating of patients with and without CAN, and three indexes distinguished subjects with SCAN from subjects with NCAN or ECAN. Then, in the second stage, a random forest model was developed with 72 subjects, using the variables selected in the first stage. It was possible to detect SCAN, and to point out those subjects with the potential to change the CAN stage, allowing for the tracking of CAN progression. The model achieved a sensitivity of 96% and specificity of 100% to detect SCAN. Thus, the BRS analysis considering delayed reaction in the dynamics of heart rate variability may contribute to an accurate screening tool to staging CAN, in addition to indicating patients with most insidious disease progress.