Wearable Patch Heart Rate Variability Is an Early Marker of Systemic Inflammation During Experimental Human Endotoxemia

Early diagnosis and treatment can reduce the risk of organ failure and mortality in systemic inflammatory conditions. Heart rate variability (HRV) has potential for early identification of the onset of systemic inflammation, as it may detect changes in sympathetic nervous system activity resulting from the developing inflammatory response before clinical signs appear. With the use of new methodologies, we investigated the onset and kinetics of HRV changes as well as several inflammatory parameters and symptoms during experimental human endotoxemia, a model of systemic inflammation in humans in vivo.Healthy volunteers were intravenously administered LPS (n = 15) or placebo (n = 15). HRV was determined using a wireless wearable device, and parameters low to high frequency (LF:HF) ratio, root mean square of the successive differences (RMSSD), and standard deviation of normal-to-normal R-R intervals (SDNN)were calculated through 1-min-rolling 6-min windows. Plasma cytokine levels and flu-like symptoms and vital signs were serially assessed.The increase in LF:HF ratio, reflecting sympathetic predominance, was more pronounced in the LPS group compared to the placebo group, with the difference becoming statistically significant 65 min following LPS administration (1.63 [1.42-1.83] vs. 1.28 [1.11-1.44], P = 0.005). Significant between-group differences in RMSSD and SDNN were observed from 127 to 140 min post-LPS administration onwards, respectively. Plasma cytokine levels showed significant between-group differences staring 60 min post-LPS. For symptom score, heart rate, temperature, and diastolic blood pressure, significant differences compared with the placebo group were observed at 90, 118, 120, and 124 min post-LPS, respectively.In a controlled human model of systemic inflammation, elevations in the LF:HF ratio followed very shortly after elevations in plasma cytokine levels and preceded onset of flu-like symptoms and alterations in vital signs. HRV may represent a promising non-invasive tool for early detection of a developing systemic inflammatory response.