Validation of ultra-short-term (10-second) RMSSD for dynamic tracking of parasympathetic tone
W Garvin, N Makmal, B Nearing, S C Schachter, R L Verrier, T D PangAbstract
Background
Patients with chronic epilepsy exhibit an "Epileptic Heart Syndrome" characterized by autonomic imbalance and depressed vagal tone. The time-domain heart rate variability (HRV) measure, root mean square of successive differences (RMSSD), reflects parasympathetic nervous system (PNS) modulation of the heart on a beat-by-beat basis. However, standard 5-minute RMSSD windows lack the temporal resolution to track rapid autonomic fluctuations, such as during acute epileptic seizures.
Purpose
To validate the accuracy of ultra-short-term (10-second) versus standard 5-minute RMSSD windows in assessing dynamic autonomic changes in patients with epilepsy.
Methods
Continuous ECG recordings from 35 patients undergoing multi-day continuous video EEG monitoring were analyzed during seizure-free baseline periods. For each patient, resting RMSSD values were calculated concurrently using 10-second and 5-minute sliding windows over a 1-hour period on hospital day 2. Agreement was assessed using Lin’s Concordance Correlation Coefficient (CCC) with 95% confidence intervals (CI). Differences in means and interquartile ranges (IQR) were compared using two-sided and one-sided Wilcoxon signed rank tests, respectively. Tolerance analysis accounting for proportional bias was performed to calculate the 95% prediction interval (PI) with 95% tolerance limits (TL).
Results
Study participants (mean age 42.8 ± 17.6 years, 62.9% female, 80% with confirmed epilepsy) and an average heart rate of 76.4 ± 11.1 beats per minute. There was no significant difference in the 1-hour mean RMSSD between the 10-second window (31.9 ± 22.4 ms) and 5-minute window (32.1 ± 21.1 ms), (p=0.27) (Figure 1). Agreement between the two methods was high with a CCC of 0.997 (95% CI: 0.994 to 0.998) and a mean within-patient difference of 1.2 ms, with 80% of differences <2 ms. The predicted mean difference ranged from 1.3 (95% CI: 0.7 to 2.0) to 4.1 (95% CI: -2.3 to -5.8) for low and high RMSSD values, respectively. For low RMSSD values, the 95% PI ranged from 4.2 to -1.5 (95% TL: 5.1 to -2.4) whereas the 95% PI for high RMSSD values ranged from -0.8 to -7.3 (95% TL: 1.0 to -9.3), as illustrated in Figure 2. The average IQRs of the 10-second window were significantly larger than the 5-minute window (13.54 ± 8.76 ms vs 6.31 ± 3.66 ms, respectively (p<0.0001).
Conclusion
Ultra-short-term (10-second) RMSSD is an accurate measure of parasympathetic tone, demonstrating high within-patient agreement with the conventional 5-minute standard. Its high temporal resolution for measuring dynamic beat-to-beat changes offers a distinct advantage over the traditional method and represents a powerful tool for assessment of acute events like epileptic seizures. This methodology has direct applicability in cardiology and enables real-time assessment of dynamic autonomic nervous system function during acute cardiac events, such as acute myocardial ischemia and decompensated heart failure.Comparison of 2 RMSSD window averagesBland-Altman Plot of RMSSD Comparison