# Impact of Heart Rate Fragmentation on the Assessment of Heart Rate Variability +
## 4 Discussion  
HRF is a type of sinus arrhythmia that should be noted as a potential factor confounding autonomic function evaluation and prognosis prediction by HRV [8], but the factors affecting the occurrence of HRF and the degree of its impact on HRV has been unclear. In the present study, we examined the age and sex dependency of HRF and its impact on HRV metrics using the ALLSTAR database of clinical 24-h Holter ECG big data. We quantified HRF with two types of metrics (PIP and symbolic dynamics word category) concerning the inflection pattern (hard and soft) in NN interval time series. Analysis of 24-h ECG samples with even distribution for all ages (0-100 year) for both genders revealed that the HRV metrics reflecting higher frequency oscillations (rMSSD, LF, HF, and VHF) showed a paradoxical increase after age 75 and that the increase was more pronounced the higher the frequency band (LF < HF < VHF). The similar age dependent changes were observed in the HRF metrics quantifying the occurrence of hard NN interval inflection (PIPh and Wh3), while those quantifying the occurrence of soft inflection (PIPs andWs2 andWs3) showed the almost opposite patterns of age dependent change. Additionally, among HRV metrics, age-adjusted HF and VHF were greater in women than in men, and age-adjusted PIPh was also greater in women than in men. Consistent with these, negative correlations were observed between PIPh and PIPs and between word categories reflecting hard and soft inflection points. Both LF and HF power correlated positively with PIPh and negatively with PIPs. The correlation coefficients between HF power and PIPh, however, exceeded 0.50 only at ages 60-90, indicating that HRF has a large impact (>25% of the variance) on individual difference in HF power in this age range. Although the term HRF was first proposed in 2017 by [PERSON] et al. [5], this phenomenon has long been known in several terms [9; 10; 11; 12; 13]. Although HRF is a type of HRV that is defined as the cardiac beat-to-beat cycle length variation of sinus nodal rhythm, HRF has a fundamental difference from conventional HRV. In contrast to conventional HRV that is caused by the physiological modulation of the cardiac intrinsic pacemaker rate through autonomic input to the sinus node, HRF is the pathological variation of the intrinsic pacemaker rate itself, although the occurrence of HRF may be triggered and its nature may be modified by the autonomic input [6]. \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Age**} & \multirow{2}{*}{**N**} & \multicolumn{2}{c}{**PIPh**} & \multicolumn{2}{c}{**PIPs**} \\ \cline{3-6}  & & **LF** & **HF** & **LF** & **HF** \\ \hline
0 & 181 & 0.40 & 0.25 & \(-\)0.55 & \(-\)0.54 \\
5 & 200 & 0.25 & 0.08 [FOOTNOTE:]Footnote : All correlation coefficients (except those marked with NS) were statistically significant. Only those greater than 0.50 were presented in bold face. The variables are explained in Table 1 and caption of Figure 7.[ENDFOOTNOTE] & \(-\)0.50 & \(-\)0.42 \\  
\hline \hline \end{tabular}
\end{table} 
Table 3: Correlation coefficients between HRF and HRV metrics. Earlier studies reported the potential clinical significance of HRF. [PERSON] et al. reported a complex pattern of R-R interval Poincare plots that is thought to correspond to a type of HRF in patients with advanced heart failure [9] and its association with serum norepinephrine level in 27 patients [10]. [PERSON] et al. defined erratic sinus rhythm as the pattern of Poincare plots with numerous plots outside an ellipsoid or comet-shaped core and the pattern of HRV FFT spectrum with increased power in band \(>\)0.4 Hz (VHF in the present study) [12; 13]. They reported that this pattern was associated with increased mortality risk after myocardial infarction. [PERSON] et al. [5; 6] reported that the degree of fragmentation measured as PIP and other HRF metrics increased with age in 202 ostensibly healthy subjects and in 271 patients with coronary artery disease.