# Impact of Heart Rate Fragmentation on the Assessment of Heart Rate Variability +
## 1 Introduction  
The analysis of heart rate variability (HRV) is widely used for assessing autonomic function. Particularly, the high-frequency component (HF, 0.15-0.4 Hz) of HRV is currently the most popular metric of cardiac vagal function (Figure 1). The association between HF and cardiac vagal function is supported by the fact that respiratory sinus arrhythmia (RSA), the major source of the HF, is mediated purely by the cardiac parasympathetic nerves [1].  
However, there are two unanswered questions about HF. The first question is the paradoxically low predictive power of HF for mortality risk after acute myocardial infarction (Figure 2) [2]. Decreased HRV is increased mortality risk after acute myocardial infarction [3], but the predictive power of HF is lowest among HRV frequency components. Why is the predictive power of HF such low, despite the fact that the association of decreased HRV with mortality risk has been explained as cardiac parasympathetic dysfunction? The second question concerns the paradoxical increase in HF in the elderly (Figure 3) [4]. Cardiac parasympathetic function is believed to decrease with advancing age, but big data studies have reported that HF power increases paradoxically and progressively from age 75. Why?Figure 1: Analysis of heart rate variability (HRV) under sinus rhythm. HF = high-frequency component (0.15–0.4 Hz), LF = low-frequency component (0.04–0.15 Hz), PSD = power spectral density.  
Figure 2: Relative risk of death predicted by the decrease in HRV frequency components. L/H = LF to HF ratio in power, TP = total power, ULF = ultra-low-frequency component (<0.003 Hz), VLF = very-low-frequency component (0.003–0.04 Hz). Made from Table 2 in reference [2].  
An answer to these questions may be the influence of heart rate fragmentation (HRF) [5; 6; 7]. While other HRV components are mediated by fluctuations in autonomic activity, HRF is thought to be a heart rate fluctuation intrinsic to the heart itself [8]. They usually appear in or above the HF band. This phenomenon has been known for a long time and called with several terms including complex HRV [9; 10], sinus node alternans [11], erratic sinus rhythm [12; 13], and heart rate fragmentation [5; 6; 7]. HRF is a type of sinoatrial instability characterized by frequent (often every beat) appearance of peak and valley in R-R interval time series despite ECG appealing normal sinus rhythm (Figure 4).  
Because the assessment of parasympathetic function by HRV depends on the assumption that RSA is only source of the HF, HRF that is measured as a part of HF confounds the parasympathetic functional assessment by HRV (Figure 5). However, neither the factors affecting the occurrence of HRF nor the degree of its impact on the HF power has been clarified. In this study, we analyzed the age and sex dependency of the occurrence of HRF and the degree of the influence on HRV metrics using 24-h ECG big data of the Allostatic State Mapping by Ambulatory ECG Reposit  
Figure 4: ECG and R-R intervals showing heart rate fragmentation (HRF). Although ECGs look like sinus rhythm (upper and middle panels), R-R interval trend gram shows periodic dip (lower panel).  
Figure 3: Age-dependent changes in HRV frequency components. Made from data from a previous study [4].