# Impact of Heart Rate Fragmentation on the Assessment of Heart Rate Variability +
## 4 Discussion
They also reported that the degree of HRF was greater in the cardiac patients than in the healthy subjects. Although our observations of increased PIPh and Wh3 in the elderly are consistent with those of [PERSON] et al. [5; 6], the present study also delineated the entire picture of age and sex dependency and the impact of HRF on HRV metrics. In the present study, we observed a negative correlation between PIPh and PIPs (Table 2). Also, while PIPh showed positive correlations with LF and HF in all age groups, PIPs showed strong negative correlations with LF and HF (Table 3). These indicate that the HRF metric shows the opposite behavior depending on the definition of the inflection point. Although the soft inflection point is defined as the point at which a change in consecutive NN intervals is preceded or followed by unchanged consecutive NN intervals, even changes in consecutive NN intervals if they were below the detection threshold determined by ECG sampling frequency are not detected and are judged unchanged. Conversely, if the change exceeds the threshold, the points that had been defined as a soft inflection point could change to a hard inflection point or a non-inflection point. Therefore, increasing the amplitude of HRF could increase the points where the judgment changes from soft to hard, creating a complementary relationship between PIPs and PIPh. Similarly, increasing the amplitude of LF and HF could increase the points where the judgment changes from soft to non-inflection, creating negative correlations between PIPs and these HRV metrics. Although PIPs may help characterize the dynamic features of NN interval inflections, PIPs itself does not seem to be a measure of the degree of fragmentation, i.e., HRF. Due to the cross-sectional nature of this study, the causal links between changes in HRF and HRV metrics are not completely clear. In short, the increase in PIPh and Wh3 in the elderly could be the result of increased HF, although this is not consistent with weak correlations between PIPh and HF before age 20. Additionally, aging is accompanied by degenerations of the regulatory network, which has been thought to reduce physiological parasympathetic modulations, such as those controlling heart rate. This is expected to reduce HF and other short-term HRV metrics. Thus, the counterintuitive increase in HF in the elderly seems to be the result but not the cause of increased HRF. Several mechanisms can be considered for the genesis of HRF [5], which include sinus node exit block, subtle atrial bigeminy originating near or within the sinoatrial (SA) node, modulated SA node parasystole caused by multiple interacting pacemaker sites in the SA node [16], and modulated periodicity of pacemaker clock in the SA node [17; 18]. Thus, increased HRF may be a marker reflecting the age-related degeneration or pathologic impairment of the SA-node-atrial network for cardiac pacemaker function. Increased HRF in patients with coronary artery disease [5] and its association with adverse cardiovascular events [7] support this contention. Although it is interesting if HRF itself also plays a proarrhythmic role, particularly in the development of atrial fibrillation, it remains to be clarified. Increasing HRF with age is thought to confound autonomic functional assessment by HRV and to dilute the association between decreased HRV and increased risk for adverse prognosis in the elderly [8]. The principle of the assessment of parasympathetic function by HRV depends on the assumptions that HRV above 0.15 Hz (including HF band) is mediated solely by the cardiac parasympathetic nerve [1] and that HRV in this band is mediated by respiratory fluctuation of autonomic outflow to the sinus node [19; 20; 21; 22]. In the presence of HRF, however, both assumptions may not hold. HFR causes non-autonomous, non-respiratory HRV in the frequency band, well above 0.15 Hz. The HRV that the HRV causes at frequencies of 0.15 to 0.4 Hz is integrated as HF power and leads to an overestimation of parasympathetic function.