Abstract
Background: Short-term heart rate variability (HRV) is most commonly attributed to physiologic vagal tone modulation. However, with aging and cardiovascular disease, the emergence of high short-term HRV, consistent with the breakdown of the neuroautonomic-electrophysiologic control system, may confound traditional HRV analysis. An apparent dynamical signature of such anomalous short-term HRV is frequent changes in heart rate acceleration sign, defined here as heart rate fragmentation.Objective: The aims were to: (1) introduce a set of metrics designed to probe the degree of sinus rhythm fragmentation; (2) test the hypothesis that the degree of fragmentation of heartbeat time series increases with the participants' age in a group of healthy subjects; (3) test the hypothesis that the heartbeat time series from patients with advanced coronary artery disease (CAD) are more fragmented than those from healthy subjects; and (4) compare the performance of the new fragmentation metrics with standard time and frequency domain measures of short-term HRV.Methods: We analyzed annotated, open-access Holter recordings (University of Rochester Holter Warehouse) from healthy subjects and patients with CAD using these newly introduced metrics of heart rate fragmentation, as well as standard time and frequency domain indices of short-term HRV, detrended fluctuation analysis and sample entropy.Results: The degree of fragmentation of cardiac interbeat interval time series increased significantly as a function of age in the healthy population as well as in patients with CAD. Fragmentation was higher for the patients with CAD than the healthy subjects. Heart rate fragmentation metrics outperformed traditional short-term HRV indices, as well as two widely used nonlinear measures, sample entropy and detrended fluctuation analysis short-term exponent, in distinguishing healthy subjects and patients with CAD. The same level of discrimination was obtained from the analysis of normal-to-normal sinus (NN) and cardiac interbeat interval (RR) time series.Conclusion: The fragmentation framework and accompanying metrics introduced here constitute a new way of assessing short-term HRV under free-running conditions, one which appears to overcome salient limitations of traditional HRV analysis. Fragmentation of sinus rhythm cadence may provide new dynamical biomarkers for probing the integrity of the neuroautonomic-electrophysiologic network controlling the heartbeat in health and disease.
Highlights
Heart rate variability (HRV) in healthy subjects, over short time scales, is primarily attributable to fluctuations in vagal tone
The most recognizable manifestation of this parasympathetic influence is the oscillatory Cardiac interbeat interval (RR) interval pattern (Figure 1) termed respiratory sinus arrhythmia (RSA) that results from the coupling between breathing and heart rate (Angelone and Coulter, 1964; Hirsch and Bishop, 1981; HRV, 1996; Stauss, 2003)
This topic is of particular importance because parasympathetic regulation of sinus rhythm decreases with aging and organic heart disease (HRV, 1996; Kuo et al, 1999; Thayer et al, 2010)
Summary
Heart rate variability (HRV) in healthy subjects, over short time scales, is primarily attributable to fluctuations in vagal tone. A central interpretative framework underlying contemporary HRV analyses is one in which the degree of short-term variability of normal-to-normal (NN) sinus beats is used as a dynamical biomarker of cardiac vagal tone modulation (HRV, 1996; Billman, 2011) This topic is of particular importance because parasympathetic regulation of sinus rhythm decreases with aging and organic heart disease (HRV, 1996; Kuo et al, 1999; Thayer et al, 2010). In the “extreme” case of sinus alternans, the sign of heart rate acceleration changes every beat (Lewis, 1920; Geiger and Goerner, 1945; Friedman, 1956; Binkley et al, 1995) The presence of these abnormal variants of sinus rhythm limits the utility of traditional HRV analysis, since an increase in the overall amount of short-term variability can no longer be solely attributed to enhanced vagal tone modulation. An apparent dynamical signature of such anomalous short-term HRV is frequent changes in heart rate acceleration sign, defined here as heart rate fragmentation
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