Biophysical Characterization of the Underappreciated and Important Relationship Between Heart Rate Variability and Heart Rate

Abstract

Heart rate variability (beat-to-beat changes in the RR interval) has attracted considerable attention over the last 30+ years (PubMed currently lists >17,000 publications). Clinically, a decrease in heart rate variability is correlated to higher morbidity and mortality in diverse conditions, from heart disease to foetal distress. It is usually attributed to fluctuation in cardiac autonomic nerve activity. We calculated heart rate variability parameters from a variety of cardiac preparations (including humans, living animals, Langendorff-perfused heart and single sinoatrial nodal cell) in diverse species, combining this with data from previously published papers. We show that regardless of conditions, there is a universal exponential decay-like relationship between heart rate variability and heart rate. Using two biophysical models, we develop a theory for this, and confirm that heart rate variability is primarily dependent on heart rate and cannot be used in any simple way to assess autonomic nerve activity to the heart. We suggest that the correlation between a change in heart rate variability and altered morbidity and mortality is substantially attributable to the concurrent change in heart rate. This calls for re-evaluation of the findings from many papers that have not adjusted properly or at all for heart rate differences when comparing heart rate variability in multiple circumstances.

After-exercise heart rate variability is attenuated in postmenopausal women and unaffected by estrogen therapy

“…In contrast to these findings in premenopausal women, in postmenopausal women; 2) HF and LF remained suppressed below pre-exercise values at one hour post acute exercise; and 3) pre-treatment with chronic oral estrogen did not augment vagal modulation at rest, or enhance HRV recovery in the post-exercise period, suggesting delayed recovery of autonomic modulation. In view of recent concerns that these indices of HRV are simply a function of HR 25 , it is important to emphasize that these differences between premenopausal and postmenopausal women occurred despite identical heart rates after exercise.…”

Langendorff's isolated perfused rat heart technique: a review

“…Both systems, the constant hydrostatic pressure system and the constant flow system, do not normally permit the heart to generate pressure-volume work. 22 In both cases, this retrograde flow shuts the leaflets of the aortic valve so that the perfusion solution cannot enter the left ventricle. As mentioned above, most parts of the apparatus for Langendorff's heart perfusion are water-jacketed with warm circulating water to maintain the temperature of the perfusate and of the heart at constant temperature of 37°C.…”

“…Various other electrodes which can be used include a suction, wick, and sewn-on contacts. 7,21,22 Cardiac contractile function and coronary flow are generally studied simultaneously. Any change in coronary flow also affects the contractility of the heart.…”

Letter by Monfredi et al Regarding Article, “Physical Activity and Heart Rate Variability in Older Adults: The Cardiovascular Health Study”

“…Furthermore, there are no details of how HRV was corrected for differences in HR; we assume they made a linear correction, which will be inadequate to correct for the nonlinear dependence of HRV on HR. 3 The importance of HR on observed changes in HRV can be estimated: Zaza et al 4 have independently shown that the natural log of standard deviation of normal-to-normal beats-log n (SDNN)-changes by 0.16 to 0.17 for every 10 beats per minute (bpm) change in HR; our own data yield a similar value. Figure 2) could be explained by a modest and plausible bradycardia (5.7 bpm decrease in the example given).…”

“…2 It is established that time-and frequency-domain measures of HRV are nonlinearly dependent on HR, with low HRV being intrinsically linked to a higher HR, and vice versa. [3][4][5] We argue that HRV is a nonlinear surrogate of HR. Soares-Miranda et al recognized the dependence of HRV on HR, and stated that HR was evaluated as a "potential confounder or mediator" of HRV in a separate analysis by "adding a multiplicative interaction term and assessing the statistical significance of the Wald test".…”