Deceleration Capacity of Heart Rate After Acute Altitude Exposure

Introduction

The autonomic nervous system plays a crucial role in adaptive changes after high-altitude exposure. Assessment of heart rate variability (HRV) provides insights into regulations of the cardiac autonomic nervous system. There are a number of studies investigating the dysregulation of the autonomic nervous system after exposure to high altitude using HRV parameters. Most studies assume a reduction in parasympathetic and an increase in the sympathetic activity at high altitude (Kanai et al., 2001; Boos et al., 2017). These changes tend to reverse with acclimatization after 6 days (Cornolo et al., 2004). A few of the studies have linked alterations of the autonomic nervous system with the symptoms of acute mountain sickness (AMS) (Karinen et al., 2012; Yih et al., 2017), or tried to predict AMS by distinct changes of HRV measures under normobaric normoxic conditions (Sutherland et al., 2017). However, results of studies on HRV changes after high-altitude exposure are inconsistent, and HRV alterations are mostly detectable at altitudes only far above 3000 m.

Deceleration capacity (DC) of heart rate is an advanced and robust marker of HRV that is considered to predominantly reflect the vagal activity of the cardiac autonomic nervous system. DC is an integral measure of all deceleration-related oscillations of heart rate, including regulations in the very low-frequency, low-frequency (LF), and high-frequency (HF) bands, depending on the recording time (Bauer et al., 2006a; Rizas et al., 2017). In previous studies, the prognostic value of impaired DC in predicting late mortality after myocardial infarction exceeded that of abnormal standard measures of HRV (Bauer et al., 2006a; Rizas et al., 2017).

In this study, we aimed to investigate alterations of DC after altitude exposure and to compare the results with standard measures of HRV.

Methods

Assessment of DC and HRV parameters

ECG raw signals were preprocessed by an experienced technician. Heart rate, DC, and standard parameters of HRV were assessed according to previously published technologies using customized software (Bauer et al., 2006a). DC is based on a novel mathematical signal analysis method (phase-rectified signal averaging, PRSA), which transforms complex time series (i.e., heart rate recordings) in a significantly shorter signal. To calculate DC in a first step, heartbeat intervals longer than the preceding interval are defined as decelerating anchors. In a second step, segments around anchors are defined, aligned at the anchors (phase rectification) and averaged (signal averaging) to obtain PRSA-signal. The central part of the PRSA signal is quantified by wavelet analysis to obtain the numerical measure of DC (Fig. 1A, B). Using short-term recordings (30 minutes), DC ≤2.5 ms is considered to be abnormal as it indicates increased mortality risk in postinfarction patients (Rizas et al., 2017).

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FIG. 1.

Typical phase-rectified signals (A) at baseline (521 m altitude) and (B) after acute altitude exposure (2650 m altitude). After acute altitude exposure, the amplitude of the phase-rectified signal is significantly lower than baseline levels. i = index of phase-rectified signal averaging signal X(i). (C) The diagram shows the mean deceleration capacity levels at baseline, T1 and T2. T1, immediately after high-altitude exposure; T2, after a sojourn of 24 hours at high altitude.

The following standard measures of HRV were assessed: standard deviation of all NN intervals; estimate of overall HRV, the square root of the mean of the sum of the squares of differences between adjacent NN intervals; estimate of short-term components of HRV, and HRV index (total number of all NN intervals/maximum of the sample density distribution; estimate of overall HRV). As spectral components, we calculated LF and HF components and their ratio (LF/HF) from ECG recordings.

Results and Discussion

DC at baseline was 10.2 ± 0.8 ms and decreased significantly to 8.9 ± 1.0 ms (p < 0.05) after acute altitude exposure. After a sojourn of 24 hours in the high-altitude environment, DC remained low at 8.6 ± 3.4 ms (Fig. 1). This significant decrease of DC levels after acute altitude exposure is consistent with an acute withdrawal of vagal activity. The decrease of vagal activity contributes to the dysbalance of the cardiac autonomous nervous system that has been described previously (Kanai et al., 2001).

None of the individuals had a DC ≤2.5 ms that is considered as high risk in patients after myocardial infarction (Bauer et al., 2006a). In one study subject, DC decreased <4.5 ms after altitude exposure, a measure considered as intermediate risk in patients after myocardial infarction if it would persist >24 hours (Bauer et al., 2006a; Rizas et al., 2017). However, the clinical impact of these threshold values in healthy individuals has not been investigated yet. In our study, the individual with a DC <4.5 ms showed symptoms of AMS. Therefore, the DC measure may serve as an early indicator of AMS. Whereas the sensitivity and specificity of low DC levels for indicating AMS have to be analyzed in studies of larger cohorts.

Of note, there was no significant change of standard HRV parameters after altitude exposure in our study (Table 1). In addition, DC levels did not correlate with HRV parameters. These findings suggest that DC may be more sensitive than standard HRV parameters to detect a dysbalance of the autonomous nerve system at high altitude.

One of the major advantages of DC over standard HRV measures is its robustness against artifacts and noise (Bauer et al., 2006b; Eick et al., 2015). If future studies could confirm the predictive value of DC in identifying beginning AMS, the technology of DC assessment might be particularly useful for implementation in wearables or smartphones.

In parallel to DC changes, SpO₂ decreased significantly from 97.8 ± 1.0% to 92.0 ± 1.8% (p < 0.01) but increased to 94.5 ± 1.4% 24 hours thereafter. Heart rate increased slightly immediately after altitude exposure, and further increased with significance compared with baseline after 24 hours (Fig. 2). These effects are well known as physiologic responses to hypoxic environment (Bartsch and Gibbs, 2007). A further response to hypoxia is an increase of respiratory rate. In turn, Wang et al. (2015, 2016) could show that the respiratory rate influences DC levels, and that DC levels correlate with HRV parameters. In our study, we did not detect a correlation of DC levels with standard HRV parameters, neither at baseline under normoxic conditions nor after altitude exposure under hypoxic conditions. We cannot exclude an influence of respiratory rate on DC levels, since we did not assess respiratory rate in our study subjects.

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FIG. 2.

(A) The diagram shows the mean heart rate at baseline, T1 and T2. (B) The diagram shows the oxygen saturation at baseline, at T1 and T2.

Future studies are necessary to confirm our findings in a larger cohort and in additional altitude levels (>3000 m). Furthermore, future studies may investigate whether altitude-induced DC changes could predict AMS.

To the best of our knowledge, the results of this pilot study show for the first time a decrease of DC of heart rate, providing a novel insight into the dysbalance of autonomic nervous system in high altitude.