Introduction

The software module “ANS Diagnostics” is part of the custo diagnostic Holter ECG analysis. It represents a tool for analysing heart rate variability (HRV) and allows statements as to sleep quality and objective stress exposure. ANS Diagnostics allows the measurement of vagal tone and sympathetic tone based on the regulation rhythm of both systems, by using non-invasive methods. It also allows statements as to the condition of the regulatory situation of the autonomic nervous system.

As a central parameter, the sympathovagal quotient (SQ) is indicated which is calculated from the ratio between sympathetic and parasympathetic activity. It is consequently a measure for the sympathovagal balance. Standard ranges are indicated for comparability and classification, based on the assessments of several thousand patient measurements.

The ChronoCardioGram

The ChronoCardioGram is a time-variant spectral analysis of HRV and is based on a (ideally) 24h-measurement of RR intervals of the ECG. The time axis is horizontal, the frequency axis in Hertz (Hz) is vertical.

Obviously, the four colours blue, white, yellow and red reflect the intensity of the regulation rhythm in different frequency ranges. Blue means that in the corresponding frequency bands no rhythm of the autonomic nervous system can be recognized. With increasing frequency (up to 0.5 Hz) the blue colour dominates the area because ANS activity decreases above 0.3 Hz. If something goes up to 0.5 Hz it is mostly artefacts, e. g. contact errors in the signal reception or extra systoles.

Chart 1: The ChronoCardioGram

The frequency bands of the ChronoCardioGram

The individual frequency bands correspond to the following ANS activities, blue meaning inactivity, light blue and white meaning low activity and yellow and red meaning high activity (from bottom to top):

Very Low Frequency Variability (VLF)

(Frequency range: 0.003-0.04 Hz; Duration of period: 5 min to 25 sec)
The range of 0.003 to 0.04 Hz normally shows yellow to red areas during the day and in REM sleep – this reflects the rhythm of the peripheral circulation processes (opening and closing of microcirculation). The main band is at 0.017 Hz, which means 1 min. This minute rhythm is related to physical activity, thermic regulation but also to emotions and is primarily caused by the sympathetic nervous system.

Low Frequency Variability (LF)

(Frequency range: 0.04-0.15 Hz; Duration of period: 25 sec to 6 sec)
White, yellow, red areas or horizontal lines in the range of approximately 0.08 to 0.12 Hz reflect the blood pressure variability and occur with concentrated work as well as mental activity (e. g. calculating, PC work). The main band is at 0.1 Hz, which means 10 sec. The so-called “low frequency” (LF) range of these blood pressure fluctuations is mainly controlled by the sympathetic nervous system and indicates that there is stress exposure, however in the sense of controllable stress (Eustress).

High Frequency Variability (HF)

(Frequency range: 0.15-0.5 Hz; Duration of period: 6 sec to 2 sec)
Respiratory Sinus Arrhythmia, short RSA. White or yellow clouds or lines in the main band of approximately 0.25 Hz (which means 4 sec duration of period) illustrate the respiratory rhythm in the heart beat. The more distinctive it is, the stronger the modulation of heart rate through respiration. The so-called “high frequency” (HF) range is largely controlled by the parasympathetic nervous system and is a good measure for the heart-protective and anti-inflammatory vagal activity.

Further frequency bands

(Frequency range: 0.4-0.5 Hz)
In this range, biological activities can only be expected in case of rapid breathing or in infants. However, heaped occurrence of extra systoles or ECG artefacts can become visible as white, vertical lines here.

In the course of time from left to right, the image reveals further patterns which partly result from daily activities (e. g. students’ break activities or lectures), but which partly illustrate a slow endogenous rhythm, particularly during sleep. Here, the BRAC cycle has to be mentioned in particular.  

The Basic Rest and Activity Cycle (BRAC) is a 1.5 to 2-hour rhythm consisting of longer resting phases at night (Non-REM sleep, quiet sleep, stadium 2-4) and shorter phases after falling asleep, however of an activation phase (REM sleep) getting longer in the morning. A good sleep architecture provided, deep sleep phases can be detected due to activity in the HF range (breathing rhythm) and missing or low VLF and LF activity. In the REM phases increased activity in the VLF range (blood circulation rhythm) can be observed, an expression of emotional processing of the daily events. A good sleep architecture is a sign for good sleep quality.

During daytime, the BRAC can occur the other way round: 90 min of activation, then need for rest, which can be a standard for good planning of work and regeneration.

Stress/Regeneration

The diagram "Stress/Regeneration", also called sympathovagal quotient, reflects the relation between “recreation” or regeneration (activity of parasympathetic nervous system) (blue areas) and “Activation” or stress exposure (activity of sympathetic nervous system) (red areas). The numerator characterizes the sympathetic activity, the denominator the vagal activity. A ratio of 2:1 indicates that the sympathetic activity is twice as high as the vagal activity, 1:3 means that the vagal activity is 3 times higher than sympathetic activity.

Chart 2: The diagram “Stress/Regeneration”

The diagram gives a very quick overview of the distribution of activity and resting phases during the day and shows when these phases take place. The relation between these two impacts during the night can be evaluated as one measure for sleep quality.

Basic Rest and Activity Cycle (BRAC), a 1.5 to 2-hour rhythm, can be particularly well recognized during sleep (details see above). During recuperative sleep the deep (Non-REM) and REM sleep phases can be recognized as up and down of the sympathovagal quotient, a good sleep architecture provided. Good sleep recovery is given with a decrease of the quotient during the Non-REM phases in the blue area.

Daily rhythm (24h rhythm). This rhythm can be especially well recognised as up and down of heart rate and the sympathovagal quotient over 24 hours.

Studies have shown that a significant progress during daytime is a sign for intact regulation and allows a better prognosis, e. g. in oncological patients but also in patients with cardiac diseases. This context is known in hypertensive patients who as “dippers” (well pronounced daytime progress with a drop of systolic blood pressure at night) can be much better evaluated than “non-dippers” (no or low nocturnal dropping) from a prognostic point of view.

Variability/Vagal Activity

The diagram “Variability (=SDNN_RR) / Vagal tone (here = logRSA)" contains two important HRV values.  

SDNN_RR (the purple band), the standard deviation from mean heart beat is recorded every five minutes so that a curve form arises over the measurement period. Typically, peak times can be found in the REM phases of sleep, especially in the wake-up phase. There are ruptures in the deep sleep phases and in the recovery phases after physical work.

The light blue band "logRSA" is an illustration of the decadal logarithm of the Respiratory Sinus Arrhythmia and represents a measure for the activity of the parasympathetic nervous system. For this value and the heart rate there is a standard reference value according to sex and age. The "logRSA" is high in case of good coordination of heart beats and respiratory rhythm. In this example, it amounts to an average of 1.2ms over the whole period. A higher plateau especially arises in the sleep phase (activity of parasympathetic nervous system towards regeneration).

Chart 3: The diagram “Variability/Vagal activity”

Measured Value Table with Standard Ranges

The measured value table supplies data as to the most important and stable HRV parameters, such as SDNN, logRSA and sympathovagal quotient. The table differentiates between day and night phase and a summary 24h-view. In order to better classify the measurement results, standard ranges are indicated which consist of several thousand measurements, based on the comparable collectives (age and sex). The regulation ability of the autonomic nervous system depends largely on these two parameters and decreases with growing age. This is why actually no representative reference values are available for the age groups of >70 years.

In table 1 the selected parameters are listed. Those parameters were chosen intentionally which proved particularly stable and reliable for comparative considerations.

Table 1: Explanation of abbreviations in the measured value table

Evaluation considerations

For evaluating ANS diagnostics, it makes sense to consider the following aspects:

1. ChronoCardioGram – Frequency bands
   1. Can a structural difference between day and night be detected?
   2. Can a sleep architecture be detected – deep sleep (Non-REM and REM phases?), how well is it pronounced?
   3. Is the vagal tone (0.15-0.5 Hz) in the night significantly pronounced and thus recovery is provided? Is the vagal tone detectable during the day (daytime tiredness?) or before sleep (TV sleep)?
   4. Can breaks be detected during the day (according to the temporary reduction of sympathetic tone in the LF range or increase of vagal tone (-> conscious break, BRAC Cycle)?
   5. Are the 3 frequency bands HF, LF, VLF strong or reduced?
2. Stress / Regeneration  
   1. Is there a balance over 24 hours (Vagal tone in the night or in breaks), detectable also through SQ in the standard range?
   2. During sleep, the SQ should be lower than in awake state and ideally pass into the blue, vagal area several times and rhythmically (BRAC).
3. Measured value table with data from comparison collectives
   1. The average heart rate should not exceed / fall below a certain critical, age-dependent maximum and minimum within a day. The total variability SDNN should be at the top end of the age group and be higher during the day than during the night.
   2. The logRSA respectively HF as a measure for the vagus, should be high especially during night in group comparison (recovery). During the day, it is often a sign for daytime tiredness.
   3. If the LF is high in group comparison during the day and at night, a potential overstrain is given, e.g. caused by stress. At night, LF should be reduced as this is a sign for good mental regeneration (ability to relax).
4. Sympathovagal Quotient
   1. The SQ as a measure for the total regulation work of the autonomic nervous system should not exceed the standard value, in order to guarantee a reserve for exceptional charges.
   2. The SQ should be considerably higher during the day than during the night because during daytime the performance and externally oriented sympathetic part is to be active, whereas during the night the parasympathetic part of the NS is to dominate.
   3. The SQ in the measured value table should be in the central area of the percentile. At night, a low SQ is a sign for good ability to regenerate.

Hint: If the average heart rate and the sympathovagal quotient exceed their standard value ranges, the values will be highlighted in yellow. The SQ will also be highlighted in yellow if LF and HF become very small and HF is superior to LF.

Case Studies

1: Chronocardiogram & value table: Patient, female, 29 years, no known pre-existing diseases

Evaluation

During the day, strong sympathetic and parasympathetic activity in all areas. Good regulation status.

In the afternoon, vagally controlled breathing rhythm of 13-17h (sign of tiredness). Stress/Regeneration: Moderate stress exposure from 16.30h to 18.30h, at around 21h and from 6.00h to 7.30h, recovered in the morning and no hints as to tiredness. Sleep duration of 7.5 hours with short sleep-onset latency, morning type, good sleep quality, no visible sleep disorders. Strong parasympathetic activity in the non-REM phases as expression of good sleep recovery, regular sleep architecture with BRAC cycles (approx. 90min period duration).

REM phases regular and with normal latency and duration. Autonomic regulation strong and vital, good sleep recovery.

2: Chronocardiogram & value table: Patient, male, 24 years, no known pre-existing diseases

Evaluation

During the day, strong sympathetic and parasympathetic activity in all areas. Good regulation status. In the afternoon, vagally controlled breathing rhythm from 13-14.30h, 16-17h (sign of tiredness). Moderate cyclical stress exposure at 12h, 15h, 16.30h and 18h, moderate stress exposure in the morning, recovered in the morning.

Sleep duration of 6.5 hours with short sleep-onset latency, morning type, middle to good sleep quality, no visible sleep disorders. Strong parasympathetic activity in the non-REM phases as sign of good sleep recovery, slightly irregular sleep architecture with slightly prolonged BRAC cycles (more than 90 min period duration).

REM phases normal and largely regular. Autonomic regulation strong and vital.

3: Chronocardiogram & value table: Patient, male, 25 years, no known pre-existing diseases

Evaluation

Strong ANS activity during the day, especially the sympathetic part. Good regulation status. Very strong and focused sympathetic LF activity (blood pressure rhythm) indicates concentrated mental work. In the afternoon, slight vagally controlled breathing rhythm from 12.30-15h, 16-17h (sign of slight tiredness).

Stress/Regeneration: Strong stress exposure from 8h to 16h, 20-23h (17-20h recording missing). Sleep duration of 7.5 hours with prolonged sleep-onset latency (approx. 30min). Strong and regular vagal activity (HF) in the non-REM phases but at the same time high sympathetic activity (LF) during the entire sleep duration (sign of processing of daily events in sleep), otherwise no visible sleep disorders. Slightly prolonged BRAC cycles (more than 90 min period duration).

In total, also in sleep strongly ergotropic. REM phases irregular and with slightly prolonged latency and shortened duration, especially at the beginning of sleep. Autonomic regulation strong and vital.

Conclusion

The analysis of heart rate variability is based on the exact and objective measurement of the differences from heart beat to heart beat. These differences result from the ability of the autonomic nervous system to regulate very finely the impacts of its sympathetic and parasympathetic parts.

With ANS Diagnostics, these influences can be exactly measured and statements can be made as to both the condition and the regulatory ability of the sympathetic and parasympathetic parts of the autonomic nervous system.

With ANS Diagnostics, the user (physician) can make reliable statements as to sleep quality and objective stress exposure of a patient. Phenomena that have been difficult to diagnose so far can now be better identified, for example masked hypertension. The knowledge of sleep quality and the objective stress exposure is also decisive for the type and scope of a therapy.

A central parameter for a summary evaluation of the autonomic nervous system is the sympathovagal quotient (SQ). It is an objective measure for the relation of sympathetic and parasympathetic activity and thus for the sympathovagal balance.

Only through the comparison of a patient measurement with its reference values from the measured value table (which date from the measurements of a representative collective), the physician is able to perform an evaluation of the patient. Consequently, it supplies an essential basis for the interpretation of the measurement results.

Important note:
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