Clinical Significance of HRV
Methods of HRV Analysis
HRV Response to Controlled Autonomic Stimulation
Paced Breathing Test
The origin of heartbeat is located in a sino-atrial (SA) node of the heart, where a group of specialized cells continuously generates an electrical impulse spreading all over the heart muscle through specialized pathways and creating process of heart muscle contraction well synchronized between both atriums and ventricles. The SA node generates such impulses about 100 – 120 times per minute at rest. However, in a healthy individual, the resting heart rate (HR) would never be that high. This is due to continuous control of the autonomic nervous system (ANS) over the output of SA node activity. Its net regulatory effect gives real HR. In a healthy subject at rest, it ranges between 60 and 80 beats per minute.
The autonomic nervous system is a part of the nervous system that non-voluntarily controls all organs and systems of the body. As the other part of nervous system ANS has its central (nuclei located in brain stem) and peripheral components (afferent and efferent fibers and peripheral ganglia) accessing all internal organs. There are two branches of the autonomic nervous system - sympathetic and parasympathetic (vagal) nervous systems that always work as antagonists in their effect on target organs.
For most organs including heart, the sympathetic nervous system stimulates organ’s functioning. An increase in sympathetic stimulation causes an increase in HR, stroke volume, systemic vasoconstriction, etc.
In contrast, the parasympathetic nervous system inhibits functioning of those organs. An increase in parasympathetic stimulation causes a decrease in HR, stroke volume, systemic vasodilatation, etc.
A heart response time to sympathetic stimulation is relatively slow. It takes about 5 seconds to increase HR after actual onset of sympathetic stimulation and almost 30 seconds to reach its peak steady level.
The heart’s response to parasympathetic stimulation is almost instantaneous. Depending on actual phase of heart cycle, it takes just 1 or 2 heartbeats before heart slows down to its minimum proportional to the level of stimulation.
At rest, both sympathetic and parasympathetic systems are active with parasympathetic dominance. The actual balance between them is constantly changing in attempt to achieve optimum considering all internal and external stimuli.
There are various factors affecting autonomic regulation of the heart, including but not limited to respiration, thermoregulation, humoral regulation (rennin-angiotensin system), blood pressure, cardiac output, etc. One of the most important factors is blood pressure. There are special baroreceptive cells in the hear and large blood vessels that sense blood pressure level and send afferent stimulation to central structures of the ANS that control HR and blood vessel tonus primarily through sympathetic and somewhat parasympathetic systems forming continuous feedback dedicated to maintain systemic blood pressure. This mechanism is also called baroreflex, which increases HR when blood pressure decreases and vice versa. This mechanism is also targeted to maintain optimal cardiac output.
The heart rate variability analysis is a powerful tool in assessment of the autonomic function. It is an accurate, reliable, reproducible, yet simple to measure and process. The source information for HRV is a continuous beat-by-beat measurement of interbeat intervals. The electrocardiograph (ECG or EKG) is considered as the best way to measure interbeat intervals. ECG is an electrical signal measured with special conductive electrodes placed on chest around heart area or limbs. It reflects minute changes in electrical field generated by heart muscle cells originating from its SA node. ECG signal has a very specific and robust waveform simple to detect and analyze. Because of that cardiac rhythm derived from ECG is the best way to detect not only true sinus rhythm but all types of ectopic heartbeats, which must be excluded from consideration of HRV analysis.
The other approach to measuring cardiac intervals is a measurement of pulse wave. It is a less invasive and simple method of measurement based on photoplethysmograph. PPG is a signal reflecting changes in a blood flow detected when infrared light is emitted towards microcirculatory blood vessels. Depending on blood flow volume certain portion of that light is absorbed letting other part to pass or b reflected. An optical sensor detects a quantity of light passed (or reflected from) the blood flow producing a waveform identifying pulse wave. Such waveform can also be processed to derive beat-by-beat interbeat intervals. Although PPG gives the summary information reflecting both cardiac and blood vessel components of HRV, some research studies showed a significantly high correlation between interbeat interval data measured by both ECG and PPG in short-term steady-state recordings. The best selling product on HRV market Hearth Rhythm Scanner supports both devices: ECG and PPG.
One of the important issues when measuring either ECG or PPG is the absence of abnormal heartbeat used in interval detection. Only heartbeats originated in SA node can be processed to obtain HRV data. Whether there are ectopic heartbeats (PVCs or other types of extrasystolic heartbeats) or various movement artifacts on ECG (or PPG) considered as heartbeats, they must be excluded from consideration. There are various statistically-based algorithms of detection of such abnormal heartbeats that minimize chances to get contaminated HR recordings. Nevertheless, for the sake of accuracy in HRV analysis it is important to be able to visually verify all heartbeats automatically found, remove abnormal ones and include missing. The Heart Rhythm Scanner has an automatic detection of such movement artifacts and also gives the possibility to manually correct it.
Clinical Significance of HRV
It is found that lowered HRV is associated with aging, decreased autonomic activity, hormonal tonus, specific types of autonomic neuropathies (e.g. diabetic neuropathy) and increased risk of sudden cardiac death after acute MI.
Other research indicated that depression, panic disorders and anxiety have negative impact on autonomic function, typically causing depletion of parasympathetic tonus. On the other hand an increased sympathetic tonus is associated with lowered threshold of ventricular fibrillation. These two factors could explain why such autonomic imbalance caused by significant mental and emotional stress increases risk of acute MI followed by sudden cardiac death.
Aside from that, there are multiple studies indicating that HRV is quite useful as a way to quantitatively measure physiological changes caused by various interventions both pharmacological and non-pharmacological during treatment of many pathological conditions having significant manifestation of lowered HRV.
However it is important to realize that clinical implication of HRV analysis has been clearly recognized in only two medical conditions:
Predictor of risk of arrhythmic events or sudden cardiac death after acute MI.
Clinical marker of diabetic neuropathy evolution.
Nevertheless, as the number of clinical studies involving HRV in various clinical aspects and conditions grows, HRV remains one of the most promising methods of investigating general health in the future.
Methods of HRV Analysis
Short-term HRV analysis requires much shorter recordings – typically 5-min long. However such recordings are assumed to be done at steady-state physiological condition and should be properly standardized to produce comparable data. Typically, such measurements should be done in either supine or comfortably sitting relaxed position, limiting body movements, conversations, any mental activities.
According to the standards set forth by the Task Force of the European Society of Cardiology and North American Society of Pacing and Electrophysiology in 1996, there are two methods of analysis of HRV data: time- and frequency-domain analysis. In either method, the interbeat intervals should be properly calculated and any abnormal heartbeats found. Currently Heart Rhythm Scanner and Heart Rhythm Scanner Special Edition are developed supporting their standards.
Time-domain measures are the simplest parameters to be calculated. Before such calculation, all abnormal heartbeats and artifacts must be removed from consideration. The following time-domain parameters can be calculated for both long-term and short-term recordings: Mean HR, SDNN and RMS-SD. Some extra parameters can be calculated specifically for long-term recordings. The time-domain parameters are associated mostly with overall variability of HR over the time of recording, except RMS-SD, which is associated with fast (parasympathetic) variability.
A standard spectral analysis routine is applied to such modified recording and the following parameters evaluated on 5-min time interval: Total Power (TP), High Frequency (HF), Low Frequency (LF) and Very Low Frequency (VLF). When long-term data is evaluated an additional frequency band is derived – Ultra Low Frequency.
The HF power spectrum is evaluated in the range from 0.15 to 0.4 Hz. This band reflects parasympathetic (vagal) tone and fluctuations caused by spontaneous respiration known as respiratory sinus arrhythmia.
The LF power spectrum is evaluated in the range from 0.04 to 0.15 Hz. This band can reflect both sympathetic and parasympathetic tone.
The VLF power spectrum is evaluated in the range from 0.0033 to 0.04 Hz. The physiological meaning of this band is most disputable. With longer recordings, it is considered to represent sympathetic tone as well as slower humoral and thermoregulatory effects. There are some findings that in shorter recordings VLF has fair representation of various negative emotions, worries, rumination etc.
The TP is a net effect of all possible physiological mechanisms contributing in HR variability that can be detected in 5-min recordings, however sympathetic tone is considered as a primary contributor.
The LF/HF Ratio is used to indicate balance between sympathetic and parasympathetic tone. A decrease in this score might indicate either increase in parasympathetic or decrease in sympathetic tone. It must be considered together with absolute values of both LF and HF to determine what factor contributes in autonomic disbalance.
Both Heart Rhythm Scanner and Heart Rhythm Scanner Special Edition are designed to evaluate time and frequency domain analysis parameters.
HRV Response to Controlled Autonomic Stimulation
There are several techniques that allow for autonomic assessment by means of applying certain stimuli that evoke specific responses of either branch of the autonomic nervous system.
Paced Breathing Test
The reflex arc associated with breathing evokes a specific response in heart rate variability. It was first described by Genovely and Pfeifer:
Tidal volume expands the lungs, which activates stretch receptors in the lung, chest wall and heart chambers. The activated sensors stimulate the afferent nerve (vagus nerve). The central processing unit located in the brainstem (the nucleus solitarius) processes information and then decreases parasympathetic tone and/or increases sympathetic tone by sending the appropriate impulses down the efferent vagus and cervical-thoracic-sympathetic nerves, respectively. This information terminates in end-organ (the heart), which responds with an increase in heart rate. Because the reflex arc associated with the R-R variation test is reasonably well known, interpretation of test results is easier to determine than those of the reflex arcs, which are poorly described and understood (such as gastric emptying) or to reflex arcs that are more complicated.
This end-organ response is used in assessment of the autonomic function with the test method described by Wheeler and Watkins in 1973:
With this method, the subject sits quietly while his heart rate is recorded on an ECG. He is then asked to breathe deeply and regularly at a rate of six breaths per minute (5 seconds in, 5 seconds out) for one minute, while the ECG record is continued. The longest and shortest R-R intervals during each breathing cycle are measured from the ECG and converted to beats per minute.
The heart rate variability in this test may be presented in the following parameters: Expiratory/Inspiratory Index (E/I), Standard Deviation, Mean Variance of R-R, etc.
The cardiovascular response to the act of changing a posture from supine to standing was used as an indication of the autonomic function in diabetics for a long time. It is one of several tests described by
that have certain clinical value because they are simple, non-invasive, easy-to-use, reproducible and have clear difference between normal and abnormal results.
During the test, the patient rises from a supine to a standing position. Normally this causes an immediate increase in heart rate and reaches its maximum level at about 15th heartbeat after beginning to stand. It is followed by a relative bradycardia that reaches its maximum around 30th heartbeat. The phenomena can be quantified as 30:15 ratio, which is the ratio of the longest R-R interval around 30th heartbeat to the shortest interval around 15th heartbeat.
Bennet, Hosking and Hampton et al. have studied the relationship between changes in HR and blood pressure caused by standing to demonstrate its value in assessment of the autonomic effect on cardiovascular system in diabetics. They showed a complex interaction between sympathetic and parasympathetic systems and found that parasympathetic dysfunction is typically more dramatic than damage to sympathetic system. The posture test is considered as of highest value when it is performed along with other tests like paced breathing and Valsalva maneuver. The orthostatic test can be performed in Heart Rhythm Scanner Special Edition.
The Valsalva maneuver was first described by Antonio M. Valsalva in 1707. In 1860 Einbrodt showed that Valsalva maneuver demonstrated “the integrity of the vagus nerves to the heart” – an acceleration of the heart rate during expiratory effort and slowing it down after it. Later Valsalva maneuver has become so well-known that wouldn’t require its explanation. The formal Valsalva maneuver definition was described by Hamilton et al. in 1943:
In practice the maneuver can be standardized by asking the seated subject to blow into a mouthpiece attached to a manometer to a pressure of 40 mm Hg for 15 seconds, while a continuous heart rate record is made with ECG. The result can then be simply calculated by measuring with a ruler the longest R-R interval after strain (representing the maximal bradycardia) and dividing it by the shortest R-R interval during strain (representing maximal tachycardia). This gives “Valsalva Ratio”.