RU2475183C1 - Diagnostic technique for autonomic cardiac neuropathy in patients with type 2 diabetes mellitus - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly endocrinology and diabetology. There are involved examining heart rate variability (HRV) followed by spectroscopic analysis and functional testing. Those are added with determining non-linear values: deterrent fluctuation analysis (DFA) and approximated entropy (ApEn). If observing the initial amplitude decay of the HRV spectral components - VLF less than 30 points, LF less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, lack of functional response - autonomic cardiac sympathovagal neuropathy is diagnosed. If observing the normal amplitude of the HRV spectral component -VLF more than 30 points, low LF values less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, lack of functional response LF, HF - autonomic cardiac vagal neuropathy is diagnosed. If observing the initially normal amplitudes of the HRV spectral component -VLF more than 30 points, LF more than 15 points, HF more than 15 points, DFA more than 0.7, ApEn more than 180, lack of functional response LF, HF - autonomic cardiac subclinical neuropathy is diagnosed.

EFFECT: method enables early diagnosing and typing of autonomic cardiac neuropathy for the purpose of specifying a therapeutic approach.

3 tbl, 3 ex

Description

The invention relates to medicine, in particular to endocrinology and diabetology, and relates to a method for the diagnosis of autonomous cardiac neuropathy in patients with type 2 diabetes using spectral and non-linear indicators of heart rate variability.

For many years, to assess the autonomic regulation in various pathological processes, including diabetes mellitus, a method of analyzing heart rate variability has been used. Cardio intervals are usually recorded at rest or during functional tests. For a detailed analysis of the vegetative status, as a rule, statistical indicators are used.

However, normal heart rhythm is one of the most complex physiological processes observed in nature, and the expression of this complexity in simple numbers and linear equations significantly reduces the information content of assessing heart rate variability. An analysis of heart rate variability based on non-linear measures can provide important information for the physiological interpretation of variability and for assessing the risk of sudden death. This addition is promising in creating new approaches in the diagnosis of autonomic cardiac neuropathy in type 2 diabetes. Among non-linear indicators of heart rate variability, we consider deterrent fluctuation analysis and approximated entropy.

A known method for the diagnosis of autonomous cardiac neuropathy, based on conducting cardiovascular reflexes (standard tests by Ewing). To assess the activity of the parasympathetic nervous system, a deep breathing test is used. With rare breathing, a normal slowdown of the pulse occurs by at least 15 beats per minute. In the absence of the desired reduction, the sample is considered positive. A Valsalva test is carried out using a mercury sphygmomanometer. Simultaneously with the inhalation, an ECG is recorded in the instrument tube. When the ratio of the longest RR of the cardiointerval to the shortest is less than 1.2, the sample is considered positive. To assess the symptomatic function, a wedge orthostatic test is used, during which the ECG is recorded in the supine position, and then after a stationary stay - in the standing position. In this case, the increase in heart rate normally does not exceed 15 beats per minute (S.V. Kotov, A.P. Kalinin, I.G. Rudakova. Diabetic neuropathy. - M .: Medicine, 2000, p.139-141).

The disadvantages of this method are:

- poor tolerance of functional tests by elderly patients.

- insufficient diagnostic and prognostic effectiveness of the method as a result of an empirical approach to the study of heart rate variability.

Closest to the invention is a method for the diagnosis of cardiovascular autonomic neuropathy in patients with diabetes mellitus suffering from chronic heart failure. The technique includes recording in a calm state for 5 minutes with the determination of the standard deviation of the intervals between normal sinus cardio intervals (SDNN). If the SDNN value is less than 33 ms, diabetic cardiovascular neuropathy is diagnosed (L.T. Strongin et al. Patent RU 2336811, published on 10.27.2008, IPC АВВ 5/0452).

The disadvantages of this diagnostic method are:

1. Lack of functional testing.

2. Assessment of only statistical indicators.

The objective of the invention is the early diagnosis of the disease by identifying signs of disorders of the autonomic regulation of heart rhythm in patients with type 2 diabetes and improving the quality of diagnosis by identifying three varieties of cardiac neuropathy.

A method for the diagnosis of autonomous cardiac neuropathy in patients with type 2 diabetes mellitus, including a study of heart rate variability (HRV) followed by spectral analysis and functional tests, characterized in that they record slow fluctuations of the cardiac rhythm with registration of wave frequencies in the ranges of VLF 0.004-0.08 Hz, amplitude 30-150 points, LF 0.05-0.18 Hz, amplitude 15-25 points, HF 0.18-0.05 Hz, amplitude 15-35 points with Fourier analysis at 5 stages of the examination: in the initial state rest, mental stress, during the period recovered After mental stress, during hyperventilation, recovery after hyperventilation, the power of heart rate variability (HRV) in these frequency ranges is determined, non-linear indicators are additionally determined: deterministic fluctuation analysis (DFA) approximated entropy (ApEn), and with an initial decrease in the amplitude of spectral components HRV - VLF less than 30 points, LF less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, reactivity to functional tests - diagnose autonomous cardiac neuropathy sym tovagusnoy shape; with an initially normal indicator of the amplitude of the spectral component of HRV - VLF more than 30 points, low LF values less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, reactivity to functional tests LF, HF - diagnose autonomic cardiac neuropathy of the vagal form ; with the initially normal indicators of the amplitudes of the spectral components of HRV - VLF more than 30 points, LF more than 15 points, HF more than 15 points, DFA more than 0.7, ApEn more than 180, arereactivity to functional tests of the components LF, HF - diagnose autonomous subclinical cardiac neuropathy.

The novelty of the invention.

- Record slow fluctuations of the cardiac rhythm with registration of wave frequencies in the ranges of VLF 0.004-0.08 Hz, amplitude 30-150 points, LF 0.05-0.18 Hz, amplitude 15-25 points, HF 0.18-0.05 Hz, the amplitude of 15-35 points with Fourier analysis at 5 stages of the survey. Determine the power of heart rate variability (HRV) in these frequency ranges.

- Non-linear indicators are additionally determined: deterrent fluctuation analysis (DFA) and approximated entropy (ApEn). The need for the introduction of non-linear indicators is explained by a new look at the human body as an open non-linear thermodynamic system. The ongoing physiological processes obey the laws of deterministic chaos, small impulses at the input create significant fluctuations at the output.

- With an initial decrease in the amplitude of the spectral components of HRV - VLF less than 30 points, LF less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, areactivity for functional tests - diagnose autonomic cardiac neuropathy of sympathovagal form. With an initially normal indicator of the amplitude of the spectral component of HRV - VLF of more than 30 points, low LF of less than 15 points, HF of less than 15 points, DFA of more than 0.7, ApEn of less than 180, areactivity to functional tests of LF, HF - diagnose autonomic cardiac neuropathy of the vagal form . With the initially normal indicators of the amplitudes of the spectral components of HRV - VLF more than 30 points, LF more than 15 points, HF more than 15 points, DFA more than 0.7, ApEn more than 180, arereactivity to functional tests of the components LF, HF - diagnose autonomous subclinical cardiac neuropathy.

The set of essential features of the invention allows to obtain a new technical result. Using the method of heart rate variability, based on the analysis of spectral and non-linear indicators, early diagnosis of diabetic cardiac neuropathy and diagnosis of autonomic cardiac neuropathy are carried out. Isolation of the type of autonomic neuropathy is necessary to determine the tactics of treatment - the choice of antihypertensive drugs (the appointment of β-blockers in case of depression of the parasympathetic department of the autonomic nervous system), the appointment of metabolic therapy (in the case of suppression of both links), the identification of subclinical variants of autonomic cardiac neuropathy to highlight the risk the development of this complication. Also, the type of autonomic cardiac neuropathy is important in assessing the prognosis of sudden cardiac death.

In recent decades, numerous works have appeared devoted to the study of the clinical and prognostic significance of heart rate variability in diabetes mellitus. The interest in the problem of autonomous cardiac neuropathy is explained by the fact that it is regarded as one of the unfavorable prognostic factors affecting the frequency of fatal cases in patients.

Recent studies in the field of nonlinear dynamics allow us to take a fresh look at various indicators of heart rate variability. A look at the human body as an open nonlinear thermodynamic system does not justify, but dictates the need to study nonlinear indicators (DFA, ApEn).

Detrental fluctuation analysis (DFA) is one of the methods for fractal analysis of heart rate variability, analysis of signs of self-similarity in time series. (Time series of a limited volume can be analyzed for self-similarity by integration, if there is a certain stationarity of the processes) In this case, the correlation functions should be invariant to time intervals of various durations. If this does not happen, then integration enhances the unsteadiness of the original data. To overcome this complication, a modified analysis is used by calculating the rms values. Detrential fluctuation analysis cannot be replaced by any statistical and spectral indicators.

Along with other characteristics of HRV analysis, DFA proved to be informative in assessing cardiovascular variability in adults, patients with heart disease, and dilated cardiomyopathy. In the Framingham study, based on an analysis of a two-hour ECG recording, it was found that DFA carries additional prognostic information compared to traditional frequency characteristics. In a retrospective comparison of HRV criteria, with 24-hour ECG monitoring in patients after myocardial infarction, DFA was the most informative predictor of heart rhythm disturbances and apnea.

To study the features of heart rate variability, the approximated entropy indicator is also used. The physical meaning of entropy is reflected in the second law of thermodynamics. Entropy is a measure of irreversible energy dissipation and is a function of the state of a thermodynamic system. The clinical significance of the measure of disorder is great, because loss of complexity is a sign of a disease. If the system reaches its equilibrium state (homeostasis), then the entropy becomes maximum. Estimation of ApEn has been studied in detail in the cardiodynamic process. ApEn decreases in newborns at the risk of sudden death. There was also a decrease in ApEn in adult patients in the postoperative period at risk of myocardial ventricular dysfunction and in healthy individuals after the administration of endotoxin, which reduces the heart rate.

The method is as follows.

The study of heart rate variability was carried out using a 12-channel electrocardiograph Neurosoft - Polyspectrum 8E.

Assessment of cardiac rhythm variability was carried out using functional samples of low intensity according to the method developed in 1994 by Professor Fleishman A.N. The sequence of stages of the study is presented below:

Stage 1. Registration of the initial state (background).

Stage 2. The first functional test - the account "in the mind" in the form of a subtraction from 500 to 7 (mental load).

Stage 3. The recovery phase after the first functional test.

Stage 4. The second functional test is hyperventilation.

Step 5. The recovery phase after the second functional test.

The samples used in the method stimulate the sympathetic department (sample 500-7) and the parasympathetic department (sample with deep breathing). These samples correspond to the usual daily forms of human activity, do not cause additional emotional disturbances (A.N. Fleishman. Slow hemodynamic fluctuations. Novosibirsk, Nauka, 1999, pp. 38-55).

At each of the 5 stages, short recordings were made of 256 intersystolic intervals. As additional information, data on blood pressure were introduced at each stage of the study. The study took place in the morning (from 9 to 12 hours), at rest. The total amount of analyzed information was 1280 cardio intervals at each examination. During the visual control of the recorded signal, artifacts of physiological or other origin were eliminated. The analysis of the primary data included a visual analysis of the cardiotachogram, an estimation of time indicators, frequency (VLF, LF and HF), energy, spectral, nonlinear parameters.

Among nonlinear HRV indices, we used deterrent fluctuation analysis and approximated entropy.

Three main components were distinguished in the HRV spectrum: VLF, LF, and HF.

VLF - recorded in the range of 0.004-0.08 Hz, determine the functioning of the sympathetic link of the autonomic nervous system, the amplitude of the VLF from 30-150 points.

LF - low-frequency vibrations - reflect various sides of the baroreceptor function, which includes both sympathetic and parasympathetic mechanisms. The frequency range is from 0.05 to 0.18 Hz, the amplitude of LF is 15-25 points.

HF - high-frequency oscillations - are associated with the parasympathetic nervous system and are limited by the frequency range of 0.18 to 0.5 Hz, the amplitude of HF is 15-35 points.

Of the non-linear indicators, approximated entropy (norm 180–210) and deterrent fluctuation analysis (from 0–0.5 parasympathetic predominance, from 0.6–0.7 vegetative equilibrium, more than 0.7 sympathicotonia) were estimated.

With an initial decrease in the amplitude of the spectral components of HRV - VLF less than 30 points, LF less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, ares to functional tests - they diagnose autonomous cardiac neuropathy of sympathovagal form. With an initially normal indicator of the amplitude of the spectral component of HRV - VLF of more than 30 points, low LF of less than 15 points, HF of less than 15 points, DFA of more than 0.7, ApEn of less than 180, areactivity to functional tests of LF, HF - diagnose autonomic cardiac neuropathy of the vagal form . With the initially normal indicators of the amplitudes of the spectral components of HRV - VLF more than 30 points, LF more than 15 points, HF more than 15 points, DFA more than 0.7, ApEn more than 180, arereactivity to functional tests of the components LF, HF - diagnose autonomous subclinical cardiac neuropathy.

We examined 100 patients with type 2 diabetes. Three types of autonomic cardiac neuropathy were determined depending on the amplitude (power) of spectral and nonlinear indicators, the response to low-intensity samples. Vagal variant, sympathovagal and subclinical. The boundaries are determined experimentally by statistical processing and analysis of spectral and non-linear indicators in the examined.

A general description of each type of autonomic neuropathy is presented in Summary Table 1.

Table 1 Clinical options for autonomic cardiac neuropathy HRV indicator Sympathovagus variant Vagus version Subclinical option VLF (points) * 1.13 ± 0.2 1.94 ± 0.2 2.01 ± 0.2 LF (points) 0.46 ± 0.10 0.78 ± 0.16 1.17 ± 0.2 HF (points) * 0.28 ± 0.08 0.72 ± 0.10 1.38 ± 0.19 reactivity no reaction Saved at "500-7" Saved at "500-7" DFA 0.95 ± 0.1 0.96 ± 0.01 0.83 ± 0.09 ApEn ** 156.1 ± 29.7 204.8 ± 20.8 217.8 ± 28.7 * p <0.001, ** p <0.001 between the sympathovagal and subclinical variants,

Example 1

Patient N., 37 years old. The diagnosis is type 2 diabetes, first identified. Complications - sensory polyneuropathy of the upper and lower extremities.

HRV — initially low variability in all parts of the HRV spectrum — VLF — 2.91 points, LF — 2.58 points, and HF — 0.26 points. Low values of approximated entropy (133-129), detrental fluctuation analysis - 0.96. During functional testing, the reaction of the spectrum components (VLF and HF) is not (Table 2).

This example illustrates the sympathovagal variant of autonomous cardiac neuropathy, the main characteristics of which are the depression of all components of the spectrum of heart rate variability, the reactivity of VLF, LF, HF to low-intensity samples: “500-7”, deep breathing, the HF amplitude is initially 0.26, at the moment deep breathing 0.58 points, low approximate entropy of 133.5 and DFA of more than 0.7 closer to 1, which indicates the relative predominance of sympathetic influences in the conditions of a total decrease in the amplitude of all composites Comrade HRV spectrum. When such a variant of cardiac neuropathy appears, it is necessary to carry out treatment with metabolic agents, and as a hypotensive therapy, it is advisable to prescribe cardioselective β-blockers. Low efficacy of antihypertensive therapy is expected due to the loss of autonomic effects on the cardiovascular system.

table 2 HRV indicator The amplitude of the oscillations of the HRV spectrum at the stages of the study one 2 (500-7) 3 4 (deep breathing) 5 VLF (points) 2.91 12.7 3.28 9.52 3.99 LF (points) 2,58 2.54 1.37 1.95 1.77 HF (points) 0.20 0.34 0.25 0.58 0.32 Aren 133.05 131.41 134.54 127.75 129.38 DFA 0.96 0.92 1.06 0.83 0.95

Example 2

Patient G. 52 years old.

The diagnosis is type 2 diabetes mellitus, severe, compensation.

Complications - diabetic sensorimotor polyneuropathy 2-3 degrees; diabetic macroangiopathy, stenosis of the tibial arteries. Ischemia of the lower extremities 2 degrees.

From the debut of the diagnosis of the disease - combined hypoglycemic therapy - Diabeton MB 2 tablets per day + extended-acting insulin (protafan 10 units 2 times a day). After 9 months from the onset of the disease, the patient was completely transferred to insulin therapy according to the basic bolus scheme, due to the failure of sugar-lowering therapy and prolonged decompensation of carbohydrate metabolism. At the time of the examination, blood sugar is 7.6-5.6 mmol / L. Cholesterol - 5.5 mmol / L.

When examining HRV, the initial normal VLF level was 280.01 points, the power of the right half of the HRV spectrum was reduced - LF and HF 6.63 points, 6.96 points, respectively. The reaction of near-minute rhythms to a 500-7 sample according to the type of stress instability VLF was initially 280.01 points; during stress loading, the amplitude decreases to 59.19 points. The right half of the spectrum of LF and HF does not respond to a test with in-depth breathing, initially the amplitude of HF is 6.96 points, with in-depth breathing 4.73 points. Initially, the level of approximated entropy is normal - 203.6, DFA more than 1 (Table 3).

Table 3 HRV indicator The amplitude of the oscillations of the HRV spectrum at the stages of the study one 2 (500-7) 3 4 (deep breathing) 5 VLF (points) 280.01 59.19 15.36 86.34 40.09 LF (points) 6.63 5.72 7.60 3.90 5.63 HF (points) 6.96 1.06 3.79 4.73 3.44 Aren 203.6 156.6 163.62 176.62 204.79 DFA 1,2 1.39 0.96 1.21 1.29

This example illustrates the vagal version of autonomic cardiac neuropathy, the main characteristics of which is depression of HF, with a normal amplitude of VLF, with a normal approximated entropy and DFA of more than 0.7. With this variant of autonomic cardiac neuropathy, antihypertensive therapy requires the appointment of β-blockers to achieve the target values of blood pressure.

Example 3

Patient R. 37 years.

The diagnosis is type 2 diabetes mellitus, compensation.

Complications - diabetic nephropathy in the stage of proteinuria, diabetic polyneuropathy of the lower extremities.

Blood sugar 4.7-7.8 mmol / L. Compensation of carbohydrate metabolism is achieved by taking tablets of sugar-lowering drugs. Blood pressure does not increase.

Cholesterol 4.8 mmol / L.

HRV is the initial average level of variability with a normal vegetative profile. VLF - 89.2 points, LF - 10.46 points, HF - 25.67 points. The reaction of near-minute rhythms to the VLF stress test was retained for an initial 89.2 points to the stress test, an increase in power with an increase in amplitude to 102.2 points. Low reactivity of the right half of the spectrum for a deep breathing test, which is not normal in healthy people. Noteworthy for the vegetative balance is a DFA of more than 0.7, which indicates subclinical dysregulation of heart rate variability. Satisfactory indicators of approximated entropy 207.23 (Table 4).

Table 4 HRV indicator The amplitude of the oscillations of the HRV spectrum at the stages of the study one 2 (500-7) 3 4 (deep breathing) 5 VLF (points) 89.2 102.24 60.96 54.37 67.25 LF (points) 10.46 8.43 8.71 32.62 12.77 HF (points) 25.67 12.67 13.79 15.41 10.62 Aren 207.23 191.99 210.94 215.05 202.04 DFA 0.71 0.75 0.77 0.61 0.83

This example demonstrates a subclinical version of autonomic cardiac neuropathy, the main characteristics are the initially normal amplitude of all components of the heart rate variability spectrum VLF more than 30 points, LF more than 15 points, HF more than 15 points and normal approximated entropy indicators more than 180, however, the DFA value is more than 0. 7, which is a predictor of the development of autonomic cardiac neuropathy, and requires monitoring of HRV. Metabolic therapy of α-lipoic acid and B vitamins has been prescribed.

Thus, the proposed method is convenient to use and highly informative, the sensitivity of the technique is quite high and surpasses similar methods. The claimed invention will allow the diagnosis of autonomous cardiac neuropathy in diabetes mellitus type 2.

The identification of the type of autonomic neuropathy allows one to determine the tactics of treatment - the choice of antihypertensive drugs (administration of β-blockers in case of depression of the parasympathetic department of the autonomic nervous system), the appointment of metabolic therapy (in the case of suppression of both links), identification of subclinical variants of autonomous cardiac neuropathy to highlight the risk group for development this complication.

Claims (1)

A method for the diagnosis of autonomous cardiac neuropathy in patients with type 2 diabetes mellitus, including a study of heart rate variability (HRV) followed by spectral analysis and functional tests, characterized in that they record slow fluctuations of the cardiac rhythm with registration of wave frequencies in the ranges of VLF 0.004-0.08 Hz, amplitude 30-150 points, LF 0.05-0.18 Hz, amplitude 15-25 points, HF 0.18-0.05 Hz, amplitude 15-35 points with Fourier analysis at 5 stages of the examination: in the initial state rest, mental stress, during the period recovered After mental stress, during hyperventilation, recovery after hyperventilation, the power of heart rate variability (HRV) in these frequency ranges is determined, non-linear indicators are additionally determined: deterrent fluctuation analysis (DFA), approximated entropy (ApEn), and with an initial decrease in the spectral amplitude HRV components - VLF less than 30 points, LF less than 15 points, HF less than 15 points, DFA more than 0.7, ApEn less than 180, reactivity to functional tests - diagnose autonomous cardiac neuropathy sym atovagus form; with an initially normal indicator of the amplitude of the spectral component of the HRV - VLF of more than 30 points, low LF of less than 15 points, HF of less than 15 points, DFA of more than 0.7, ApEn of less than 180, reactivity to functional tests of LF, HF - diagnose autonomous cardiac neuropathy of the vagal form ; with the initially normal indicators of the amplitudes of the spectral components of HRV - VLF more than 30 points, LF more than 15 points, HF more than 15 points, DFA more than 0.7, ApEn more than 180, arereactivity to functional tests of the components LF, HF - diagnose autonomous subclinical cardiac neuropathy.