WO2012022680A1

WO2012022680A1 - Determination of changes in an at least three-dimensionally identifiable signal that occurs periodically in a living being

Info

Publication number: WO2012022680A1
Application number: PCT/EP2011/063898
Authority: WO
Inventors: Axel Bauer; Konstantinos Rizas; Georg Schmidt
Original assignee: Axel Bauer; Konstantinos Rizas; Georg Schmidt
Priority date: 2010-08-18
Filing date: 2011-08-12
Publication date: 2012-02-23
Also published as: DE102010035308A1

Abstract

The present invention relates to a method for determining a change in an at least three-dimensionally identifiable signal that occurs periodically over time in a living being in relation to a reference living being. It further relates to a device for carrying out this method, a computer program designed to carry out this method, and a computer-readable data carrier.

Description

Determination of changes in a living being periodically occurring, at least three-dimensionally identifiable signal

The present invention relates to a method for determining a change in a living organism over time periodically occurring, at least three-dimensionally identifiable signal to a corresponding signal in a reference organism, a device for performing this method, a computer program, designed to perform this method , as well as a computer readable medium.

The determination of a change in a living organism over time periodically occurring, at least three-dimensionally identifiable signal to a reference species is in many areas of technology and in particular medicine of relevance. Three-dimensional signals occurring periodically over time can be found in biological systems. An example of this is the accumulated electrical activity of the brain, which is measured in the context of so-called electroencephalography (EEG). The potential differences generated by the heart are also such three-dimensional signals that occur periodically over time. These can be measured by means of vector electrocardiography or vector cardiography (VKG), with which the temporal course of the potential differences as they project on the body surface is spatially recorded. Changes in the potential differences over time that are generated by the heart compared with reference values determined in healthy organisms may allow conclusions to be drawn regarding the development of heart disease or even the presence of heart disease.

Thus, sudden cardiac death is one of the most frequent causes of death in the Western world. The identification of endangered high-risk patients is a major clinical problem and currently succeeds only inadequately. There is strong experimental and clinical evidence that abnormalities in the repolarization of the heart are associated with sudden cardiac death.

The reliable diagnosis of repolarization of the heart is therefore of great medical importance, since affected patients with the provision or implantation of a suitable medical device, for example. A defibrillator, targeted help and the onset of sudden cardiac death could be prevented in many cases.

Currently, such cardiac repolarization disorders are diagnosed by methods that aim to identify a so-called "T-wave alternan". T-wave alternans describes a physiological phenomenon that is identifiable in individuals in the electrocardiogram. T-wave alternans presents as a beat-to-beat variation of T-wave amplitude, also referred to as ABAB behavior. In order to induce a T-wave alternans, must the person to be examined is usually physically burdened, for example by physical activity on an ergometer. Only from high heart rates, this phenomenon may be observed. Due to the associated health risks, however, the burdening of potentially ill patients is hardly justified and requires a great deal of effort. In addition, in about one third of all patients, the test for T-wave alternans gives no result. In addition, studies have recently been published in which the identification of T-wave alternans has not been conclusive. An alternative is to search for a sporadically occurring T-wave alternans in a standard long-term ECG prepared under everyday conditions. The significance of this method, however, has not been adequately investigated.

Against this background, the invention has for its object to provide an improved method for detecting a change in a living organism over time periodically occurring, at least three-dimensionally identifiable signal against a corresponding signal in a reference organisms, in which in the prior art known disadvantages are avoided.

This object is achieved by a method comprising the following steps:

1. providing a record containing a plurality of temporally successive signals that can be identified at least three-dimensionally,

2. determination of a weighted main vector for each at least three-dimensionally identifiable signal of the data set,

3. Determination of the changes dT (t) _{P of} the spatial position of the weighted main vector of each at least three-dimensionally identifiable ren signal relative to the spatial position of the weighted main vector of a temporal subsequent at least three-dimensional identifiable signal.

4. Comparison of dT (t) _P with a reference function dT (t) _R , determined in accordance with the reference species

5. Correlation of dT (t) _P * dT (t) _R with the presence of the change.

The object of the invention is completely solved by such a method.

[0010] According to the invention, an at least three-dimensionally identifiable or locatable signal is understood to mean such a signal, preferably biological phenomena or processes, which can be assigned a defined position in three-dimensional space. However, this spatially identifiable signal may also be identifiable with respect to another 4th, 5th, 6th or nth dimension. Thus, the spatially identifiable signal can, for example, change over time and consequently be identifiable at least four-dimensionally. The spatially identifiable signal can be assigned further physical variables or dimensions, such as, for example, the temperature.

The provided in step 1 record contains all the information with which each signal spatially and preferably temporally located or identified. The data record can have a multiplicity of the at least three-dimensionally identifiable signal in a consecutive time sequence. The data may, for example, be Cartesian coordinates or else polar coordinates, by means of which the signal in space can be identified as a function of time. According to the invention, a so-called weighted main vector is determined in step 2 for each at least three-dimensional identifiable signal, which may also be referred to as an amplitude-weighted mean main vector. This preferably results from the polar coordinates of the signal for each time point, ie the azimuth and elevation angles, which are weighted with the amplitude or the radius of the signal.

It is understood that alternatively, instead of the weighted main vector, such a main vector can be determined, which characterizes the three-dimensionally identifiable signal. For example, the direction vector may be defined by the direction of the signal at the time of the maximum amplitude.

In the subsequent step 3, the changes in the spatial position of the weighted main vector of a three-dimensionally identifiable signal to the spatial position of the weighted main vector of a temporally subsequent three-dimensionally identifiable signal are determined, whereby a time signal dT (t) _{P is} obtained, in which it preferably by an angle. "P" stands for "patient". This time signal is the decisive parameter which allows conclusions to be drawn regarding the presence of a change, for example a repolarization disorder of the heart.

Alternatively, the change of the spatial location of the weighted main vector of the three-dimensionally identifiable signal relative to the spatial position of the average weighted main vector over any period of time, for example. 2, 3, 4, 5, 10, 15, 20 or 30 minutes, are determined to obtain the time signal dT (t) _P.

In the next step 4, therefore, according to the invention, a comparison of dT (t) _P with a reference function dT (t) _R determined in accordance with the reference species takes place. "R" stands for "reference organisms". The reference creature is such a living being, for example, a human, the healthy, ie no Change, for example, has no repolarization disorder of the heart, or is long-term surviving and against which, if necessary, a temporal change of the patient at least three-dimensional identifiable signal is to be determined. The reference animal has not died from the determination of dT (t) _R for a longer period of preferably at least 5 years. "Determined accordingly" means according to the invention that the method for determining dT (t) _R is the one with which dT (t) _{P is} determined.

In the subsequent step 5, the presence of a change is then diagnosed when dT (t) _{P is} not equal to dT (t) _R.

The inventors have recognized that the temporal changes of the spatial position of the weighted main vectors from a signal to the time lag, i. the time signals dT (t) between different groups of animals, for example healthy and those with repolarization disorders, surprisingly differ significantly from one another and therefore have diagnostic potential.

It is preferred according to the invention, if in step 4, a quantification of dT (t) _P to obtain an indicator value and a corresponding quantification of dT (t) _R to obtain a corresponding reference value and a comparison of indicator value and reference value, and in step 5, a correlation of indicator value reference value with the presence of the change takes place.

This measure has the advantage that the change or repolarization disturbances of the heart can be determined even more simply since no time signal has to be compared with another time signal but only a quantified indicator value with a quantified reference value. According to the invention, "corresponding quantification" means that the methodology for quantifying dT (t) _R is that with which dT (t) _{P is} quantified. The inventors have recognized that can be found in the time signal dT (t) periodicities or oscillations, for example, have a frequency of ~ 0.03Hz and are not detectable on the analysis of T-wave alternans. The time signal dT (t) can therefore be analyzed by various time domain and frequency domain methods, such as spectral analysis, wavelet analysis or phase-rectified signal averaging (PRSA) analysis.

According to the invention, it is further preferred if the determination of the change with time of a signal, which occurs periodically in a living organism over the time, of at least three-dimensionally identifiable signals relative to a corresponding signal in a reference species is the diagnosis of a repolarization disorder of the heart in a living being.

This measure has the advantage that a new method is provided, with which in a reliable manner repolarization disorders of the heart can be diagnosed. In comparison with the methods currently used in the prior art, a physical load on the living being or patient to be examined is not required, as a result of which the method according to the invention can also be used in persons who are already ill. For example, the inventors were able to show that by means of the new method or temporal function dT (t) _P and the corresponding quantified value resulting from this function, the relative risk of a patient after a myocardial infarction in the subsequent period to die, clearly is more predictable than by the conventional risk factors. In other words, the method according to the invention provides a significantly higher prognostic value than the methods currently used, and therefore allows a much more reliable therapeutic decision, for example, whether prophylactic measures such as the implantation of a defibrillator appear reasonable. The inventors were able to check this in a retrospective clinical examination of 908 infarct patients who were observed over five years after the onset of infarction. With the method according to the invention not only repolarization disorders of the heart can be diagnosed as such. It is also possible to assign the examined living beings or patients to risk groups. Thus, for example, an assignment to so-called high-risk patients can take place if the indicator value reference value applies.

According to the invention, it is preferable if the at least three-dimensional identifiable signal is the development of tension in the heart during the ventricular repolarization (T-loop).

This measure according to the invention has the advantage that a signal is analyzed over time, which, according to findings of the inventors, appears to be causally related to sudden cardiac death. In this case, the spatial course of the ventricular repolarization is also referred to as a T-loop or T-vector loop due to its representation in the vectorcardiogram and represents the three-dimensional counterpart to the T-wave in the two-dimensional ECG.

In this development of the method according to the invention, the at least three-dimensional identifiable signal corresponds to at least one part, ie a temporal section of the T-loop, for example at least the first / last temporal 1/8, at least the first / last temporal 1/4, at least the first / last temporal 1/3, at least the first / last temporal Hälte, preferably the temporally whole T-loop. Alternatively, the at least three-dimensional identifiable signal corresponds to the temporal portion from the beginning (T _start ) to the top of the T-loop or T-wave (T _peak ) or from the top (T _peak ) to the end of the T-loop or T-wave (T _end ).

In this case, it is preferred according to the invention if the data set provided in step 1 comprises measurement data from vector cardiography. This measure has the advantage that a proven in clinical routine, easy to perform and reliable measurement method is used, which provides all the data required for the implementation of the method according to the invention. By means of vector cardiography, the temporal course of the potential differences generated by the heart, as they project on the body surface, can be measured and represented, for example, by means of a vectorcardiogram (VCG). In contrast to the classical two-dimensional electrocardiogram (ECG), which shows the temporal voltage curve of empirically determined derivatives as a scalar voltage-time curve, the vector cardiogram and the vectorcardiogram additionally give the spatial progression of the voltage changes at the time of atrial and ventricular depolarization as well as ventricular repolarization vectorial, ie in the form of so-called vector loops, again. Vector cardiography therefore requires the use of certain delivery systems that compensate for the stress distortions of the organs located between the heart and body surface. In clinical context, orthogonal Frank leads or conventional 12-lead ECG leads are mostly used.

In the vectorcardiogram, the P and R loops represent the spatial progression of the voltage vectors of the atrial (P-loop) and ventricular (R-loop) depolarizations, respectively. The T-loop represents the development of tension during ventricular repolarization. The vector points with its arrowhead at any time from the electrical zero point of the heart in a certain direction in space. The magnitude of the vector or sum potential, the magnitude, is represented by the length of the arrow. Due to the angles that the sum vector forms with the frontal plane, the so-called elevation angle, and which forms the sum vector with the horizontal plane, the so-called azimuth angle, its spatial orientation is clearly defined.

It is inventively preferred if step 3 of the method according to the invention by mathematical transformation of the Cartesian coordinates x, y, z of at least three-dimensionally identifiable signal or the T-loop in the polar coordinates azimuth angle, elevation angle and radius or Amplitude takes place. Further, it is preferable that, in step 3, dT (t) _{P is determined} as an angle measure.

By these measures, the at least three-dimensional identifiable signal or the T-loop is optimally imaged at any time and detects the maximum excitation. These measures have the advantage that the subsequent determination of the weighted main vector is made possible in a simplified manner.

It is preferred that in step 3, the temporal change dT (t) _{P of} the spatial position of the weighted main vector of each at least three-dimensionally identifiable signal or each T-loop relative to the spatial position of the weighted main vector of the temporally next following at least three-dimensionally identifiable signal or the temporally next following T-loop is determined.

Although the inventors have realized that relatively good results are achieved even if, for example, only every third signal or every third T-loop is analyzed, the analysis of each individual signal or loop will be particularly good and reliable Results achieved.

In this case, it is preferred according to the invention if, in step 4, dT (t) _{P is} transformed into a PRSA _P signal by means of "phase-rectified signal averaging" (PRSA) and a comparison with a correspondingly transformed into a PRSA _R signal dT (t) _R occurs.

The PRSA analysis is described, for example, in Bauer et al. (2006), phase rectified signal averaging detects quasi-periodicities in non-stationary data; Physica. A. 364: 423-434, or in Bauer et al. (2006), Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study; Lancet 367 (9523): 1674-81. The content of the above publications is incorporated by reference in the disclosure of the present invention. The PRSA analysis is especially useful for non-stationary, noisy signals, ie signals whose characteristics can change over time. This is the case with most biological signals, for example also with the repolarization signal in the heart or the T-loop. The PRSA analysis transforms an arbitrarily long time signal into a new, much shorter time signal, the so-called PRSA signal. In this all periodic or oscillatory components of the original signal are included. However, non-periodicities and noise are largely eliminated. "Transformed accordingly" means according to the invention that the methodology for transforming the PRSA _R signal is that used to transform the PRSAp signal.

In this case, it is preferred if in the method according to the invention the indicator value is a measure of the amplitude in the center of the PRSA _P signal and the reference value is a measure of the amplitude in the center of the PRSA _R signal.

This measure has the advantage that a particularly suitable indicator value or reference value is determined. These can be determined, for example, by means of the Haar wavelet transformation. The Haar wavelet transform quantifies the amplitude in the center of the PRSA signals, as it were. There, due to the method, all oscillations are in phase, and their amplitudes add up.

In this case, it is preferred according to the invention if, in step 6, the following applies: correlation of indicator value> reference value with the presence of the change or the diagnosis of a repolarization disorder of the heart.

This measure has the advantage that the fact recognized by the inventors that patients who died in the follow-up period have significantly greater indicator values than non-deceased patients is used diagnostically. Thus, it is also possible by means of the method according to the invention to diagnose not only a repolarization disorder of the heart, but also to assign the examined patients to a high-risk group if indicator value> reference value applies or to assign it to a low-risk group if indicator value <reference value applies.

In this case, it is preferred if in step 1 of the method according to the invention the provided data record at least 60, preferably at least 120, 180, 240, 300, 600, 900, 1200 and most preferably at least 2000 at least three-dimensional identifiable signals or T-loops represents. Alternatively, it is preferred if vector cardiography was performed over a period of at least one minute, preferably at least over 2, 3, 4, 5, 10, 15, 20, and most preferably at least 30 minutes.

This measure has the advantage that a sufficient number of signals or T-loops are analyzed so as to obtain a particularly meaningful result.

Another object of the present invention relates to an apparatus for performing the method according to the invention, which further preferably comprises a data carrier containing the data set from step 1 of the method according to the invention, as well as an evaluation device which is used to determine the weighted main vector for each T-loop, for determining the time function dT (t) _P , for quantifying the time function dT (t) _P and obtaining an indicator value, for correlating the indicator value with a reference value, and for setting the diagnosis.

The features and advantages mentioned in connection with the method according to the invention apply correspondingly to the device according to the invention. The data set is obtained via a discharge system, preferably an orthogonal or bipolar derivative, for example a Frank derivative.

This measure has the advantage that in this way the potential differences generated by the heart in the course of time can be detected spatially.

According to the invention, the evaluation device preferably has a processor.

The evaluation device can consequently be a computer.

Another object of the present invention relates to a computer program which is designed to carry out the method according to the invention, and a computer-readable data carrier having the computer program according to the invention.

It is understood that the features mentioned above and those yet to be explained not only in the particular combination, but also in other combinations or alone, without departing from the scope of the present invention.

The present invention will now be explained in more detail by means of embodiments in which reference is made to the accompanying figures. These show the following:

Fig. 1 illustrates the spatial representation of a three-dimensional

Process at a specific point in time as a point in the Cartesian coordinate system. This point is defined by an x, y and z value. In the polar coordinate system this point becomes defined by the two angles azimuth and elevation as well as an amplitude (radius);

2 shows the time profile of a T-loop, represented in the Cartesian coordinate system (partial images A, B and C) or in the polar coordinate system (partial images D, E and F), on the x-axis is the time in milliseconds ( ms), the voltage in millivolts (mV) is plotted on the y-axis;

3 illustrates the determination of the weighted average azimuth (WAA) and the weighted average elevation (WEE) from the polar coordinates for each measured value of a T-loop (A) and shows by way of example the mathematical determination on the basis of 6 measured values (B);

FIG. 4 shows by way of example the weighted main vector of a T-loop in FIG

Projection onto a sphere;

Fig. 5 illustrates the detection of the time signal dT (t) by calculating the angle between two adjacent T-waves;

FIG. 6 illustrates the temporal variation of dT (t) determined for FIG. 3

T-loops or T-waves projected onto a sphere;

Fig. 7 shows typical dT (t) time signals one within five years after

Record of signal surviving (lower open line) and deceased patients (upper filled line) over 200 heartbeats; 8 shows the quantification of the time signal dT (t) of a deceased patient by means of frequency analysis (partial image A) and by means of PRSA analysis (partial image B);

9 shows the result of a PRSA analysis of a time signal dT (t) of a surviving (left) and a deceased (right) patient, TWR = "T-Wave Rhythmicity";

Fig. 10 illustrates the different TWR values for survivors

(left) and deceased patients (right);

11 shows the result of a log-rank test statistic for determining the optimal separation value between surviving and deceased patients.

Figure 12 shows the mortality rates in patients with normal TWR as well as with abnormal TWR.

embodiments

1. Receipt of the record

Of the patients to be examined, a vector electrocardiogram or vectorcardiogram (VCG) is recorded over a period of several minutes, preferably 20 to 30 minutes, in the resting state. This is done by derivations that allow a three-dimensional reconstruction of the repolarization processes, as is possible, for example, by an ordinary 12-channel recording or an orthogonal Frank derivative and a McPhee derivative. Implementation of the method according to the invention Spatial representation of repolarization events

The T-loop as a three-dimensional process can be represented at any time in the Cartesian coordinate system, i. At any given time, the process is defined by an x, y, and z value. The spatial direction of the repolarization can alternatively be described for each time point in the polar coordinate system by means of two angles, namely the azimuth and elevation angle; see. Fig. 1. The conversion of data of the Cartesian coordinate system into data of the polar coordinate system is described in the prior art.

Corresponding algorithms for the conversion are carried out automatically when creating vectorcardiograms.

Each repolarization event consists of a certain number of measurements according to the drawing frequency. With a drawing frequency of 1000 Hz and a duration of the T-loop of 300 ms, approximately 300 measured values are obtained. Consequently, for each time point of the T-loop one obtains a value for the polar coordinates azimuth, elevation and amplitude.

2, the course of the T-loop in the x-, y- and z-direction of the Cartesian coordinate system over time is shown in the partial images A, B and C. Subpictures D and E show the course of the azimuth and elevation angles for each time point of the T-loop. It can be seen that the standard derivative in the x-direction (FIG. 2A) already maps the T-loop relatively well, ie at most points in time the direction of the excitation is directly in or out of the derivative. Nevertheless, a virtual electrode is conceivable that could reposition itself at any time of the T-wave to capture the maximum excitation. This virtual derivative is in of Fig. 2F and is similar in function to a human eye, which is at any time new sharp.

Determine the weighted main vector for each T-loop

For each repolarization event of the T-loop, based on the data obtained, a so-called weighted main vector is calculated, which should characterize the repolarization event. The weighted main vector consists of two values, a weighted average azimuth and a weighted average elevation.

The calculation of the weighted average azimuth and mean elevation is done in the following way:

(Amp _t * azimuth _t )

Weighted average azimuth (WAA)

Y _J Amp _t

^ (Amp _t * elevation _t )

Weighted average elevation (WAE)

^ Amp _t

The calculation is illustrated in FIG. 3.

The weighted average azimuth and the weighted average elevation determine the main direction of repolarization in three-dimensional space, corresponding to an arrow in a sphere; see. Fig. 4. It is understood that the main vector characterizing the repolarization can be calculated in other ways.

Determination of dT (t)

In the next step, the temporal change dT (t) of the spatial position of the weighted main vector of each T-loop with respect to the spatial position of the weighted main vector of a temporally following T-loop is determined as an angle measure. This is illustrated in FIG. 5A.

The calculation of dT (t) is shown below:

dT (t) _x sin (WAE ₁ ) * cos (WAA ₁ ) * sin (^ ₂ ) * cos (WAA ₂ )

dT (t) _y cos (WAE ₁ ) * cos (WAE ₂ )

dT (t) ₂ sin (WAE ₁ ) * wa {JVAA _l ) * άη (ΑΕ ₂ ) * sin (WAA ₂ )

dT (t) = acos (dT (t) _x + dT (t) + dT (t) ₂ )

The result for the values determined in FIG. 3B is shown in FIG. 5B. The angular change dT (t) between the first and second T-turns is 6.86 °.

FIG. 6 shows the time signal dT (t) or the angle change for three consecutive T loops which follow one another at a time.

The determined time signal dT (t) can be graphically displayed over time. Thus, for a period of 200 heartbeats, Fig. 7 shows the dT (t) signal of a patient who has died within five years of a heart attack (upper curve, solid line; dT (t) _P ). It also shows the dT (t) signal of a patient who survived a five-year period after a heart attack (lower curve, unexhausted line, dT (t) _R ). In this example, the lower curve represents the reference value, with the upper curve is compared. The signals are clearly different. The deceased patient's signal shows a much more pronounced variability, which allows the diagnosis of a repolarization disorder.

Quantification of dT (t)

The time function dT (t) can be analyzed by various time and frequency domain methods. One possibility is spectral analysis; see. Fig. 8A. Another possibility is the wavelet analysis. Alternatively, the so-called "phase rectified signal averaging" - or PRSA analysis offers; see. Fig. 8B. The PRSA signal shows a clear oscillation with a wavelength of about 40 beats.

The PRSA signal can be quantified by a Haar wavelet transformation. The resulting parameter is referred to by the inventors as TWR (T-Wave Rhythmicity). FIG. 9 shows the TWR value of a patient who has survived without complications for at least five years after a myocardial infarction (left, PRSA _R ). The data were obtained shortly after the onset of myocardial infarction. In contrast, the TWR value of a patient who died within five years of a heart attack (right, PRSA _P ) is shown. The data was also obtained shortly after the onset of myocardial infarction. In both PRSA signals, there are low-frequency oscillations, ie repolarization processes of both patients are periodically modulated. However, the amplitudes of the oscillations in the PRSA signal of the deceased patient are significantly higher. The TWR value obtained by quantifying the PRSA signal quantifies the amplitude in the center of the PRSA signal and can be used as a risk parameter. In the example given, the TWR value of the survivor is 1.08 ° and the TWR value of the deceased is 6.18 °. The TWR value of the deceased is thus significantly larger than that of the surviving patient. Clinical study

The prognostic value of the method according to the invention was confirmed in a clinical study. 908 patients who had survived an acute myocardial infarction were studied. 335 patients (37%) were older than 65 years. 85 patients (9%) showed a left ventricular ejection fraction (LVEF) of <35%. 47 patients (5%) had an LVEF of <30%. 179 patients (20%) had diabetes mellitus. Eighty-six patients (9%) had a heart attack earlier.

In the second week after the acute myocardial infarction, a high-resolution (1600 Hz) three-dimensional ECG or vectorcardiogram was taken in all patients using Frank leads over 30 minutes and all data recorded on a storage medium.

Patients were followed for a period of five years. During this time, 839 patients survived. 69 patients died.

Based on the data obtained, the TWR value was determined for each patient by means of the method according to the invention. The result is shown in FIG. 10 in the form of a box plot. As can be easily seen, there is a statistically highly significant difference in TWR between both groups of patients. The deceased patients have significantly higher TWR values.

By means of methods known to the person skilled in the art, the reference value or separation value between the two groups can be determined. This is done, for example, by means of the maximization of the so-called Logrank or Mantel-Cox test. In the collective studied, the optimal cutoff value, ie the reference value, between survivors and deceased was 4.2 °. Using this cut-off value, the logrank test statistic is maximal. Patients with one TWR values> 4.2 ° are therefore considered to be at risk, and patients <4.2% are considered to be at low risk; see. Fig. 11.

FIG. 12 shows the mortality rates of patients of the investigated collective stratified according to TRW> 4.2 ° (upper curve, solid line) and <4.2 ° (lower curve, open line). Patients with TWR> 4.2 ° are much more likely to die in the aftermath of infarction, compared to patients with TWR <4.2 °.

In a multivariable Cox regression analysis, the TWR value of> 4.2 ° proves to be a strong predictor independent of conventional risk factors. The Cox regression analysis provides a statistical model for predicting 5-year mortality using the risk markers entered into the analysis. All values with a p-value of <0.05 are included in the model. The relative risk shows the relative importance of each parameter. The result of a Cox regression analysis for the clinical study performed is shown in Table 1 below.

Tab. 1: Association of risk variables with all-cause mortality;

CI = confidence interval, p = significance value, TWR = T-wave rhythmicity value, LVEF = left ventricular ejection fraction, HI = heart attack

The TWR value is the strongest parameter with a relative risk of 6.5 in this analysis. This means that the TWR value according to the invention is an extremely strong and conventional risk factors Independent predictor, which has a much greater significance than the current standard predictor LVEF.

Claims

A method for determining a change in a living entity over time periodically occurring at least three-dimensionally identifiable signal to a corresponding signal in a reference organism, the method comprising the steps of:

3. Determination of the changes dT (t) _{P of} the spatial position of the weighted main vector of each at least three-dimensionally identifiable signal with respect to the spatial position of the weighted main vector of a temporally subsequent at least three-dimensionally identifiable signal,

5. Correlation of dT (t) _P * dT (t) _R with the presence of the change.

A method according to claim 1, characterized in that in step 4 a quantification of dT (t) _P to obtain an indicator value and a corresponding quantification of dT (t) _R to obtain a reference value and a comparison of indicator value and reference value takes place, and in step 5 there is a correlation of indicator value * reference value with the presence of the change.

3. The method according to claim 1, characterized in that it is in the determination of the change in a living organism over time periodically occurring at least three-dimensional identifiable signal to a corresponding signal in a reference organism to the diagnosis of a Repolarisationsstörung in a living being.

4. The method according to claim 1 or 2, characterized in that it is at least three-dimensional identifiable signal to the development of tension in the heart during the ventricular repolarization (T-loop).

5. The method according to any one of the preceding claims, characterized in that the provided in step 1 record measured data of a vector cardiogram.

6. The method according to any one of the preceding claims, characterized in that step 2 is carried out by mathematical transformation of the Cartesian coordinates x, y, z of the at least three-dimensionally identifiable signal in the polar coordinates azimuth angle, elevation angle and radius (amplitude).

7. The method according to any one of the preceding claims, characterized in that in step 3 dT (t) _{P is determined} as an angle measure.

8. The method according to any one of the preceding claims, characterized in that in step 3, the temporal changes dT (t) _{P of} the spatial position of the weighted main vector of each at least three-dimensionally identifiable signal to the spatial position of the weighted main vector of temporally next following at least three-dimensional identifiable signal is determined.

9. The method according to any one of the preceding claims, characterized in that in step 4 dT (t) _P is analyzed by spectral analysis and a comparison with analyzed by spectral analysis dT (t) _R takes place.

10. The method according to any one of the preceding claims, characterized in that in step 4 dT (t) _P is analyzed by wavelet analysis and a comparison with analyzed by wavelet analysis dT (t) _R takes place.

11. Method according to one of the preceding claims, characterized in that, in step 4, dT (t) _{P is} transformed into a PRSAp signal by means of "phase-rectified signal averaging" (PRSA) and a comparison with a corresponding one into a PRSA _R - Signal transformed dT (t) _R takes place.

12. The method according to claim 11, characterized in that the indicator value is a measure of the amplitude in the center of the PRSA _P signal and the reference value is a measure of the amplitude in the center of the PRSA _R signal.

13. The method according to any one of the preceding claims, characterized in that the following applies in step 5: Correlation of indicator value> reference value with the presence of the change.

14. The method according to any one of the preceding claims, characterized in that in step 1 of the record at least 60, preferably at least 120, more preferably at least 180, more preferably at least 240, more preferably at least 300, more preferably at least 600, more preferably at least 900, more preferably at least 1200, most preferably at least 2000 contains three-dimensionally identifiable signals.

15. Apparatus for carrying out the method according to one of the preceding claims 4 to 14.

16. The apparatus of claim 15, characterized by a data carrier containing the data set from step 1, and an evaluation device for determining the weighted main vector for each T-loop, for determining the time function dT (t) _P ,

for quantifying the time function dT (t) _P and obtaining an indicator value,

for correlating the indicator value with a reference value, and for setting the diagnosis.

17. The apparatus of claim 16, characterized in that the evaluation device has a processor.

18. Computer program designed to carry out steps 2 to 5 of the method according to one of claims 1 to 14.

19. Computer-readable data carrier having the computer program according to claim 18.