Patent Description:
Devices for recording electrical activity of heart, electrocardiogram or ECG, are commonly used in cardiology for heart disease diagnostic. Standard ECG monitors provide an ECG output signal in a frequency range of up to about <NUM>. High-resolution ECG monitors with a higher sampling rate <NUM>-<NUM> are available on the market to a limited extent. State of art of high-frequency ECG analysis is described in the study of <NPL>. Morphology of the QRS complex in the band from <NUM> up to <NUM>, i. centralization, conceivably broadening and bifurcation of amplitude peaks, often defined by means of RAZ (Reduced Area Zone) parameters, serves for diagnostics of pathological phenomena in myocardium, in particular of ischemic heart disease.

Recently, the inventors applied high-frequency electrocardiography (HF-ECG, <NUM>-<NUM>) to compute ventricular electrical delay (VED) determined in <NUM> left bundle branch block (LBBB) patients - <NPL>. The results showed that VED predicts survival in biventricular resynchronization patients in a more reliable manner than the conventional QRS-derived parameters. A more recent study indicated that VED might be a more useful predictor for cardiac resynchronization therapy response than ECG characteristics of strict LBBB, <NPL>. The concept with a single-band ultra-high-frequency (<NUM>-<NUM>) <NUM>-lead ECG by<NPL> presented measures of electrical depolarization patterns and ventricular electrical dyssynchrony. Method of measuring and analyzing the ultra-high-frequency signals of myocardial activity and their processing to time numerical parameters that describe the electrical ventricular dyssynchrony was described by the inventors in the <CIT>. See also<NPL>.

The aim of the present invention is to provide a method and an apparatus for processing of signals obtained from broad-band ultra-high-frequency oscillations generated by myocardium (UHF-ECG), i. the ECG components in frequency ranges within the <NUM>-<NUM> range, which would allow to accurately identify time distribution of ventricular depolarization in order to reliably diagnose heart abnormalities and pathologies which can effectively be treated by cardiac pacing.

The aim of the invention is achieved with a method of processing of multichannel broad-band ultra-high-frequency electrocardiogram, which comprises the following steps:.

In some preferred embodiments, the method may further comprise the step of calculating a final average or median envelope from all signal average or median envelopes of the said at least two channels.

First temporal duration of the signal average or median envelope is designated herein as Vdi Second temporal duration of the signal average or median envelope is designated herein as AVdi.

The Vdi and AVdi define the local depolarization duration of heart ventricles in units of time. Vdi and AVdi have different values when application of the threshold level (horizontal line) generates two or more peaks. Vd or AVd parameters may be calculated as mean or median value from Vdi or AVdi from the channels. The Vd or AVd parameters express the average depolarization activation time.

In one preferred embodiment, the method comprises further calculating a standard deviation of AVdi or Vdi values from the channels - the standard deviation is designated herein as SDVd. The SDVd expresses variability of local depolarization activation duration. A higher SDVd parameter indicates the simultaneous occurrence of fast and slow depolarization speed areas.

In one preferred embodiment of the invention, the signals are signals recorded in channels of V1, V2, V3, V4, V5, V6 electrocardiography leads or V1, V2, V3, V4, V5, V6, V7 and V8 electrocardiography leads.

In a preferred embodiment of the invention, a ventricular depolarization matrix is constructed so that each row of ventricular depolarization matrix is represented by a signal normalized average or median envelope for one of the said at least two ECG channels. Minimal and maximal value in each row of ventricular depolarization matrix is detected, the minimal value is assigned to a first color, the maximal value is assigned to a second color. The values between minimum and maximum are assigned colors in the color range from the first color to the second color with linear or nonlinear color transition. Color representation of the ventricular depolarization matrix obtained using the assigned color forms a ventricular depolarization map (VDM). The ventricular depolarization map provides an image of the depolarization activity distribution over time and ventricular volume. From the ventricular depolarization map, the timing and duration of depolarizing activity in single ECG channel can be assessed easily. At the same time, it is possible to compare the timing of depolarization activity between individual channels.

In one preferred embodiment of the invention, the method further comprises a step of calculating an activation time (ATi) as time position of the center of mass of signal normalized average or median envelopes above the horizontal line crossing signal normalized average or median envelopes at <NUM>-<NUM> percent of the maximum of signal normalized average or median envelopes or time position of maximal value of signal normalized average or median envelopes, and subsequently calculating activation dyssynchrony (DYS) as time difference between activation times of two ECG channels. The DYS parameter indicates a time delay of ventricular depolarization between any two ECG channels. The relevant value is the highest value achieved for any combination of two channels used in the method of the invention.

In a preferred embodiment of the invention, the method further comprises a step of calculating relative activation dyssynchrony (RDYS) by dividing the activation dyssynchrony value DYS by Vd or AVd values. The RDYS parameter indicates the relationship between dyssynchrony and the speed of depolarization propagation. A higher RDYS value in patients prior to cardiac resynchronization device implantation indicates a potential positive response.

In one preferred embodiment of the invention, the method further comprises a step of calculating cumulative activation dyssynchrony and depolarization duration (PDYS) by adding the value of DYS and the value of Vd or AVd.

In one preferred embodiment of the invention, the method further comprises a step of calculating relative activation dyssynchrony variability SRDYS by dividing the dyssynchrony value DYS by the SDVd parameter. The SRDYS parameter indicates the relationship between dyssynchrony and the inter-lead variability of depolarization propagation speed.

The present invention further provides an apparatus for processing electrocardiographic signal. Said apparatus comprises:.

The imaging unit is preferably configured to display the VDM and/or more parameters selected from Vdi, AVdi, ATi, DYS, Vd, AVd, SDVd, RDYS, PDYS and SRDYS.

Using the UHF-ECG processing apparatus and the method of processing the measured UHF-ECG signal, it is possible to diagnose various heart abnormalities and pathologies, which can be effectively treated by cardiac pacing. For successful cardiac pacing treatment, the time distribution of ventricular depolarization should be accurately identified. The present invention introduces a new technology for accurate determining of depolarization map that allows estimating new parameters for measuring the duration of depolarizing activity at the individual sites of the heart ventricles.

The invention will be further illustrated using exemplary embodiments, and with reference to the figures.

Object of the invention is a method of processing of multichannel broad-band ultra-high-frequency electrocardiogram.

The broad-band ultra-high-frequency electrocardiogram is a plurality of signals recorded by a plurality of measurement electrodes and presented as a plurality of signals in channels. The signals are measured in a frequency range above <NUM>. Currently, the signals are typically measured in frequency ranges starting from <NUM> and up to <NUM>, but any measuring frequency range is compliant with the present invention.

Typically, <NUM> to <NUM> channels are used. Signals from the leads V1-V6 or V1-V8 are preferred for this invention. The signals are a dependency of electrical potential (voltage) and time.

The method processes electrocardiogram comprising signals from at least two channels. Signals from the leads V1-V6 or V1-V8 are preferred. Signals from all channels, or signals only from some channels can be used in the method of the invention.

Preferably, the electrocardiogram is digitized. For example, the parameters of the digitizer may be <NUM> bits word length and a sampling rate of <NUM>. Other digitization parameters may be used, as known to the person skilled in the art.

The signal in each channel is recorded in a total frequency range of above <NUM>, preferably <NUM> to <NUM>, and can be divided into several frequency ranges.

In the following text, the channels will be designated as "CHi" which means "the i-th channel". The frequency ranges will be designated as "Fj" which means "the j-th frequency range". "CHiFj" means "the j-th frequency range in the i-th channel".

At least two frequency ranges are selected in each of the said at least two channels. The frequency ranges are frequency bands above the frequency of <NUM>. Width of each frequency range may preferably be from <NUM> to <NUM>. The frequency ranges are preferably the same in each channel.

An envelope (EnvCHiFj) of the signal is calculated for each frequency range in each channel.

An envelope is a smooth curve outlining the extremes of the oscillating signal. In this invention, the upper envelope is considered as envelope, i.e., the curve outlining the upper extremes of the signal. The envelope may be an amplitude envelope or a power envelope. The amplitude envelope is an envelope outlining the amplitude extremes of the signal. The power envelope is an envelope outlining the power extremes of the signal (power = amplitude squared).

In preferred embodiments, the amplitude or power envelopes of the ECG channel are calculated using Hilbert transformation, or the amplitude envelopes of the ECG channel are calculated by filtration, conversion of the signal obtained in this way into an absolute value and smoothing it, or the power envelopes of the ECG channel are calculated by filtration, raising the ECG signal to the power of two and smoothing it.

The calculated envelope of the signal in each frequency range in each channel into QRS complex segment envelopes, wherein a QRS complex segment envelope is a portion of the envelope of the signal, said portion corresponding to one QRS complex, i.e., outlining one QRS complex.

QRS complex segment envelope is preferably a portion of the envelope of the signal which starts at least <NUM>, or <NUM> to <NUM>, or <NUM> to <NUM>, or <NUM> to <NUM> before the position of the QRS complex, and ends at least <NUM>, or <NUM> to <NUM>, or <NUM> to <NUM>, or <NUM> to <NUM> after the position of the QRS complex. The position of the QRS complex is the temporal center of the QRS complex. The position of QRS complex can be detected by algorithms known to the person skilled in the art. An example of the position of the QRS complex and of QRS complex segment is shown in <FIG> and <FIG>.

An average or median envelope (AvgEnvCHiFj) is then computed from the QRS complex segment envelopes within each of the frequency ranges, in each of the channels. This step increases a signal-to-noise ratio for each frequency range in each channel (<FIG>).

Baseline correction may optionally be performed for each average or median envelope by subtracting mean (average) or median value from a temporal interval in which QRS complex is not present to remove noise background. Baseline correction is particularly useful if in the following step of normalization, integral is used.

The average or median envelope are normalized to obtain a normalized average or median envelope (NormAvgEnvCHiFj) for each frequency range of the signal from each channel. The normalization is performed by dividing the average or median envelope of each frequency range of the signal from each channel by its integral or by a maximal value reached in the average or median envelope. The integral or the maximal value are calculated within an interval of minimum of <NUM> before the position of QRS complex and minimum of <NUM> after the position of QRS complex. One normalized average or median envelope (NormAvgEnvCHiFj) is obtained for each frequency range in each channel (<FIG>).

Calculations of average, median or normalization are performed in the sequence of points whose time distance from the QRS complex is equal. In other words, each point (e.g., sampling point) of the average, median or normalized envelope is calculated as an average, median or normalized value, respectively, of the points in the same temporal position of all envelopes over which the calculation of the average, median or normalization is performed.

Signal average or median envelope (NormAvgEnvCHi) is calculated from the normalized average or median envelopes of all frequency ranges within each channel. The calculation is performed by averaging or determining median of normalized average or median envelopes from all frequency ranges from the channel CHi. This calculation is performed in each channel, and one signal average or median envelope is obtained for one channel (<FIG>).

First temporal duration (Vdi) of the signal average or median envelope is calculated as time length of a horizontal line crossing the signal average or median envelope with a horizontal line at a level corresponding to <NUM>-<NUM> percent, preferably <NUM>-<NUM> percent, more preferably <NUM> to <NUM> percent, of the maximum value of the signal average or median envelope (<FIG>).

The time length is calculated as distance in units of time from the first intersection of the NormAvgEnvCHi with the horizontal line at the corresponding level to the second intersection of the NormAvgEnvCHi with the horizontal line at the corresponding level. Depending on the selected level, a third and fourth intersection of the NormAvgEnvCHi with the horizontal line at the corresponding level may occur, and then the distance between the third and fourth intersection is added to the distance between the first and second intersection.

Second temporal duration (AVdi) of the signal average or median envelope (NormAvgEnvCHi) is calculated as time difference between the first and the last crossing of the signal average or median envelope with a horizontal line at a level corresponding to <NUM>-<NUM>, preferably <NUM>-<NUM> percent, more preferably <NUM> to <NUM> percent, percent of the maximum of the signal average or median envelope (<FIG>).

The time length is calculated as distance in units of time from the first intersection of the NormAvgEnvCHi with the horizontal line at the corresponding level to the last intersection of the NormAvgEnvCHi with the horizontal line at the corresponding level.

Optionally, a final average or median envelope (NormAvgEnv) is calculated as an average or median from all signal average or median envelopes (NormAvgEnvCHi) (<FIG>).

Finally, local depolarization duration of heart ventricles is determined in units of time as the first temporal duration, and/or determination the total local depolarization duration of heart ventricles in units of time as the second temporal duration.

The main field of application of the invention is cardiac pacing. Cardiac pacing has been the standard treatment for severe bradyarrhythmia for decades. It is a reliable, proven method with a generally low incidence of complications. It relies on the stimulation of the heart chambers of patients via electrodes connected to the implantable pulse generator (IPG). The electrical pulse generated in the IPG is delivered to the heart through the leads and activates myocardial cells to provide electromechanical interaction with resulting myocardial contraction.

Direct pacing of the myocardium of heart ventricles is a clinically preferred method of cardiac pacing. In this situation, electrical pulse causes excitement of myocardial cells in close relation to the lead tip and incurred electrical activity is spreading as an electrical wave-front to adjacent regions of heart ventricles. Contrary to the physiological situation, where the electrical impulse is spreading fast through the conductive system (<NUM>-<NUM>/s) and results in synchronous ventricular activation/contraction, trans-myocardial cell to cell conduction can be more than ten times slower (<NUM>,<NUM>-<NUM>,<NUM>/s). It is resulting in slow electrical wave-front propagation in ventricular myocardium and delayed activation of distant regions related to the site of pacing. In many patients, single-chamber stimulation can result in electromechanical dyssynchrony of heart ventricles with resulting heart failure.

Biventricular pacing was developed as a method of electrical resynchronization of heart ventricles in patients with their dyssynchrony due to bundle branch block. It showed to improve the cardiac output by resynchronization of ventricular electromechanical activity and to improve outcome in patients with heart failure. Although an overwhelming number of procedures were performed worldwide since the method was introduced, the fact is that a significant portion of patients does not positively respond to the therapy. One of the reasons is the imperfect electrical resynchronization provided by biventricular pacing as it relays on myocardial pacing from the right and left ventricle. Slower depolarization of ventricular myocytes is aggravated by non-physiological electrical wave-front propagation (epi-endo direction) caused by pacing from the left ventricular lead placed in the branch of coronary sinus.

In recent years, new techniques of permanent cardiac pacing were introduced. They are His bundle, left bundle branch, and left ventricular septal pacing - all together can be designated as conductive system pacing techniques. They offer more physiological ventricular activation as they primarily activate parts of the conductive system, and, as such, they provide fast myocardial depolarization.

Clinical applications of the broad-band UHF-ECG signal processing with a focus on the parameters of the speed of myocardial depolarization - Vdi, AVdi, Vd and AVd - are introduced within the framework of the present invention.

Vdi and AVdi parameters provide essential information about the speed of the myocardial depolarization in the myocytes adjacent to the specific lead. As shown below, it is different in healthy patients compared to patients with the conduction problem in the left or right Tawara branch, and also it is different during different types of ventricular pacing (myocardial vs. conductive system vs. epicardial pacing). Such information cannot be obtained from the <NUM>-lead ECG and QRS complex duration.

Vd or AVd parameters are calculated as a mean or median value from Vdi or AVdi from selected ECG channels. The Vdi and AVdi parameters are the same if the selected threshold line passes through the NormAvgEnvCHi without interruption (<FIG>, left panel). If there are separate peaks in NormAvgEnvCHi, the threshold line is interrupted (<FIG>, right panel). In that case, the Vdi and AVdi parameters have a different value. This difference is also reflected in Vd and AVd parameters. Different values of Vd and AVd indicate the existence of multiple activations in one or more ECG leads related to right ventricle free wall and septal different activation.

RDYS parameter is calculated as a division of dyssynchrony value DYS by Vd or AVd parameters (<FIG>). High RDYS value especially in records before pacing device implantation or during pacing device switched off indicates a potential positive response to resynchronization (<FIG>). PDYS parameter is calculated so that the value of DYS is added to the value of Vd or AVd. High PDYS value in patients especially during cardiac resynchronization therapy indicates a potential less positive or even negative resynchronization response (<FIG>).

The examples of clinical application given in this text are based on the following ECG recording and processing configuration:
ECG signal was recorded with sampling frequency <NUM> and dynamic range of <NUM> bits (<NUM> nV resolution) and a frequency range of <NUM>. ECG data was collected over <NUM>-<NUM> minutes in a resting supine position with a standard <NUM>-lead ECG setup. For each precordial lead (eight ECG channels V1-V8), the amplitude envelopes were computed in sixteen frequency bands F1- F16: <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, <NUM>-<NUM>, and <NUM>-<NUM> using the Hilbert transform. Amplitude envelopes EnvCHiFj were calculated and then segmented by Ra wave annotation (determination of QRS position) within the QRS complex to obtain QRS complex segment envelopes. In each frequency band Fj of each ECG channel CHi, the median amplitude envelopes were computed as the median value of the points of the QRS complex segment envelopes (AvgEnvCHiFj, <FIG>). Baseline correction was performed. Baseline correction was computed by subtracting mean from an interval of <NUM>-<NUM> after the position of Ra from AvgEnvCHiFj. Thereafter, the median amplitude envelopes of each frequency band were normalized. Normalization was performed using the integral, which was calculated in the interval of <NUM> before the QRS position and <NUM> after the QRS position. Subsequently, all median envelope values were divided by this integral (NormAvgCHiFj). This procedure achieves that the integral in all frequency bands is the same. Normalization in the various frequency domains was used to avoid that the larger low-frequency amplitudes would dominate the weak high-frequency amplitudes during the subsequent averaging over frequencies.

The following examples show the relationship between these parameters during different types of pathologies and stimulations:.

Claim 1:
A method of processing of electrocardiogram, which comprises the following steps:
- providing an electrocardiogram comprising signals in at least two channels;
- selecting at least two frequency ranges of the signal in each of the said at least two channels;
- calculating an envelope for the signal in each frequency range in each channel;
- dividing the calculated envelope of the signal in each frequency range in each channel into QRS complex segment envelopes;
- computing an average or median envelope as an average or median of QRS complex segment envelopes for each frequency range in each channel;
- normalizing the average or median envelope to obtain a normalized average or median envelope for each frequency range in each channel; characterised in that the normalization is performed by dividing the average or median envelope of each frequency range in each channel by its integral or by a maximal value reached in the average or median envelope, in each frequency range and each channel separately, wherein the integral or the maximal value are calculated within an interval of a minimum of <NUM> before the position of QRS complex and minimum <NUM> after the position of QRS complex; wherein the position of the QRS complex is the temporal center of the QRS complex;
- calculating a signal average or median envelope from the normalized average or median envelopes of all frequency ranges within each channel; and
- calculating a first temporal duration (Vdi) of the signal average or median envelope as time length of a horizontal line crossing the signal average or median envelope, wherein the horizontal line is at a level within <NUM>-<NUM> percent of the maximum value of the signal average or median envelope; and/or
- calculating a second temporal duration (AVdi) of the signal average or median envelope as time difference between the first and the last intersection of the signal average or median envelope with the horizontal line, wherein the horizontal line is at a level within <NUM>-<NUM> percent of the maximum value of the signal average or median envelope or of the final average or median envelope;
- determining the local depolarization duration of heart ventricles in units of time as the first temporal duration, and/or determination the total local depolarization duration of heart ventricles in units of time as the second temporal duration.