Method and apparatus for evaluating effectiveness of antiarrhythmic based on simulation using change of ion current

Abstract

In one embodiment, an antiarrhythmic drug effect evaluation device may perform the operation of acquiring an electrogram signal measured by simulating a change in ion current of the atrium following the administration of an antiarrhythmic drug; the operation of deriving peak information included in the electrogram signal; the operation of deriving an average interval between peaks and an irregularity regarding the interval between peaks based on the peak information; and the operation of evaluating the effect of the antiarrhythmic drug on the atrium by comparing the average interval or the irregularity with the time of electrical stimulation over the entire simulation time according to a preset standard.

Description

Technology Field

[0001] The present invention relates to a technology for automatically evaluating the effects of antiarrhythmic drugs using a simulation that measures changes in ion current according to the characteristics of the antiarrhythmic drug. Background Technology

[0002] Arrhythmia refers to a condition in which electrical impulses in the heart are not generated properly or transmitted correctly, preventing regular contractions from continuing and causing the heart rate to become abnormally fast, slow, or irregular; it can be a cause of sudden death or stroke.

[0003] Treatment methods for arrhythmia include surgical therapies such as catheter ablation, which block electrical conduction by cauterizing cardiac tissue; however, there is a problem in determining which part of the heart should be treated to achieve the optimal effect. Consequently, antiarrhythmic drugs, which can treat arrhythmia with medication, are being actively utilized as a treatment method in recent years.

[0004] There are various types of such antiarrhythmic drugs, and since any type has the characteristic of regulating ion channels in heart cells, the characteristics of the ion channels can be determined in advance, allowing for the selection of an antiarrhythmic drug that can guarantee efficacy and safety for the patient. In particular, since the result of administering an antiarrhythmic drug leads to a change in ion current, the therapeutic effect can be simulated by simulating the characteristics of the selected antiarrhythmic drug. For example, by using a virtual simulation technology (Patent Registration No.: 10-1617683) that measures changes in ion current according to the characteristics of the antiarrhythmic drug, it is possible to obtain an electrogram signal of the atrium that has been changed by a virtual antiarrhythmic drug.

[0005] Meanwhile, to select the optimal antiarrhythmic agent for the treatment of atrial fibrillation using this simulation technology, the efficacy of the antiarrhythmic agent was evaluated by having an observer with expertise in electrogram (EGM) analysis directly identify abnormal signals within the electrogram.

[0006] However, existing methods for evaluating the efficacy of antiarrhythmic drugs have limitations, such as regional limitations where the observation of electrogrammatic signals in specific areas inevitably provides limited information, issues regarding noise sensitivity where errors may occur due to the user's subjective judgment because electrogrammatic data is sensitive to noise, and issues regarding labor intensity where labor is required as it relies on the observer's subjective evaluation.

[0007] Accordingly, to overcome existing limitations, there is a need for a new antiarrhythmic drug evaluation technology that is robust to noise and capable of automatically performing electro-data analysis and evaluation. Prior art literature

[0008] Korean Registered Patent Publication No. 10-1617683 Korean Registered Patent Publication No. 10-2257498 The problem to be solved

[0009] The problem that the present invention aims to solve is to provide a technology for detecting atrial fibrillation and atrial tachycardia, and for detecting the termination of atrial fibrillation caused by an antiarrhythmic drug, by analyzing electrogram (EGM) data of the atrium that simulates changes in ion current according to the characteristics of the antiarrhythmic drug.

[0010] Meanwhile, the technical problems of the present invention are not limited to those mentioned above, and other unmentioned technical problems will be clearly understood by a person skilled in the art from the description below. means of solving the problem

[0011] A method performed by an antiarrhythmic drug effect evaluation device operated by a processor according to one embodiment may include: acquiring an electrogram signal measured by simulating a change in ion current of the atrium following the administration of an antiarrhythmic drug; deriving peak information included in the electrogram signal; deriving an average interval between peaks and an irregularity regarding the interval between peaks based on the peak information; and evaluating the effect of the antiarrhythmic drug on the atrium by comparing the average interval or the irregularity with the time of electrical stimulation over the entire simulation time according to a preset standard.

[0012] Additionally, the electrical signal has K voltage values ​​mapped to K time values ​​(where K is a plurality of natural numbers), and the operation of deriving peak information is an operation of normalizing the K voltage values ​​to a preset range; and a voltage value for the i-th time value (where i is a natural number greater than 1 and less than K) among the K voltage values ​​that exceeds a predetermined threshold. a is the i-1th voltage value Greater than, and the i+1th voltage value If the condition is greater, the voltage value of the i-th time value above It may include an operation of deriving peaks; and an operation of deriving information about the time interval between adjacent peaks among the derived peaks.

[0013] In addition, the operation of deriving the above irregularity may include the operation of deriving an ShEn value that reflects the irregularity of the interval between peaks by calculating the Shannon entropy between peak intervals based on the following [Equation 1].

[0014] [Mathematical Formula 1]

[0015]

[0016] (SH(X) is the ShEn value calculated using the Shannon entropy function, X is peak interval information, N (N is a plurality of natural numbers) is the total number of peak intervals, is the i-th peak interval among N peak intervals)

[0017] Additionally, the operation of evaluating the above effect may include: an operation of evaluating that the electrical activity for the simulation has ended early if the time difference between the total simulation time for the electrical signal and the time of occurrence of the last observed peak exceeds three times the average peak interval; and an operation of designating the time of occurrence of the last observed peak as the end point of the arrhythmia due to the administration of an antiarrhythmic drug.

[0018] In addition, the operation to evaluate the above effect may include an operation to score the termination of arrhythmia based on the following [Mathematical Formula 2].

[0019] [Mathematical Formula 2]

[0020]

[0021] ( is a value that quantifies the termination of arrhythmia, is the time of occurrence of the last observed peak, is the total simulation time, (at the point of electrical stimulation)

[0022] In addition, the operation of evaluating the above effect may include an operation of evaluating the electrocardiogram signal as atrial fibrillation if the ShEn value exceeds a predetermined threshold.

[0023] In addition, the operation to evaluate the above effect may include an operation to score the duration of atrial fibrillation caused by antiarrhythmia based on the following [Equation 3].

[0024] [Mathematical Formula 3]

[0025]

[0026] ( is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is the duration of atrial fibrillation, is the total simulation time, (at the point of electrical stimulation)

[0027] In addition, the operation of evaluating the above effect may include an operation of evaluating atrial tachycardia when the ShEn value is below a predetermined threshold and the number of average peaks per minute exceeds 100.

[0028] In addition, the operation to evaluate the above effect may include an operation to score the duration of cardiac tachycardia caused by antiarrhythmia based on the following [Equation 4].

[0029] [Mathematical Formula 4]

[0030]

[0031] ( is a scored value of the duration of cardiac tachycardia caused by antiarrhythmia, is the time when cardiac tachycardia was observed, is the total simulation time, (at the point of electrical stimulation)

[0032] In addition, the operation of evaluating the above effect may include an operation of evaluating a case where the ShEn value is below a predetermined threshold (< 0.767) and the average number of peaks per minute is 100 or less as a normal rhythm.

[0033] In addition, the operation of evaluating the above effect is an operation of scoring the termination of arrhythmia based on the following [Mathematical Formula 2];

[0034] [Mathematical Formula 2]

[0035]

[0036] ( is a value that quantifies the termination of edema, is the above termination point, is the total simulation time, (at the point of electrical stimulation)

[0037] An action of scoring the duration of atrial fibrillation caused by antiarrhythmia based on the following [Mathematical Formula 3];

[0038] [Mathematical Formula 3]

[0039]

[0040] ( is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is the duration of atrial fibrillation, is the total simulation time, (at the point of electrical stimulation)

[0041] An action of scoring the duration of cardiac tachycardia caused by antiarrhythmia based on the following [Mathematical Formula 4]; and

[0042] [Mathematical Formula 4]

[0043]

[0044] ( is a scored value of the duration of cardiac tachycardia caused by antiarrhythmia, is the duration of cardiac tachycardia, is the total simulation time, (at the point of electrical stimulation)

[0045] The operation may include finally evaluating the effect of the above antiarrhythmic agent based on the following [Mathematical Formula 5].

[0046] [Mathematical Formula 5]

[0047]

[0048] ( is the final evaluation score for antiarrhythmic drugs, is a value that quantifies the termination of arrhythmia, is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is a scored value representing the duration of cardiac tachycardia caused by antiarrhythmia)

[0049] An antiarrhythmic drug effect evaluation device according to one embodiment includes a memory containing instructions; and a processor that performs a predetermined operation based on the instructions, wherein the operation of the processor may include: an operation of acquiring an electrogram signal measured by simulating a change in ion current of the atrium following the administration of an antiarrhythmic drug; an operation of deriving peak information included in the electrogram signal; an operation of deriving an average interval between peaks and an irregularity regarding the interval between peaks based on the peak information; and an operation of evaluating the effect of the antiarrhythmic drug on the atrium by comparing the average interval or the irregularity with the time of electrical stimulation over the entire simulation time according to a preset standard. Effects of the invention

[0050] The present invention can evaluate the effect of an antiarrhythmic drug on the atrium by simulating changes in atrium ion currents following the administration of an antiarrhythmic drug, obtaining measured electrogram signals to derive peak information, and comparing the average interval or irregularity between peaks with the timing of electrical stimulation over the entire simulation time.

[0051] Accordingly, the present invention can overcome the problems of regional limitations, noise sensitivity, and labor intensity of existing techniques, and enables the construction of an automated system that is robust to noise and can automatically perform analysis of electrogram signals and evaluation of antiarrhythmic drug effects.

[0052] Meanwhile, the effects of the present invention are not limited to those mentioned above, and other unmentioned technical effects will be clearly understood by a person skilled in the art from the description below. Brief explanation of the drawing

[0053] FIG. 1 is a configuration diagram of an antiarrhythmic drug effect evaluation device according to one embodiment. FIG. 2 is a flowchart showing the steps of an operation performed by an antiarrhythmic drug effect evaluation device according to one embodiment. FIG. 3 is an example of an ion current value for reflecting the characteristics of an antiarrhythmic agent in a virtual simulation according to one embodiment. FIG. 4 is a flowchart of the operation of an antiarrhythmic drug effect evaluation device deriving peak information from an electrograph signal according to one embodiment. FIG. 5 is an illustrative diagram explaining the concept of an antiarrhythmic drug effect evaluation device deriving peak information from an electrograph signal according to one embodiment. FIG. 6 is an example diagram of an operation in which an antiarrhythmic drug effect evaluation device according to one embodiment registers a queue and analyzes a patient. Figure 7 is a comparison of the results of manual analysis (A) and the evaluation (B) analyzed through the examples of the document regarding a cardiac model in which a virtual drug of dronedarone was administered and observed on actual patient data. Figure 8 is a comparison of the results of manual analysis (A) and the evaluation (B) analyzed through the example of the document regarding the electrogram signal observed after administering a virtual drug of dronedarone to actual patient data. Figure 9 shows the electrogram changes when different virtual antiarrhythmic agents are administered to the same patient, and is a result showing the time at which atrial fibrillation, termination of arrhythmia, and cardiac tachycardia are determined according to the embodiment of the present document. FIG. 10 is a comparison table of signal classification results and time between the results of manual evaluation for each of the multiple antiarrhythmic agents (A) and the results of evaluation according to the embodiment of the present document (B). Specific details for implementing the invention

[0054] Detailed information regarding the purpose, technical configuration, and resulting effects of the present invention will be more clearly understood through the following detailed description based on the drawings attached to the specification of the present invention. An embodiment according to the present invention will be described in detail with reference to the attached drawings.

[0055] The embodiments disclosed herein should not be interpreted or used to limit the scope of the invention. It is obvious to those skilled in the art that the description including the embodiments herein has various applications. Accordingly, any embodiments described in the detailed description of the invention are illustrative for better explaining the invention and are not intended to limit the scope of the invention to the embodiments.

[0056] The functional blocks shown in the drawings and described below are merely examples of possible implementations. In other implementations, other functional blocks may be used without departing from the spirit and scope of the detailed description. Additionally, while one or more functional blocks of the present invention are shown as individual blocks, one or more of the functional blocks of the present invention may be a combination of various hardware and software configurations that perform the same function.

[0057] Furthermore, the expression that it includes certain components is an “open-ended” expression that merely refers to the existence of such components and should not be understood as excluding additional components.

[0058] Furthermore, when it is stated that one component is “connected” or “joined” to another component, it should be understood that while it may be directly connected or joined to that other component, there may also be other components present in between.

[0059] Hereinafter, various embodiments of the present invention are described with reference to the accompanying drawings. However, this is not intended to limit the present invention to specific embodiments and should be understood to include various modifications, equivalents, and / or alternatives of the embodiments of the present invention.

[0060] FIG. 1 is a diagram showing the configuration of an antiarrhythmic drug effect evaluation device (100) (hereinafter referred to as 'device (100)') according to one embodiment.

[0061] Referring to FIG. 1, a device (100) according to one embodiment may each include a memory (110), a processor (120), an input / output interface (130), and a communication interface (140).

[0062] The memory (110) can store data obtained from an external device or data generated by itself. The memory (110) can store instructions that can perform the operation of the processor (120). In addition, the memory (110) can store a simulation program (e.g., Korean Registered Patent Publication No. 10-1617683) for observing changes in the ion current of the atrium following the administration of an antiarrhythmic drug, which will be described later. In addition, the memory (100) can store an electrogram signal derived according to the simulation.

[0063] The processor (120) is a computational device that controls the overall operation. The processor (120) can execute instructions stored in memory (110). According to the embodiment of this document, the operation of the device (100) of FIG. 2 described below can be understood as an operation performed by the processor (120).

[0064] The input / output interface (130) may include a hardware interface or a software interface for inputting or outputting information.

[0065] The communication interface (140) enables the transmission and reception of information through a communication network. To this end, the communication interface (140) may include a wireless communication module or a wired communication module.

[0066] The device (100) can be implemented in various forms of devices capable of performing calculations through a processor (120) and transmitting and receiving information through a network. For example, it can be implemented in the form of a server, a computer device, a portable communication device, a smartphone, a portable multimedia device, a laptop, a tablet PC, etc., but is not limited to these examples.

[0067] FIG. 2 is a flowchart of an operation performed by a device (100) according to one embodiment. The operation of the device (100) according to the embodiment of FIG. 2 can be understood as an operation performed by a processor (120).

[0068] Each step disclosed in FIG. 2 is merely a preferred embodiment for achieving the purpose of the present invention, and some steps may be added or deleted as needed, and any one step may be included in another step. The order of each operation disclosed in FIG. 2 is arranged only for ease of understanding and is not limited to a chronological order, and the order may be changed and operated differently according to the designer's choice.

[0069] Referring to FIG. 2, in step S1010, the device (100) can obtain an electrogram signal (e.g., electrogram, EGM) measured by simulating a change in the ion current of the atrium following the administration of an antiarrhythmic drug.

[0070] Antiarrhythmic drugs are various types of medications capable of treating arrhythmias. Since all types possess the characteristic of regulating ion channels in cardiac cells, the characteristics of these ion channels can be determined in advance. Below, the details of the simulation based on ion channel regulation will be explained together with Figure 3.

[0071] FIG. 3 is an example of an ion current value for reflecting the characteristics of an antiarrhythmic agent in a virtual simulation according to one embodiment.

[0072] Referring to FIG. 3, according to the characteristic that the result of administering an antiarrhythmic drug leads to a change in ion current, the device (100) can obtain an electrogram signal by reflecting a virtual antiarrhythmic drug mechanism by adjusting coefficients corresponding to each ion current to induce atrial fibrillation through a Courtemanche model, based on the information in FIG. 3, which is an ion current value to reflect the characteristics of the antiarrhythmic drug and the criteria for inducing atrial fibrillation without administering the antiarrhythmic drug.

[0073] For example, as one of the known technologies, the device (100) can acquire an electrogram signal by using a simulation technology that measures changes in ion current according to the characteristics of an antiarrhythmic drug (e.g., Korean Registered Patent Publication No. 10-1617683). Through this, the device (100) can acquire an electrogram signal of a simulated pacing region of the heart (e.g., a three-dimensional node of the left atrium) using virtual simulation, and can observe the electrogram signal of the atrium according to the administration of an antiarrhythmic drug by applying a preset electrical stimulus (e.g., ramp pacing) to the pacing region. For example, the device (100) can perform an atrial fibrillation simulation by adjusting the ion current coefficient according to changes in the concentration of major antiarrhythmic drugs such as amiodarone, sotalol, dronedarone, flecainide, and propafenone.

[0074] For example, the electrogram signal is spatiotemporal data acquired throughout the left atrium and may include information about changes in voltage values ​​over time. The electrogram signal may include time information in which electrical stimulation (e.g., ramp pacing) is applied to a pacing region (e.g., a 3D node of the left atrium) to observe the atrium's response to the administration of an antiarrhythmic drug during the entire simulation time.

[0075] The electrical signal may be continuous or discontinuous information. If the electrical signal is continuous information, the device (100) may sample the electrical signal a predetermined number of times (e.g., K, where K is a plurality of natural numbers) to obtain data in which K voltage values ​​are mapped to K time values. For ease of understanding, the following description will explain the electrical signal using K sampled data as an example.

[0076] In step S1020, the device (100) can derive peak information included in the electrical signal. An example of deriving peak information is described together with the following FIGS. 4 and 5.

[0077] FIG. 4 is a flowchart of an operation in which a device (100) derives peak information from an electrical signal according to one embodiment, and FIG. 5 is an example diagram for explaining the concept of a device (100) deriving peak information from an electrical signal according to one embodiment.

[0078] Referring to FIGS. 4 and FIGS. 5, in step S1021, the device (100) can normalize K voltage values ​​to be values ​​within a preset range (e.g., a range of voltage values ​​from 0V to 1V).

[0079] In step S1022, the device (100) has a voltage value for the i-th time value (where i is a natural number greater than 1 and less than K) that exceeds a predetermined threshold (e.g., 0.25V) among K voltage values. a is the i-1th voltage value Greater than, and the i+1th voltage value If the condition is greater, the i-th time value and voltage value It can be derived from the time the peak occurred and the peak value.

[0080] In step S1023, the device (100) can derive information regarding the time interval between adjacent peaks among the derived peaks. Accordingly, the peak information may include information regarding the time at which a peak occurred in the electrical signal, information regarding the voltage value at that time, and information regarding the time interval between adjacent peaks.

[0081] In step S1030, the device (100) can derive the average interval between peaks and the irregularity of the interval between peaks based on peak information.

[0082] For example, the device (100) can derive the ‘average interval between peaks’ by dividing the ‘total length of the time interval between peaks’ derived in step S1020 by the ‘total number of peak intervals’.

[0083] For example, the device (100) can derive an ShEn value that reflects the irregularity of the interval between peaks by calculating the Shannon entropy between peak intervals derived in step S1020 based on the following [Equation 1].

[0084] [Mathematical Formula 1]

[0085]

[0086] (SH(X) is the ShEn value calculated through the Shannon entropy function, X is a variable specifying information about peak intervals, N (N is a plurality of natural numbers) is the total number of peak intervals, is the i-th peak interval among N peak intervals)

[0087] In step S1040, the device (100) can evaluate the effect of an antiarrhythmic agent on the atrium by comparing the average interval or irregularity derived in step S1030 with the total simulation time and the time of electrical stimulation (ramp pacing). For example, the device (100) can evaluate the effect of the antiarrhythmic agent on the atrium as at least one of termination of arrhythmia, atrial fibrillation (AF), atrial tachycardia (AT), and normal sinus rhythm.

[0088] For example, in step S1040, the device (100) may evaluate that the arrhythmia symptoms for the simulation of antiarrhythmic drug administration have ended prematurely if the time difference between the total simulation time for the electro-signal signal and the time of occurrence of the last observed peak exceeds three times the average peak interval. If the electro-signal activity is evaluated as having ended prematurely, the device (100) may designate the time of occurrence of the last observed peak as the end point of the arrhythmia caused by the administration of the antiarrhythmic drug.

[0089] If the arrhythmia is evaluated as having ended early, the device (100) can score the end of the arrhythmia based on the following [Equation 2].

[0090] [Mathematical Formula 2]

[0091]

[0092] ( is a value that quantifies the termination of arrhythmia, is the time of occurrence of the last observed peak, is the total simulation time, is the time at the point of electrical stimulation)

[0093] Accordingly, is a value that quantifies the termination of arrhythmia caused by antiarrhythmic drugs, and can have a score of 0 to 1. For example, assuming the total simulation time is 32,000 ms and the time of electrical stimulation is 11,520 ms, if the occurrence of the last observed peak is observed at 11,520 ms, 1 point, if the end point was not observed or was observed at 32,000 ms It can be scored as 0 points.

[0094] For example, in step S1040, the device (100) can evaluate that the electrograph signal is atrial fibrillation if the ShEn value exceeds a predetermined threshold value (e.g., 0.767). If the electrograph signal is evaluated as atrial fibrillation, the device (100) can score the duration of the atrial fibrillation caused by antiarrhythmia based on the following [Equation 3].

[0095] [Mathematical Formula 3]

[0096]

[0097] ( is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is the duration of atrial fibrillation, is the total simulation time, is the time at the point of electrical stimulation)

[0098] Accordingly, is a value that quantifies the duration of atrial fibrillation caused by an antiarrhythmic drug, and can have a score of 0 or higher and 1 or lower. For example, if the total simulation time is 32,000 ms and the time at the start of electrical stimulation is 11,520 ms, the score can be 0 if the duration of atrial fibrillation is 20,480 ms (time from the start of electrical stimulation until the end of the simulation), and 1 if no atrial fibrillation is observed or the duration of atrial fibrillation is 0 ms.

[0099] For example, in step S1040, the device (100) may evaluate atrial tachycardia when the ShEn value is below a predetermined threshold (e.g., 0.767) and the number of average peaks per minute exceeds 100. When the electrogram signal is evaluated as atrial tachycardia, the device (100) may score the duration of cardiac tachycardia caused by antiarrhythmia based on the following [Equation 4].

[0100] [Mathematical Formula 4]

[0101]

[0102] ( is a scored value of the duration of cardiac tachycardia caused by antiarrhythmia, is the time when cardiac tachycardia was observed, is the total simulation time, is the time at the point of electrical stimulation)

[0103] Here, SAT is a value representing the time at which AT caused by an antiarrhythmic drug is observed, and is expressed as a score between 0 and 1. For example, if the time at which AT is observed is 11,520 ms (time after ramp pacing), it may be scored as 0, and if AT is not observed or AT is observed at 32,000 ms, it may be scored as 0.

[0104] Accordingly, is a value that quantifies the duration of cardiac tachycardia caused by an antiarrhythmic drug, and can have a score of 0 to 1. For example, if the total simulation time is 32,000 ms and the time at the start of electrical stimulation is 11,520 ms, the score is 0 if the time at which cardiac tachycardia is observed is 11,520 ms (time after electrical stimulation), and 1 if cardiac tachycardia is not observed or the time at which cardiac tachycardia is observed is 32,000 ms.

[0105] For example, in step S1040, the device (100) can evaluate a normal rhythm when the ShEn value is below a predetermined threshold value (e.g., 0.767) and the number of average peaks per minute is 100 or less.

[0106] In step S1040, the device (100) can finally evaluate the effect of an antiarrhythmic agent based on the following [Equation 5] according to the classification of termination, atrial fibrillation (AF), atrial tachycardia (AT), and normal sinus rhythm described above.

[0107] [Mathematical Formula 5]

[0108]

[0109] ( is the final evaluation score for antiarrhythmic drugs, is a value that quantifies the termination of arrhythmia, is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is a scored value representing the duration of cardiac tachycardia caused by antiarrhythmia)

[0110] Accordingly, the device (100) can calculate the V value for various antiarrhythmic agents, and can evaluate that the higher the V value, the more effective the antiarrhythmic agent is.

[0111] FIG. 6 is an example diagram of an operation in which a device (100) according to one embodiment registers a queue and analyzes a patient.

[0112] Referring to FIG. 6, the device (100) can provide a user interface to an administrator to provide a function to register patients to be analyzed in a queue, and the registered patients can be analyzed according to antiarrhythmic ion current conditions. The administrator can specify the queue and monitor the progress of the simulation through a user interface such as FIG. 6.

[0113] FIG. 7 is a comparison of the results of manual analysis (A) and the evaluation (B) analyzed through the examples of the document regarding a cardiac model observed after administering a virtual drug of dronedarone to actual patient data (e.g., the observation technique of Korean Registered Patent Publication No. 10-2257498 may be used). FIG. 8 is a comparison of the results of manual analysis (A) and the evaluation (B) analyzed through the examples of the document regarding an electrogram signal observed after administering a virtual drug of dronedarone to actual patient data.

[0114] Referring to FIGS. 7 and FIGS. 8, according to the result of a manual expert evaluation of the time at which atrial fibrillation occurred (A), the time was evaluated to be 6,300 ms, and according to the result according to the embodiment of this document (B), the time at which atrial fibrillation occurred was determined to be 6,220 ms, so it can be confirmed that a time similar to the expert evaluation can be automatically determined.

[0115] Figure 9 shows the electrogram changes when different virtual antiarrhythmic agents are administered to the same patient, and is a result showing the time at which atrial fibrillation, termination of arrhythmia, and cardiac tachycardia are determined according to the embodiment of the present document.

[0116] FIG. 10 is a comparison table of signal classification results and time between the results of manual evaluation for each of the multiple antiarrhythmic agents (A) and the results of evaluation according to the embodiment of the present document (B).

[0117] Referring to FIG. 10, both the manual evaluation result (A) and the evaluation result according to the embodiment of this document (B) determine the fastest electrical activity termination when 5 ml of amiodarone is applied, and the same evaluation is performed for other drugs, confirming that the embodiment of this document shows the same level as the expert evaluation.

[0118] According to the above-described embodiment, the present invention can obtain measured electrogram signals by simulating changes in ion current of the atrium following the administration of an antiarrhythmic agent to derive peak information, and evaluate the effect of the antiarrhythmic agent on the atrium by comparing the average interval or irregularity between peaks with the electrical stimulation time relative to the total simulation time.

[0119] Accordingly, the present invention can overcome the problems of regional limitations, noise sensitivity, and labor intensity of existing techniques, and enables the construction of an automated system that is robust to noise and can automatically perform analysis of electrogram signals and evaluation of antiarrhythmic drug effects.

[0120] The various embodiments of this document and the terms used therein are not intended to limit the technical features described in this document to specific embodiments, and should be understood to include various modifications, equivalents, or substitutions of said embodiments. In connection with the description of the drawings, similar reference numerals may be used for similar or related components. The singular form of a noun corresponding to an item may include one or more items unless the relevant context clearly indicates otherwise.

[0121] In this document, each of the phrases such as “A or B,” “at least one of A and B,” “at least one of A or B,” “A, B or C,” “at least one of A, B and C,” and “at least one of A, B, or C” may include all possible combinations of items listed together in the corresponding phrase. Terms such as “1,” “2,” or “first” or “second” may be used simply to distinguish a component from another component and do not limit the components in any other aspect (e.g., importance or order). Where any (e.g., 1st) component is referred to as “coupled” or “connected” to another (e.g., 2nd) component, with or without the terms “functionally” or “communicationly,” it means that the component may be connected to the other component directly (e.g., wired), wirelessly, or through a third component.

[0122] As used in this document, the term "module" may include a unit implemented in hardware, software, or firmware, and may be used interchangeably with terms such as logic, logic block, component, or circuit. A module may be a component formed integrally, or a minimum unit of a component or part thereof that performs one or more functions. For example, according to one embodiment, a module may be implemented in the form of an application-specific integrated circuit (ASIC).

[0123] Various embodiments of this document may be implemented as software (e.g., a program) comprising one or more instructions stored in a storage medium (e.g., memory) that can be read by a device (e.g., an electronic device). The storage medium may include random access memory (RAM), a memory buffer, a hard drive, a database, erasable programmable read-only memory (EPROM), electrically erasable read-only memory (EEPROM), read-only memory (ROM), and / or the like.

[0124] Additionally, the processor of the embodiments of this document may call at least one instruction among one or more instructions stored from a storage medium and execute it. This enables the device to operate to perform at least one function according to at least one called instruction. Such one or more instructions may include code generated by a compiler or code that can be executed by an interpreter. The processor may be a general-purpose processor, a Field Programmable Gate Array (FPGA), an Application Specific Integrated Circuit (ASIC), a Digital Signal Processor (DSP), and / or the like.

[0125] A device-readable storage medium may be provided in the form of a non-transitory storage medium. Here, 'non-transitory' simply means that the storage medium is a tangible device and does not contain signals (e.g., electromagnetic waves), and this term does not distinguish between cases where data is stored semi-permanently and cases where it is stored temporarily.

[0126] Methods according to the various embodiments disclosed in this document may be provided as part of a computer program product. The computer program product may be traded between a seller and a buyer as a product. The computer program product may be distributed in the form of a device-readable storage medium (e.g., compact disc read-only memory (CD-ROM)), or distributed online (e.g., download or upload) through an application store (e.g., Play Store) or directly between two user devices (e.g., smartphones). In the case of online distribution, at least a portion of the computer program product may be temporarily stored or temporarily created on a device-readable storage medium, such as a manufacturer's server, an application store's server, or the server's memory.

[0127] According to various embodiments, each component (e.g., module or program) of the described components may include a singular or multiple entities. According to various embodiments, one or more of the components or operations of the aforementioned components may be omitted, or one or more other components or operations may be added. Generally or additionally, multiple components (e.g., module or program) may be integrated into a single component. In this case, the integrated component may perform one or more functions of each of the components of the multiple components in the same or similar manner as they were performed by the corresponding component among the multiple components prior to integration. According to various embodiments, operations performed by a module, program, or other component may be executed sequentially, in parallel, iteratively, or heuristically; one or more of the operations may be executed in a different order; omitted; or one or more other operations may be added. Explanation of the symbols

[0128] 100: Device 110: Memory 120: Processor 130: Input / Output Interface 140: Communication interface

Claims

Claim 1 A method performed by an antiarrhythmic drug effect evaluation device operated by a processor, comprising: acquiring an electrogram signal measured by simulating a change in ion current of the atrium following the administration of an antiarrhythmic drug; deriving peak information included in the electrogram signal; deriving an average interval between peaks and an irregularity regarding the interval between peaks based on the peak information; and evaluating the effect of the antiarrhythmic drug on the atrium by comparing the average interval or the irregularity with the time of electrical stimulation over the entire simulation time according to a preset standard. Claim 2 In claim 1, the electrical signal has K voltage values ​​mapped to K time values ​​(K is a plurality of natural numbers), and the operation of deriving peak information is an operation of normalizing the K voltage values ​​to a preset range; and a voltage value for the i-th time value (i is a natural number greater than 1 and less than K) among the K voltage values ​​that exceeds a predetermined threshold. a is the i-1th voltage value Greater than, and the i+1th voltage value If the greater condition is satisfied, the voltage value of the i-th time value above A method comprising: an operation of deriving a peak; and an operation of deriving information about the time interval between adjacent peaks among the derived peaks. Claim 3 In claim 1, the operation of deriving the irregularity includes the operation of deriving an ShEn value that reflects the irregularity of the interval between peaks through the calculation of Shannon entropy between peak intervals based on the following [Equation 1], [Equation 1] (SH(X) is the ShEn value calculated using the Shannon entropy function, X is peak interval information, N (N is a plurality of natural numbers) is the total number of peak intervals, is the i-th peak interval among N peak intervals) method. Claim 4 A method according to claim 3, wherein the operation of evaluating the effect comprises: an operation of evaluating that the electrical activity for the simulation has ended prematurely if the time difference between the total simulation time for the electrical signal and the time of occurrence of the last observed peak exceeds three times the average peak interval; and an operation of designating the time of occurrence of the last observed peak as the end point of the arrhythmia due to the administration of an antiarrhythmic agent. Claim 5 In paragraph 4, the operation for evaluating the above effect includes the operation of scoring the termination of arrhythmia based on the following [Mathematical Formula 2], [Mathematical Formula 2] ( is a value that quantifies the termination of arrhythmia, is the time of occurrence of the last observed peak, is the total simulation time, The electrical stimulation timing) method. Claim 6 In claim 5, the operation of evaluating the above effect includes an operation of evaluating the electrocardiogram signal as atrial fibrillation when the ShEn value exceeds a predetermined threshold value. Claim 7 In claim 6, the operation for evaluating the above effect includes the operation of scoring the duration of atrial fibrillation caused by antiarrhythmia based on the following [Equation 3], [Equation 3] ( is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is the duration of atrial fibrillation, is the total simulation time, The electrical stimulation timing) method. Claim 8 In paragraph 3, the operation of evaluating the above effect includes an operation of evaluating the case where the ShEn value is below a predetermined threshold and the number of average peaks per minute exceeds 100 as atrial tachycardia. Claim 9 In claim 8, the operation for evaluating the above effect includes the operation of scoring the duration of cardiac tachycardia caused by antiarrhythmia based on the following [Equation 4], [Equation 4] ( is a scored value of the duration of cardiac tachycardia caused by antiarrhythmia, is the time when cardiac tachycardia was observed, is the total simulation time, The electrical stimulation timing) method. Claim 10 A method according to claim 3, wherein the operation of evaluating the above effect includes evaluating the case where the ShEn value is below a predetermined threshold value (< 0.767) and the number of average peaks per minute is 100 or less as a normal rhythm. Claim 11 In claim 1, the operation for evaluating the above effect is an operation for scoring the termination of arrhythmia based on the following [Mathematical Formula 2]; [Mathematical Formula 2] ( is a value that quantifies the termination of edema, is the above termination point, is the total simulation time, ...is the action of scoring the duration of atrial fibrillation caused by antiarrhythmia based on [Equation 3] (at the point of electrical stimulation); [Equation 3] ( is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is the duration of atrial fibrillation, is the total simulation time, ...is the action of scoring the duration of cardiac tachycardia caused by antiarrhythmia based on [Equation 4] (at the point of electrical stimulation); and [Equation 4] ( is a scored value of the duration of cardiac tachycardia caused by antiarrhythmia, is the duration of cardiac tachycardia, is the total simulation time, [Equation 5] including the operation of finally evaluating the effect of the above antiarrhythmic agent based on [Equation 5] (at the time of electrical stimulation). ( is the final evaluation score for antiarrhythmic drugs, is a value that quantifies the termination of arrhythmia, is a scored value of the duration of atrial fibrillation caused by antiarrhythmia, is a method that scores the duration of cardiac tachycardia caused by antiarrhythmia. Claim 12 An antiarrhythmic drug effect evaluation device comprising: a memory containing instructions; and a processor that performs a predetermined operation based on the instructions, wherein the operation of the processor includes: an operation of obtaining an electrogram signal measured by simulating a change in ion current of the atrium following the administration of an antiarrhythmic drug; an operation of deriving peak information included in the electrogram signal; an operation of deriving an average interval between peaks and an irregularity regarding the interval between peaks based on the peak information; and an operation of evaluating the effect of the antiarrhythmic drug on the atrium by comparing the average interval or the irregularity with the time of electrical stimulation for the entire simulation time according to a preset standard.

Images