CN116829059A

CN116829059A - Dynamic electrocardiogram patch apparatus and method

Info

Publication number: CN116829059A
Application number: CN202280014121.4A
Authority: CN
Inventors: 布拉尼斯拉夫·瓦伊迪克; 多林·帕内斯库; 博斯科·波约维奇; 柳普乔·哈德兹维斯基; 弗拉丹·武克切维奇; 乌鲁斯·米特洛维奇; 马里安·密勒堤
Original assignee: Heartbeam Inc
Current assignee: Heartbeam Inc
Priority date: 2021-01-04
Filing date: 2022-01-04
Publication date: 2023-09-29

Abstract

Methods and apparatus, including devices and systems, for remote detection and/or diagnosis of Acute Myocardial Infarction (AMI). In particular, described herein are handheld devices and adhesive devices having an electrode configuration that is capable of recording three orthogonal ECG lead signals in an orientation-specific manner and transmitting those signals to a processor. The processor may be remote or local and it may automatically or semi-automatically detect AMI, atrial fibrillation or other heart disorders based on analysis of deviations of the recorded 3 cardiac signals from previously stored reference recordings.

Description

Dynamic electrocardiogram patch apparatus and method

Priority claim

The present application claims priority from U.S. patent application Ser. No. 17/202,299 entitled "ELECTROCARDIORGAM PATCH DEVICES AND METHOD", filed on 3/15 of 2021, and U.S. provisional patent application Ser. No. 63/133,669 entitled "AMBULATORY ELECTROCARDIOGRAM PATCH DEVICES AND METHOD", filed on 4 of 2021, each of which is incorporated herein by reference in its entirety.

Incorporated by reference

All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

FIELD

The methods and apparatus (e.g., systems, devices, etc.) described herein may generally relate to electrocardiography (Electrocardiography).

Background

Acute myocardial infarction (AMI, also known as heart attack) remains a major cause of mortality in developed countries. It is crucial to find an accurate and cost-effective solution for AMI diagnostics. Survival of patients with AMI may depend largely on reducing treatment delay, particularly the time between symptom onset and medical treatment time. Techniques that enable early AMI diagnosis after the appearance of AMI symptoms (e.g., in the patient's home or wherever the patient may be), can significantly reduce AMI mortality.

In the AMI environment, a conventional 12-lead ECG is not only the most important information, but it is also almost equally important in combination with all other information. Thus, techniques for early AMI diagnosis may rely on ECG recordings. ECG recording can be performed by the patient himself, but such a technique would need to overcome the problem of the complex application of 12-lead ECG electrodes and would need to implement AMI detection based on automated software.

Electrocardiogram (ECG) data recording is well known in the art as an acquisition of bioelectric signals for the detection of heart condition status. Typically, before recording is performed, feature points on the patient's body are identified and the electrodes are positioned with reference to these points. During the recording procedure (procedure), the voltage between the two characteristic points is measured and the corresponding signal is called the ECG lead. Conventional ECG uses 10 electrodes to record 12 leads, and 12 lead ECG (12L ECG) is a standard widely used in cardiac diagnostics.

It has long been recognized that emergency cardiac diagnostics would be beneficial to enable a patient wherever he is and to record his own ECG and send it via a commercial telecommunications network (cellular or similar network) to a cardiologist who is in a remote diagnostic center. Based on the received ECG and talking to the patient, the on-duty cardiologist can determine whether the patient's status requires urgent medical intervention and take action accordingly. In the emergency cardiac diagnostic concept, there are a number of patents and products that provide different solutions for recording and transmitting ECG signals. The simplest of these devices uses only a single "lead" or pair of electrodes. However, a device that records only one ECG lead may only be used for rhythm disorders. Because the ECG changes required to detect AMI may occur as little as only two of the 12 leads of a conventional electrocardiogram, it may be difficult to reliably detect AMI using only a single lead (or in some cases only a few leads) reliably and thoroughly. Furthermore, it is also not reasonable to record a complete 12L ECG by the patient himself because of the difficulty of placing the leads.

Solutions capable of detecting AMI using different alternatives to the 12L ECG are also known. For example, heartview P12 of Aerotel (Aerotel Medical Systems of Israel Huo Long), smartheart of SHL (SHL Telemericine of Israel Tegav), and cardioBip (e.g., U.S. Pat. No. 7647093). All of these solutions have significant drawbacks. For example, all of these solutions typically require complex measurement procedures (such as for Heartview, smartheart), and may require a recording procedure by means of a cable attached electrode, removing the garment upward from the waist, using a belt, and multiple steps (see for example US20120059271A1 by Amitai et al). Existing or proposed systems may also require extensive calibration procedures (e.g., cardiobp) that require the patient to enter a medical facility with specially trained personnel before using the device by himself. Finally, all of these procedures may require medical personnel to interpret the recorded ECG.

For example, the Cardiobip device is the simplest device for patient use and it allows for simple positioning of the device and recording of ECG by placing the device against the chest (without a cable or belt). In this example, the diagnostic center can use a PC computer with corresponding software to process the three specific ECG leads and reconstruct the three leads into a standard 12-lead ECG. Reconstruction is required for interpretation of the ECG by medical personnel. The accuracy of reconstructing 12 standard ECG leads using recordings of three specific leads can be achieved by strictly determining the arrangement of integrated electrodes in the mobile device and the corresponding leads. The handheld device may include 5 built-in electrodes (see e.g. EP 1659936), three of which may be placed in contact with the chest of the patient, and the remaining two electrodes in contact with the right and left fingers. The precondition for the reconstruction algorithm in Cardiobip devices is that the diffuse electrical activity of the myocardium is assumed to be approximated by a time-varying dipole (cardiac dipole) immersed in a low-conductivity environment. The cardiac dipole is represented by a vector defined by three non-coplanar projections, so that it can be determined on the basis of potential recordings between any three pairs of points corresponding to three non-coplanar directions (i.e. three specific ECG leads not lying on the same plane). The standard ECG leads are reconstructed as a linear combination of the recorded specific leads and the coefficients defining the transformation matrix. Through extensive analysis it can be shown that there are two main sources of error in such reconstruction. Unfortunately, the heart dipole is only the first term in the multipole mathematical expansion that spreads the heart's electrical activity, and this approximation is valid only for recording points that are at a sufficient distance from the heart. At points close to the heart, the linearity of the system necessary for signal reconstruction is significantly affected by the non-dipole content due to the presence of higher order terms in the multipole expansion.

Furthermore, the described reconstruction techniques for converting several leads into 12-lead signals for analysis by cardiologists or other technical specialists are also limited. In order to carry sufficient diagnostic information, three particular leads need to be as close to orthogonal as possible (e.g., three vector axes with an angle of 90 degrees between each of the three vector axes). Contrary to the orthogonality is the case of three co-planar vectors, i.e. three vectors in the same plane, in which case the diagnostic information corresponding to the axis perpendicular to this plane is completely lost. Importantly, the assumptions required for this modeling (regarding the heart as dipole (and estimating at a distance) and making orthogonal measurements of the heart leads) are contradictory, since it is much easier to obtain orthogonal lead positions if the electrodes are closer to the heart, in which case the non-dipole content is higher. Existing systems (such as cardiobs) must rely on using a configuration that best meets both requirements, with all three leads using the right hand electrode as a reference. These systems have other drawbacks as well. For example, cardiostrip uses three integrated electrodes on the chest side of the device. In clinical studies using Cardiobip, it was observed that the strong pectoral muscle of female and male patients may prevent all three electrodes from being reliably contacted simultaneously with the chest surface. It has also been observed that the symmetrical arrangement of the finger electrodes on the front side of the device may result in a left and right finger exchange in about 10% of the recordings, which makes the recordings useless for diagnosis.

Similarly, other solutions using reduced sets of three leads (e.g., US20140163349A1; US 20100076331) typically use three leads that are coplanar, and thus lack sufficient diagnostic information for AMI detection.

Furthermore, the need for trained medical personnel to interpret recorded ECGs can be an organized challenge and increase the running cost of the system, and the accuracy of human ECG interpretation can vary greatly. Automated software for ECG interpretation is also used in systems for early diagnosis of AMI, but its performance is lower than that of human interpreters. Chest pain is a major symptom suggesting AMI or ischemia (underlying physiological processes). The main ECG parameter used is ST elevation (STE). Unfortunately, a large number of patients presenting with chest pain (up to 15%) have STE (NISTE) of non-ischemic etiology on their ECG presented (to the emergency room). Thus, both the human reader and the automated software may often misinterpret the nist as a new STE due to ischemia. In a typical Emergency Room (ER) scenario, a patient with chest pain is examined by an emergency doctor who must rely solely on-site (current) ECG recordings to decide in time whether or not acute ischemia is present.

It would therefore be advantageous to provide a technique that is capable of separating a new STE from an old STE, as it can significantly increase the performance of automated AMI detection and make it possible to enhance or even replace human interpretation (especially when a qualified human interpretation is not available). Methods and apparatus are described herein that address the problems and needs discussed above, particularly the need for early automatic remote diagnostics of AMI. In particular, the methods and apparatus described herein may provide mechanically stable, long-term, and improved electrical contact while eliminating errors associated with finger contact exchange. In addition, aspects of more frequent or continuous monitoring are addressed.

Summary of the disclosure

Generally, described herein are methods and apparatus for recording and analyzing cardiac signals to automatically detect one or more indicators of cardiac dysfunction, including AMI in particular. These devices may generally include a housing having at least four electrodes arranged in an asymmetric manner on two or more surfaces on the housing to provide orthogonal or quasi-orthogonal leads.

As used herein, a cardiac signal may refer to a voltage generated by a human heart that is sensed between selected points on a surface of a subject's body, and may also be referred to as a cardiac electrical signal (e.g., an electrocardiograph signal). These cardiac signals may include Electrocardiogram (ECG) signals. It should be understood that while the term ECG (electrocardiogram) is generally used to refer to conventional 12-lead ECG signals, the cardiac signals (cardiac electrical signals) described herein are not limited to these conventional 12-lead ECG signals. Further, while the disclosure herein may use and refer to terms including feature points (such as P, Q, R, S, T) and intervals (such as ST segments) on the described cardiac signals, these feature points may correspond to points, locations or areas of location on a conventional 12-lead ECG signal.

Described herein are mobile, handheld devices for automated cardiac electrical signal analysis. For example, an apparatus may comprise: a housing having a back, a first side, and a front; a first electrode and a second electrode integrated on the back of the housing configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode configured to measure a bioelectrical signal from a right hand of the patient; a fourth electrode configured to measure a bioelectric signal from a left hand of the patient; wherein one or both of the third electrode and the fourth electrode are integrated on the front portion of the housing; and a processor within the housing configured to record three orthogonal cardiac leads from the first electrode, the second electrode, the third electrode, and the fourth electrode, wherein fewer than three pairs of the electrodes include the third electrode.

Alternatively or additionally, any of these means may comprise: a housing having a back, a first side, and a front; a first electrode and a second electrode integrated on the back of the housing configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode configured to measure a bioelectrical signal from a right hand of the patient; a fourth electrode configured to measure a bioelectric signal from a left hand of the patient; and a processor configured to record the 3 orthogonal cardiac leads from the first electrode, the second electrode, the third electrode, and the fourth electrode, wherein the processor includes a register configured to store a first set of the three orthogonal cardiac leads taken at a first time and a comparator configured to determine a difference signal between the first set of the three orthogonal cardiac leads and a second set of the three orthogonal cardiac leads taken at a second time.

For example, described herein are mobile, hand-held, three-lead devices for automated electrical cardiac signal analysis. The apparatus may include: a housing having a back, a first side, and a front, wherein the front is parallel to the back; a first electrode and a second electrode integrated on the back of the housing configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode configured to measure a bioelectrical signal from a right hand of the patient; a fourth electrode configured to measure a bioelectric signal from a left hand of the patient; wherein one or both of the third electrode and the fourth electrode are integrated on the front portion of the housing; a processing network (e.g., a resistive network, an operational amplifier summing network, etc.) connecting at least two of the first electrode, the second electrode, the third electrode, and the fourth electrode, wherein the processing network forms a Center Point (CP); a processor within the housing, the processor configured to record 3 orthogonal or quasi-orthogonal cardiac leads from the first electrode, the second electrode, the third electrode, and the fourth electrode, wherein fewer than three pairs of the electrodes include the third electrode; and a communication circuit within the housing configured to send the 3 cardiac leads to an internal or remote processor.

At least one lead may be formed between one of the electrodes and a Center Point (CP) formed by interconnecting at least two electrodes by a resistive network. For example, the third and fourth (left-hand and right-hand) electrodes may be separated by a processing network to form a center point such that at least one lead including the third electrode and the fourth electrode may be measured between the center point and the third electrode or the fourth electrode.

Generally, the device may be oriented relative to the patient's body, including, for example, up and down. The device may include a marker (e.g., one or more of an alphanumeric marker (e.g., a tag), a body shape, light (e.g., an LED), etc.). For example, the device may include a marker on the housing that indicates the orientation of the housing, such as an LED marker on the housing that indicates the orientation of the housing.

The third and fourth electrodes may be disposed on opposite sides with respect to a longitudinal plane of symmetry of the device housing, the plane of symmetry being substantially perpendicular to the back surface of the device housing.

In any of these variations, the ground electrode may be presented on the housing for contacting one hand of the patient, the ground electrode being disposed on a side or front of the housing.

The third electrode or the fourth electrode may be strip-shaped and provided along a side of the device housing.

The housing may comprise a mobile phone housing whereby the third electrode or the fourth electrode is configured as a conductive transparent area on the touch screen of the mobile phone. The housing may be contained in a mobile phone housing. The housing may be an extended structure of a mobile phone housing that communicates with the phone using an electrical connector or wireless communication. The housing may form a mobile phone protective enclosure. For example, the housing may form a mobile phone protective casing with a phone display protective cover, and the third electrode and the fourth electrode are contained in the phone display protective cover.

In some variations, the device is integrated with or connected to a cover (e.g., back cover) of the mobile phone. For example, the housing of the device may be a back cover of a mobile phone, which may be retrofitted to (e.g., used to replace) a standard back cover of a smart phone or other mobile phone. In some variations, the device may be connected to a cover (e.g., back cover) of the mobile phone, for example, by an adhesive or other attachment mechanism.

Also described herein are methods of detecting heart abnormalities, such as detecting ischemia, atrial fibrillation, or other heart disorders; these methods may be automated methods. Any of these methods may be a method for automatic cardiac diagnosis, and may include: acquiring a first set of at least three orthogonal leads from the chest and hands of a patient at a first time; acquiring a second set of at least three orthogonal leads from the chest and hands of the patient at a second time; performing, in the processor, heartbeat alignment of the first set of at least three orthogonal leads and the second set of at least three orthogonal leads to synchronize representative heartbeats of the at least three orthogonal leads from the first set and representative heartbeats of the at least three orthogonal leads from the second set; calculating a difference signal representative of a change between the first at least three orthogonal leads and the second at least three orthogonal leads; detecting a cardiac change indicative of a cardiac condition by comparing a parameter of the first at least three orthogonal leads with a parameter of the second at least three orthogonal leads, or by comparing a parameter of the difference signal with a predefined threshold; and communicating the heart change from the device to the patient.

Alternatively or additionally, a method for automatic cardiac diagnosis may comprise: positioning a device against a chest of a subject at a first recording location, the device configured to detect at least three orthogonal leads from the chest and hands of a patient; acquiring a first set of at least three orthogonal leads from a device at a first time; communicating the first set of at least three orthogonal leads to a processor; positioning the device against the chest of the subject in a second recording position; acquiring a second set of at least three orthogonal leads from the patient at a second time using the device; communicating the second set of at least three orthogonal leads to the processor; performing, in the processor, a heartbeat alignment to synchronize a representative heartbeat from the first set of at least three orthogonal leads with a representative heartbeat from the second set of at least three orthogonal leads; calculating a difference signal representative of a change between the first set of at least three orthogonal leads and the second set of at least three orthogonal leads; detecting a cardiac change indicative of a cardiac disorder by comparing one or more parameters of the difference signal to a predefined threshold; and communicating the heart change from the device to the patient.

For example, a method for automatic cardiac diagnostics may include: placing a device comprising a housing with four integrated electrodes arranged to measure three orthogonal leads from the chest and hands of a patient against the chest of a subject at a first recording position; acquiring a first 3-lead cardiac record (also referred to as a three-lead cardiac record and a three-lead electrical cardiac reading) from the device at a first time (e.g., taking a baseline record (baseline recording)); communicating the first 3-lead record to a processor; holding the device in the same first recording position or placing the device against the chest of the subject in a second recording position; acquiring a second 3-lead record (diagnostic record) from the device at a second time; communicating a second 3-lead record to the processor; performing, in the processor, a heartbeat alignment to synchronize a representative heartbeat from the first 3-lead record with a representative heartbeat from the second 3-lead record; calculating a difference signal representing a change between the first 3 cardiac lead recording and the second 3 cardiac lead recording; detecting a change in a cardiac signal indicative of a cardiac condition (such as ischemia or atrial fibrillation) (e.g., a change in a cardiac signal record, also referred to herein as a cardiac change) by comparing a parameter of a first 3-lead cardiac record to a parameter of a second 3-lead cardiac record, or by comparing a parameter of a difference signal to a predefined threshold; and communicating any cardiac change indicative of the cardiac condition from the device to the patient.

The first recording position and the second recording position may be different or the same. In some variations, the method (or apparatus performing the method) may detect whether the location has changed and either correct a different recorded location or indicate that a more accurate repositioning of the handheld device is required. For example, the method may include compensating for chest electrode misalignment between the first recording position and the second recording position in the processor by compensating for an electrocardiographic axis deviation in the 3-heart lead vector space.

Communicating the first 3-lead electrical cardiac record to the processor may include: the first 3-lead electrical cardiac record is sent wirelessly to a remote processor, part of the cardiac record processing results are sent to a remote process, or only the 3-lead cardiac record is transmitted to an internal processor for processing or for patient alerting.

Generally, these methods may include: preprocessing the first 3-lead electrical cardiac record and the second 3-lead electrical cardiac record in a processor to achieve one or more of: eliminating power line interference, baseline wander, and/or muscle noise; obtaining a representative heartbeat using a fiducial point (fiducials) and median heartbeat procedure; and checking the exchange of the left finger and the right finger.

The parameters of the diagnostic record, the parameters of the reference record and the parameters of the difference signal may be vector magnitudes of the cardiac signal, wherein the vector components are the diagnostic signal at a single instant (J point, j+80 ms), the average of the three cardiac leads of the reference signal and the difference signal or at a predetermined time interval (e.g., ST segment or other predetermined interval) and the radius of a sphere surrounding the vector signal vector end curve of the ST segment (or other predetermined interval).

Where it is desired to detect atrial fibrillation or atrial flutter, the parameters of the diagnostic record, the parameters of the reference record and the parameters of the difference signal may be RR variability (or equivalent), the amplitude of the P-wave (or equivalent), or the average amplitude of the P-wave.

Any of these methods may further comprise transmitting any cardiac signal changes indicative of a cardiac condition from the processor to the device. The method may further include communicating any cardiac signal changes indicative of cardiac symptoms from the device to the patient, including: a visual and/or audible alert is presented to the patient.

For example, a method for automatic cardiac diagnostics may include: placing a device comprising a housing with four integrated electrodes arranged to measure three orthogonal or quasi-orthogonal leads from the chest and hands of a patient against the chest of a subject at a first recording position; acquiring a first 3-lead cardiac record from the device at a first time; communicating the first 3-lead cardiac record to a processor; storing the first 3-lead cardiac record as a reference record; holding the device in the same first position, or placing the device against the chest of the subject in a second recording position; acquiring a second 3-lead cardiac record from the device at a second time; communicating a second 3-lead cardiac record to the processor; preprocessing the first 3-lead cardiac record and the second 3-lead cardiac record in a processor to eliminate power line interference, baseline wander, and muscle noise, using fiducial points and median heartbeat procedures to obtain representative heartbeats, and checking for exchanges of left and right fingers; performing, in the processor, a heartbeat alignment such that a representative heartbeat from the first 3-lead cardiac recording and a representative heartbeat from the second 3-lead cardiac recording are in the same time period such that corresponding points are synchronized; compensating in the processor for chest electrode misalignment between the first recording position and the second recording position by compensating for an electrocardiographic axis deviation in the 3 cardiac lead vector space; calculating a difference signal representing a change between the first 3 cardiac lead recording and the second 3 cardiac lead recording; detecting a change in the cardiac signal indicative of a cardiac condition (e.g., ischemia, atrial fibrillation, atrial flutter, etc.) by comparing a parameter of the first 3-lead cardiac record to a parameter of the second 3-lead cardiac record, or by comparing a parameter of the difference signal to a predefined threshold; any heart signal changes indicative of a heart condition are communicated from the device to the patient.

Generally, described herein are apparatuses configured to perform any of the methods described herein. For example, an apparatus configured to provide automatic cardiac diagnostics may include: a housing including at least four electrodes connected to a processor within the housing; wherein the processor is configured to: acquiring a first set of at least three orthogonal leads from the chest and hands of a patient at a first time; acquiring a second set of at least three orthogonal leads from the chest and hands of the patient at a second time; performing heartbeat alignment on the at least three orthogonal leads of the first set and the at least three orthogonal leads of the second set to synchronize representative heartbeats of the at least three orthogonal leads from the first set and representative heartbeats of the at least three orthogonal leads from the second set; calculating a difference signal representative of a change between the first at least three orthogonal leads and the second at least three orthogonal leads; detecting a cardiac change indicative of a cardiac condition by comparing a parameter of the first at least three orthogonal leads with a parameter of the second at least three orthogonal leads, or by comparing a parameter of the difference signal with a predefined threshold; and communicating the heart change from the device to the patient.

While the description of the methods and apparatus included herein describes the use of a set of orthogonal or quasi-orthogonal cardiac signals, the methods and apparatus may be used with any set of signals (cardiac electrical signals) that contain significant independent cardiac information. For example, embodiments using cardiac leads represented by vectors that are not perfectly orthogonal do not depart from the spirit of the invention. It is important that the individual heart vectors be oriented at a relative angle of more than 30 ° with respect to each other. Such a small relative angle may still provide significantly linearly independent information and allow the devices and methods described herein to produce similar and clinically/diagnostically relevant results. Thus, for simplicity, without implying any limitation, we may refer to our cardiac leads herein as orthogonal leads. Thus, orthogonal leads may be strictly orthogonal (e.g., less than 10 °, less than 8 °, less than 7 °, less than 6 °, less than 5 °, less than 4 °, less than 3 °, less than 2 °, less than 1 °, etc.) or substantially orthogonal (e.g., less than 30 °, less than 25 °, less than 20 °, less than 15 °, etc. from 90 °) from a lead relative angle. Alternatively, quasi-orthogonality may be estimated based on a cross-correlation function of a combination of data from any two leads that need to be at about the same time and with the same device. In view of this, orthogonality in this context refers to the amount of independent information content, if the mutual correlation is less than 0.6, then two leads from a set can be considered quasi-orthogonal.

For example, an adhesive patch apparatus for synthesizing a 12-lead electrocardiogram is described herein. These devices may include: an adhesive material patch having a back side and a front side, wherein the back side is configured to be adhesively secured to a chest of a patient; a first electrode and a second electrode integrated on the back of the patch configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode on the front face of the patch and configured to measure a bioelectric signal from the right hand of the patient; a fourth electrode on the front face of the patch and configured to measure a bioelectric signal from the left hand of the patient; a processing network forming a center point of transfer between the third electrode and the fourth electrode in a sagittal plane through the patient's chest while the housing is held adhesively secured to the patient's chest, wherein three orthogonal cardiac leads are formed by the electrodes and the center point; and a processor located within the housing on the patch configured to process three orthogonal cardiac leads derived from the first electrode, the second electrode, the third electrode, and the fourth electrode.

For example, an adhesive patch device for synthesizing a 12-lead electrocardiogram may include: an adhesive material patch having a back side and a front side, wherein the back side is configured to be adhesively secured to a chest of a patient; a first electrode and a second electrode integrated on the back of the patch configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode on the front face of the patch and configured to measure a bioelectric signal from the right hand of the patient; a fourth electrode on the front face of the patch and configured to measure a bioelectric signal from the left hand of the patient; a processing network forming a center point of transfer between the third electrode and the fourth electrode in a sagittal plane through the patient's chest while the housing is held adhesively secured to the patient's chest, wherein three orthogonal cardiac leads are formed by the electrodes and the center point; and a processor configured to process the three orthogonal cardiac leads, wherein the processor comprises a register configured to store a first set of values of the three orthogonal cardiac leads taken at a first time and a comparator configured to determine a difference signal between the first set of values of the three orthogonal cardiac leads and a second set of values of the three orthogonal cardiac leads taken at a second time.

Any of these devices may include a communication circuit within the housing configured to transmit the processed three orthogonal cardiac leads to a remote processor. The processor may be configured to receive information returned from the remote processor. The device may include a marker on the housing that indicates the orientation of the patch when applied to the chest of the patient. For example, the device may include an LED on the housing that indicates the orientation of the housing.

The third and fourth electrodes may be disposed on opposite sides with respect to a longitudinal plane of symmetry of the housing, the plane of symmetry being substantially perpendicular to the back face of the housing. For example, the housing may extend protruding from the front face of the patch and may include sides (e.g., four sides). In some examples, the device includes a ground electrode (e.g., on the housing) for contacting one hand of the patient, e.g., disposed on a side or front of the housing. The third electrode or the fourth electrode may be strip-shaped and disposed along the first side of the case.

When the detection circuit (e.g., finger detection circuit) detects that both finger electrodes (e.g., third electrode and fourth electrode) are in contact with a finger (e.g., a finger from the left hand of the patient and a finger from the right hand of the patient), any of these devices may be configured to operate (and switch between) different modes of operation, including a 12-lead ECG detection mode. When the detection circuit indicates that neither finger electrode is in contact with a finger, the device may switch to standby mode (or 1-lead ECG mode). In the standby/1-lead ECG mode, the device may be configured to take 1-lead ECG measurements from only the chest electrodes (first and second electrodes); these measurements may be taken on a predetermined schedule (e.g., once a day, twice a day, every other day, etc.), and stored, processed, and/or transmitted. For example, the processor may be configured to automatically detect a 1-lead ECG signal from the first electrode and the second electrode when the detection circuit does not detect finger contact on both the third electrode and the fourth electrode.

Thus, in general, any of these devices may include a detection circuit configured to detect finger contact on one or both of the third and fourth electrodes. In general, the processor may be configured to collect three orthogonal leads when the detection circuit detects finger contact on both the third electrode and the fourth electrode (e.g., in the first mode).

Examples of adhesive patch devices for synthesizing 12-lead electrocardiographs may include: an adhesive material patch having a back side and a front side, wherein the back side is configured to be adhesively secured to a patient's chest; a first electrode and a second electrode integrated on the back of the patch configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode on the front face of the patch and configured to measure a bioelectric signal from the right hand of the patient; a fourth electrode on the front face of the patch and configured to measure a bioelectric signal from the left hand of the patient; a processing network forming a center point of transfer between the third electrode and the fourth electrode in a sagittal plane through the patient's chest while the housing is held adhesively secured to the patient's chest, wherein three orthogonal cardiac leads are formed by the electrodes and the center point; and a processor configured to process the three orthogonal cardiac leads, wherein the processor comprises a processor configured to: the method further includes operating and measuring three orthogonal cardiac leads in a first mode when finger contact is detected on both the third electrode and the fourth electrode, and operating in a standby mode when finger contact is not detected on both the third electrode and the fourth electrode.

Thus, electrocardiogram (ECG) sensing and auditing devices and methods are described herein that may provide multiple single channel acquisitions for detecting arrhythmias that may include a change in QRS axis or a change in QRS width, and/or may distinguish arrhythmias from artifacts. The "gold standard" for assessing heart rhythm abnormalities is a 12-lead ECG or a 12-lead Holter. The advantage of a standard 12-lead ECG is that rhythms, conduction, repolarization can be assessed from multiple leads, allowing diagnosis of heart structural, electrophysiological and metabolic abnormalities, and drug effects.

The peer review publications indicate that the 12-lead Holter monitor detects about 17% more reportable events than the leading ECG patch technique within the first 24 hours of monitoring any of the six arrhythmias (supraventricular tachycardia, AF/AFL, pause >3s, AVB, ventricular tachycardia, or polymorphic ventricular tachycardia/fibrillation). Other arrhythmias and conduction disorders are likely not detected by the ECG patch, possibly because they are single-lead in nature as compared to the 12-lead Holter monitor. Some ECG patches provide multiple electrodes attached only to the chest, but the diagnostic information they provide is still limited to a single signal plane. To achieve 12-lead equivalence in terms of diagnostic content, the patch described herein can record signals on all three human primary axes: frontal, sagittal and transverse axes (X, Y and Z).

Cardiac electrophysiological disorders often coexist with circulatory diseases. Pathophysiological conditions including current or pre-existing ischemia, infarction, left ventricular hypertrophy and hereditary arrhythmias may also be revealed by long term (weeks) monitoring. Patients who are discharged after interventional treatment of coronary artery disease (stent or bypass surgery) need to be monitored to eliminate their doubt and to reduce unnecessary readmission of these patients. The detection of coronary artery disease using a single lead ECG device is unreliable (less accurate) and therefore single lead techniques are disabled for coronary artery disease detection. The methods and apparatus herein address these issues.

While not all occurrences of arrhythmias and other heart diseases are symptomatic, most are symptomatic. The gold standard for diagnosing many rhythm disorders is the correlation of symptoms with ECG. In practice, this means that the patient wearing the ECG patch needs to be somehow marked with a symptomatic event (symptomatic event). Typically, this is accomplished by the patient pressing a special "symptom present" button (see, e.g., fig. 12), typically located on the top surface of the patch. To some extent, this enables event monitoring functionality in the ECG patch. Typically, after the device is removed from the patient's chest, an entire multi-week record is sent for analysis.

For example, described herein is a cardiac monitoring patch device (e.g., an ECG patch for 12-lead detection) comprising: a housing having a front surface and a rear surface; two chest electrodes on the rear surface, the two chest electrodes being separated by about 5cm for most orthogonal signal collection, preferably by 10cm or more; a first finger electrode and a second finger electrode on the front surface; wherein the rear surface comprises an adhesive configured to secure the two chest electrodes in contact with the skin; and a processor configured to detect when a first finger of a first hand contacts the first finger electrode simultaneously with a second finger of a second hand contacts the second finger electrode, and to record electrical signals from the two chest electrodes and the two finger electrodes.

In some examples, the processor may be configured to automatically detect ECG signals (e.g., 1-lead ECG signals) from the first and second electrodes when the detection circuit does not detect finger contact on both the third and fourth electrodes. The processor may also be configured to detect an irregular cardiac signal from the detected ECG, and in some examples, when an irregular cardiac signal is detected, the processor may prompt the patient to touch the third and fourth electrodes, and/or may prompt the patient to activate a "symptom present" control (e.g., a button).

In general, described herein are adhesive patch devices (devices, systems, etc.) for synthesizing 12-lead electrocardiograms using four electrodes (two hand electrodes and two chest electrodes). For example, also described herein is an adhesive patch apparatus for synthesizing a 12-lead electrocardiogram, the apparatus comprising: an adhesive material patch having a back side and a front side, wherein the back side is configured to be adhesively secured to a patient's chest; a first electrode and a second electrode integrated on the back of the patch configured to measure a bioelectric signal from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart; a third electrode on the back of the right arm region of the patch and configured to measure a bioelectric signal from the right arm of the patient; a fourth electrode on the back of the left arm region of the patch and configured to measure bioelectric signals from the left arm of the patient; a processing network forming a center point of transfer between the third electrode and the fourth electrode in a sagittal plane through the patient's chest while the housing is held adhesively secured to the patient's chest, wherein three orthogonal cardiac leads are formed by the electrodes and the center point; and a processor within the housing on the patch configured to process three orthogonal cardiac leads derived from the first electrode, the second electrode, the third electrode, and the fourth electrode. The processor may be configured to periodically process three orthogonal cardiac leads from the first electrode, the second electrode, the third electrode, and the fourth electrode. In some examples, the processor may be configured to continuously process three orthogonal cardiac leads from the first electrode, the second electrode, the third electrode, and the fourth electrode.

Brief Description of Drawings

Fig. 1A shows a variation of a schematic configuration of a diagnostic system for detecting heart disorders such as AMI, which includes a local processor in the system.

FIG. 1B is another schematic diagram of a remote diagnostic system in which the processor is remote from the handheld device.

Fig. 2A shows a front (non-chest) view of a variation of a handheld device having two recording electrodes and one ground electrode.

Fig. 2B shows a rear (chest) view of a variation of a handheld device having two recording electrodes.

Fig. 2C shows an isometric view of the handheld device.

Fig. 2D shows a front view of the device placed against the patient's body at the recording position.

Fig. 3A shows a simple electrical scheme for obtaining a center point CP by connecting the electrodes of both hands via a simple resistive network with two resistors.

Fig. 3B shows an electrical scheme for obtaining a center point CP by averaging electrode signals via a known operational amplifier (op amp) configuration.

Fig. 4A shows a schematic configuration of three cardiac leads measured on the torso, with one lead using the center point as the reference pole—the preferred embodiment.

Fig. 4B shows a circuit with three cardiac leads, wherein one lead uses the center point as the reference pole.

Fig. 4C shows a schematic configuration of three cardiac leads measured on the torso, with two leads using the center point as a reference pole.

Fig. 4D is a circuit with three cardiac leads, wherein two leads use the center point as a reference pole.

Fig. 4E, 4F and 4G show schematic diagrams of three possible configurations for measuring 3 leads between two chest electrodes and two hand electrodes.

Fig. 5A shows a front (non-chest) view of a handheld device having two front electrodes and one side electrode.

Fig. 5B shows a back (chest) view of a handheld device having two front electrodes and one side electrode.

Fig. 5C shows an isometric view of a handheld device having two front electrodes and one side electrode.

Fig. 6A is a front (non-chest) view of a handheld device with electrodes on the edges of the device.

Fig. 6B is a rear (chest) view of the handheld device with electrodes on the edges of the device.

Fig. 6C is an isometric view of a handheld device with electrodes on the edges of the device.

Fig. 7 is an isometric view of a handheld device implemented as a flip cover housing attachable to a mobile phone.

Fig. 8 shows a flow chart of a method for detecting AMI.

Fig. 9 shows an example of a patient with BER (benign early repolarization), showing a median heartbeat of 12 leads. Both pre-dilation and dilation recordings show chest lead ST elevation, which is often problematic for a human reader to distinguish ischemic from non-ischemic recordings.

Fig. 10 is an example of a patient with BER (benign early repolarization) showing the median heartbeat for 3 specific leads. The signal difference between the pre-dilation record and the dilation record enables the algorithm to distinguish between ischemic and non-ischemic records.

Fig. 11 shows one example of a typical ECG patch size and placement: two adhesive chest electrodes were positioned about 10cm apart for single lead ECG recording.

Fig. 12 shows a prior art patch.

Fig. 13 shows an example of a handheld ECG.

Fig. 14 shows one example of a 12-lead Holter ECG monitor.

Fig. 15 shows a bottom view of one example of a view of an adhesive device (e.g., XYZ patch) with adhesive chest electrodes.

Fig. 16 shows a top view of the patch device of fig. 15.

Fig. 17 shows one example of a patch device (e.g., an ECG patch for detecting 12 leads) attached to a patient's chest.

Fig. 18 shows one example of using a patient's finger in an adhesive patch apparatus.

Fig. 19 shows an example of an adhesive patch apparatus attached vertically.

Fig. 20A schematically illustrates an example of a flow chart of an adhesive patch apparatus as described herein.

Fig. 20B schematically illustrates an example of a flow chart of an adhesive patch apparatus including arm contact as described herein.

Fig. 21A-21C illustrate alternative examples of adhesive patch apparatus as described herein.

Detailed Description

Described herein are apparatuses (including devices and systems) and methods for remote diagnosis of cardiac conditions, such as Acute Myocardial Infarction (AMI), atrial fibrillation (AFib), and the like. For example, described herein are hand-held or manually-operated devices having a particular electrode configuration capable of recording three orthogonal cardiac lead signals in an orientation-specific manner and transmitting those signals to a processor (e.g., a PC or other computing device). In particular, described herein are adhesive heart devices that can be worn on the chest of a subject and operated by both hands of the subject for extended periods of time. The processor may be configured to diagnose/detect the AMI and send diagnostic information back to the handheld device and/or to a personal device (such as a cell phone, tablet, etc.) of the patient (or caregiver). The handheld (and/or adhesively worn) device may communicate diagnostic information to the patient via a characteristic sound, voice message, or via a graphical display. The processor may be configured via hardware, software, firmware, etc., and may process the received signals to generate a difference signal and extract information reliably related to the detection of AMI (and additional information of clinical relevance). Thus, these devices and methods can perform automatic detection of cardiac conditions on a 3-lead system basis without the need for a 12L ECG reconstruction, reducing or eliminating the need for medical personnel to interpret ECG, unlike prior art systems which typically rely on medical personnel to make such decisions. The automated diagnostic methods described herein, in combination with the improved cardiac apparatus, address many of the needs and problems that exist in other systems.

In particular, described herein is a 3-lead cardiac recording device for placement on the chest of a user, comprising an electrode arrangement on the front and back (and in some variations on one or more sides) such that the device can be held in a predefined orientation by the user's hands in order to record a 3-lead cardiac signal when held against the chest of the user. To achieve the functionality described above, in some examples, the device (which may be hand-held or adhesive applied/worn) may record three leads without the use of a cable (e.g., may include only surface electrodes that are held or held against the body). Furthermore, the resulting three leads are non-coplanar and as close to orthogonal as possible. In some examples, at least one electrode may be mounted on the front side of the device (opposite the chest side), which may provide a force that helps to hold the device against the chest. Unlike prior art devices, a low non-dipole content is not required, as the apparatus and methods described herein do not require reconstructing a 12L ECG from the 3 measured leads.

The devices described herein are configured to be mechanically stable and allow good electrical contact with the chest and may eliminate the need for hand contact exchange. In some examples, the devices described herein may include five electrodes, e.g., four recording electrodes and one ground electrode. The devices described herein may include two chest electrodes that are recording electrodes and may be located on the back side of the device (e.g., and in some examples, may be adhesively coupled to the skin). In some examples, the remaining non-chest electrodes may be used to collect cardiac signals from fingers of the right hand and fingers of the left hand; in some examples, a third non-chest electrode may be used as the ground electrode. At least one of the three non-chest electrodes may be mounted on the front side for finger compression. In some examples, this may create sufficient force to hold the device against the chest. In some variations, the electrodes may be asymmetrically arranged; this asymmetric electrode configuration may prevent the need to identify which finger/hand is being used. For example, one of the three non-chest electrodes may establish contact with one finger of the first hand, and the remaining two electrodes may establish contact with the other hand. One of the two electrodes may be used as a common ground electrode and the other may be used for signal measurement. An example of such a configuration has two chest recording electrodes, one recording finger electrode on the left side of the device, and two finger electrodes, one recording and one ground electrode, on the front side of the device. In some examples, the optimal location of the device on the chest may be to center the device on the left side of the chest approximately above the center of the heart muscle. In this position, the chest electrode may be located approximately on the midline of the clavicle (i.e., a vertical line passing through the midpoint of the clavicle), identical to the V4 electrode of a conventional ECG, and the lower chest electrode is approximately at the level of the lower end of the sternum.

In another embodiment, the ground electrode may be eliminated from the configuration, and if a signal amplifier configuration without ground is used, acceptable 50-60Hz electrical noise performance may be provided. The four recording electrode configuration (having two chest electrodes and two finger electrodes) can also satisfy the above-described condition of high orthogonality. The simplest way to meet this requirement is to record the signal in three main body directions: transverse (left arm-right arm), sagittal (posterior-anterior), and caudal (caldial) (cephalad-toe). For example, a signal in the lateral direction can be obtained by measuring a lead between the left and right hands. The signal in the caudal direction may be obtained by measuring a lead between two chest electrodes, with the proviso that the distance between the chest electrodes in the caudal direction is at least about 5cm, in some examples greater than about 10cm, so as to be greater than the approximate diameter of the heart muscle. In an ideal case, the sagittal signal would be measured between the back and chest of the patient, which is not possible with the limitation of using only finger and chest electrodes. To overcome this problem we use a simple resistor network to make a Center Point (CP) close to the electrical center of the heart. To record the leads in the general sagittal direction, we recorded the voltage of the lower chest electrode relative to the Center Point (CP) obtained using two hand electrodes and two resistors. The two resistors may be equal (each about 5k omega) or unequal (the first resistor between the left hand electrode and CP is about 5k omega and the second resistor between the right hand electrode and CP is about 10k omega). This asymmetry reflects the left position of the heart in the torso, moving the CP to the approximate electrical center of the heart. In this way we obtain a substantially orthogonal three-lead system.

Other similar lead configurations with the same CP can be selected using the same set of two chest electrodes and two hand electrodes, wherein the distance between the chest electrodes in the tail direction is at least 5cm, preferably greater than about 10cm. Such a lead configuration may be substantially orthogonal, for example, when two chest electrodes are used to record the leads using a reference pole at CP. Another possible way of defining CP is to use three electrodes (two hand electrodes and one chest electrode) and 3 resistors connected in a Y (star) configuration.

Other lead configurations without CP may also be used, as may configurations that record signals of two chest electrodes and a right hand electrode relative to a left hand electrode. This configuration without resistors or CP has a higher immunity to electrical noise, e.g., 50-60Hz, but has a worse orthogonal lead direction than the described configuration using CP. In general, any other lead configuration using the same four described electrodes (20 configurations without CP in total) results in non-coplanar leads, and as such diagnostic signals are captured in all three directions, but may lack a high degree of orthogonality. However, these configurations may have different levels of orthogonality depending on the use of the right hand electrode. The configuration using the right hand electrode as a common reference point among all 3 leads may have the lowest orthogonality because the right hand electrode is the farthest from the heart among the four electrodes, and thus the angle between vectors corresponding to the three leads is the smallest. The configuration using the right hand electrode in two leads has better orthogonality, while the best orthogonality is achieved in a configuration using the right hand electrode in only one lead.

If one or more chest electrodes are added on the back side of the device and one or more corresponding additional leads are recorded and used in the diagnostic algorithm, the effectiveness of the described solution is not affected. In addition, if the palm or any other part of the hand is used instead of the finger to press the front electrode, the effectiveness is not affected.

In order to prevent the device from being flipped over during the recording procedure so that the upper side faces the patient's toes rather than his head (which would lead to useless recordings), the upper or front side of the device can be clearly identified and/or formed (including marked) so as to be easily distinguishable by the patient, for example by means of an LED diode indicating the current recording phase.

In some examples, the cardiac device (including a handheld or adhesive device configuration) may be configured as a standalone device comprising: an ECG recording module including an amplifier and an AD converter, a data storage module, a communication module operating in GSM, WWAN, or similar telecommunications standards for communicating with a remote processor (e.g., PC computer, tablet, smart phone, etc.), and circuitry (e.g., wi-Fi, bluetooth, etc.) for communicating diagnostic information to a user. Alternatively, the heart device may be implemented as a modified mobile phone comprising the measuring electrodes and the recording module. Furthermore, the heart device may be implemented as a device that is attached to the mobile phone as a housing or interchangeable back cover. The attached device contains the measurement electrode and recording module and communicates with the mobile phone using a connector or wireless connection, such as bluetooth or ANT.

The hand electrode may be mounted on the display side of the mobile phone if the device is configured as a modified mobile phone or as a device attached to a mobile phone. The hand electrodes may be integrated in the edge of the display side of the phone or as conductive areas contained in a transparent layer covering the display of the phone arranged in the same way as the hand electrodes in the preferred embodiment and marked with a specific color when the heart signal measurement application is activated.

The signal processing and diagnostic software may also run on a processor (e.g., a microprocessor), including a processor integrated in the device, rather than on a remote processor (e.g., a PC computer). In such a case, it may no longer be necessary to communicate the recorded information to a remote computer other than the data and process backup. Further, when the diagnostic process is performed by a remote processor, a backup version of the software running on the microprocessor may be integrated in the device and used when the user is in an area that is not covered by the wireless network.

Methods and devices for automatically detecting AMI (or ischemia, underlying physiological process) are also described herein. These automated systems may include three cardiac leads that are substantially orthogonal, containing most of the diagnostic information present in a conventional 12-lead ECG. Each user may be registered in the diagnostic system by performing a first transmission of his/her asymptomatic cardiac recordings with 3 cardiac leads. This first record may be used as a reference baseline record for AMI detection in a diagnostic record (diagnostic record means any further record of 3 cardiac leads of the same user). The availability of reference baseline cardiac recordings may allow distinguishing new STEs (or equivalent parameters) from old STEs (or equivalent parameters) and also distinguishing other cardiac signal changes that suggest AMI, providing a tool for automated AMI detection that may be comparable to a human ECG interpreter.

The optimal placement of the devices described herein (e.g., handheld and/or adhesive) that may be generally on the chest is to center the device on the left side of the chest, generally above the center of the heart muscle. In this position, the right edge of the device may be about 3cm from the midline of the sternum (the vertical midline of the sternum), and the lower edge of the device is approximately at the level of the lower end of the sternum. In an ideal case, the user selects the best position on the chest in the first fiducial recording and repeats this position in each subsequent diagnostic recording. In this case, the cardiac recording is repeatable and changes in the cardiac signal indicative of AMI are readily detected.

In some variations, an adhesive may be used to secure the device to the chest of a subject (e.g., of a patient), including over an extended period of time (such as days, weeks, or months). Thus, the device may include an adhesive material, or an adhesive patch or pad (dock) may be used to attach to the device reproducibly and hold it in a predetermined position by the user. For example, a self-adhesive patch with a chest electrode (connected to a device with a chest electrode) may be used to achieve that the electrodes are in the same recording position during the reference recording and any further test recording. A self-adhesive patch with chest electrodes may be attached for the first registration and held in the same position on the user's chest. Similarly, patches may be used that the device may dock to place the electrodes in predetermined locations. The user needs to touch the hand electrode.

In a real-world situation, the user may place the device in a different location than the reference location, which may jeopardize the diagnostic accuracy. This misalignment corresponds to a virtual change of the electrocardiographic axis in the 3D vector space defined by the 3 cardiac leads. In some variations, this angular change may be calculated for each test record compared to the reference record. If the angular change is greater than a threshold (such as 15 degrees), the user may be prompted to select a position closer to the reference position. If the variation is below the threshold value, it is possible to compensate by rotating the signal loop of the test record in the 3D vector space and obtain a signal substantially equivalent to the reference signal.

Although exchange of left and right fingers or inverting the device is not possible (due to asymmetric electrode configurations and arrangement of the device, e.g. by clearly marking on the upper or front side of the device), it is still possible. In this case, all three signals may become unavailable. Both user errors can be easily detected, since in both cases the lead signal recorded between the left hand and the right hand can become inverted. In this case, the user can be reminded to repeat recording using the correct recording position.

In some variations, the method for automatically detecting AMI (or ischemia) may be the following steps: placing the device in a recording position on the chest of the user; acquire a first 3-lead cardiac record and communicate a signal to a processing unit; storing the first record as a reference record in a database of the processing unit for further comparison with any subsequent diagnostic records; a 3-lead cardiac diagnostic record is acquired and signals are communicated to a processing unit and the resulting signals are processed. Processing the stored reference signal and the diagnostic recorded signal by the processing unit may comprise the steps of: preprocessing to eliminate power line interference, baseline drift, and muscle noise, using fiducial and median heartbeat procedures to obtain representative heartbeats, checking for exchanges of left and right fingers, aligning heartbeats to synchronize the representative heartbeats of the fiducial and test recordings in the same time period for corresponding points, compensating for misalignment of chest electrodes in the recorded test signal by compensating for heart axis deviations in the 3 heart lead vector space, calculating a difference signal (which represents changes between the fiducial and diagnostic 3 heart lead signals), detecting heart signal changes indicative of ischemia by comparing parameters of the test recordings to parameters of the fiducial recordings, or by comparing parameters of the difference signal to predefined thresholds, communicating information to the device by the processing unit, and ultimately communicating diagnostic information to the patient by the device.

In the case of ischemia, STE (ST elevation) is the most common ECG change, often measured at the J point or at most 80 milliseconds later. Using STE as a parameter, by comparing STE in the test record with the reference record, changes in ischemia can be detected. Furthermore, by measuring the vector difference (STVD) of the ST vector in the vector space defined by the 3 specific cardiac leads, using the fiducial recording as a reference, a change in ischemia can be detected. As described above, while these parameters (e.g., ST, J, STVD, STE) are defined with reference to a conventional 12-lead ECG signal, they refer herein to equivalent metrics determined for the three cardiac leads (orthogonal signals) described herein. Thus, these equivalent points, regions, or phenomena (e.g., STE, ST, J, STVD, etc.) can be identified by a comparison between the cardiac signal described herein and a conventional ECG signal (including a conventional 12-lead ECG signal).

Other parameters of the ECG signal may also be used for comparison with the base reference signal, such as "Clew", which is defined as the radius of the sphere surrounding the vector signal vector end curve between the J and j+80 millisecond points.

The individual heart signal is highly repeatable in terms of its shape. The change in signal shape is typically small for healthy, or otherwise stable individuals. For example, a change in the position of the heart relative to the chest cavity may change the electrocardiograph axis by up to 10 °. However, when the signal shape can change over a period of time, there are conditions such as Benign Early Repolarization (BER). Such signal variations are highly independent and may be significant. To compensate for this variation, multiple fiducial recordings taken by the user over a period of time may be used to form a reference that forms a 3D contour in the vector space defined by the 3 particular cardiac leads (rather than a single point when a single fiducial recording is used). When such a 3D contour reference is used, the ST vector difference (STVD) may be defined as a distance from the 3D contour instead of a distance from the base ST vector. If more than one parameter is used for ischemia detection, such a reference profile may be constructed as a hypersurface (hypersurface) in a multidimensional parameter space defined by such parameters. In this case, a hyper-distance (hyper-distance) from the reference hypersurface will be defined in the parameter space.

In some cases, the change in signal shape may also be intermittent (the condition "getting around"), such as Brugada syndrome, WPW syndrome, bundle Branch Block (BBB), etc. To compensate for signal variations under such conditions, two sets of fiducial recordings (e.g., at least two recordings) may be used to define a reference, one with a normal signal and one with the intermittent condition present. These two groups will form two 3D contours in vector space, which form a reference for comparison. The two 3D contours may or may not overlap. If there is no overlap, then the ST vector difference (STVD) will be defined as the distance from the closest point on the two 3D contours. If more than one parameter is used for ischemia detection, such a reference profile will be constructed as two hypersurfaces in the multidimensional parameter space defined by such parameters. In this case, the hyper-distance from the reference hypersurface will be defined in the parameter space.

The main use of the methods described herein may be applied to detect the most urgent cardiac diagnosis, AMI. In addition, diagnostic methods (e.g., software) in a remote processor (or an integrated processor in a handheld device) may detect other cardiac conditions, such as chronic Coronary Artery Disease (CAD), left Ventricular Hypertrophy (LVH), bundle Branch Block (BBB), bragg syndrome, rhythm disorders such as Atrial Fibrillation (AF), and the like.

Although the methods described herein do not require reconstruction of a conventional 12-lead ECG recording, the methods described herein can be used to reconstruct a conventional 12-lead ECG recording. Among many of the disorders to be detected mentioned above, although to a lesser extent than AMI, treatment may be urgently needed. Furthermore, many of such conditions are transient and may be detected using the techniques described herein, but may not exist when the user later arrives at the doctor's office. In this case, it would be useful to present an ECG signal of the condition found at the time of recording so that the doctor can use it to confirm the diagnosis. The physician is familiar with conventional 12-lead ECG recordings. Thus, the 3 specific cardiac leads recorded at the time of the condition discovery can be converted to produce an approximate reconstruction of a conventional 12-lead ECG recording. Such a reconstruction may be obtained by multiplying 3 specific cardiac leads with a 12 x 3 matrix. The matrix may be obtained as a population matrix (population matrix), i.e. a matrix with coefficients calculated as the mean (or median) of individual matrices obtained by simultaneously recording a regular 12-lead ECG of a group of individuals and 3 specific cardiac leads, wherein each individual matrix is obtained using a least squares method. The coefficients of such a matrix depend on the shape of the user's body. Thus, rather than using a single population matrix, multiple matrices may be used, each for a group of users defined according to simple parameters of body shape and structure (e.g., gender, height, weight, chest circumference, etc.) that are readily available to the user. Furthermore, matrix coefficients may be obtained as a continuous function of such body parameters.

Fig. 1A shows a variant of a method of operating a system 2 for cardiac signal detection and/or diagnosis. In fig. 1A, a user may record a cardiac signal (e.g., two or more times), and the device may process three orthogonal leads to compare different times (e.g., reference versus measured time). The processor of the device may also determine whether the resulting difference signal is indicative of a cardiac problem and may alert the user. The user (patient) may then obtain medical assistance as desired. Fig. 1B shows a view of another variant of a system and method for detecting cardiac dysfunction, comprising a system 1 for remote diagnosis of AMI, comprising a handheld device 2 and a PC computer 4 connected to the device via a telecommunication link, the handheld device 2 containing built-in electrodes for cardiac signal acquisition, the built-in electrodes being mounted directly on a housing 3 of the handheld device.

The apparatus further comprises: a cardiac signal recording circuit including an amplifier and an AD converter for amplifying the signals detected by the electrodes, a data memory (e.g., memory) for storing the recorded signals, a communication circuit operating in a GSM, WWAN or similar telecommunications standard for communicating with the remote processor 4, and a visual device and/or audio device (e.g., monitor, speaker, etc.) for communicating diagnostic information to a user.

The device may communicate with a remote processor 4 via an integrated communication circuit. The remote processor 4 may communicate with the handheld device 2 via an integrated communication module. The processor 4 may be provided with diagnostic software for processing the received cardiac signals, generating diagnostic information and for sending information back to the handheld device for communicating the diagnostic information to the patient in the form of graphical information via a microphone generating characteristic sound or voice messages or via a display integrated in the device. Thus, the system may have the ability to perform automatic detection of heart conditions on the basis of a 3-lead system and without the need for interpretation of the processed diagnostic information by an expert. Alternatively, instead of a remote processor, the system may comprise a microprocessor integrated in the housing 3 of the handheld device for processing the recorded cardiac signals and generating diagnostic information.

Fig. 2A, 2B and 2C show front, rear and isometric views, respectively, of an example of a handheld device. Fig. 2A shows a front view of the device 2 fixed in a recording position by a user. The housing 3 of the device may contain four recording electrodes A, B, C, D and one ground electrode G arranged such that this arrangement is capable of recording three specific ECG lead signals. On the flat back surface 5 of the device in this example two recording electrodes (a and B) are mounted for contact with the chest of the patient at the recording position. The two chest electrodes (a and B) are preferably arranged to cover a distance of more than at least 5cm, preferably more than about 10cm in the caudal direction. The reason for having such a spaced arrangement is to achieve a distance greater than the approximate diameter of the heart muscle, which is required to be as close as possible to the lead orthogonality.

In addition to the two chest electrodes (a and B), the device in this example has two recording electrodes (C and D) mounted on a flat front surface 6, the front surface 6 being substantially parallel and opposite to the back surface 5. These electrodes (C and D) are used to record the cardiac signal of the hand by pressing with the fingers of the left and right hand, respectively. The fifth electrode G serves as a ground electrode and is mounted on the front surface 6 for pressing with a left hand finger.

Referring back to fig. 2A, a view of the preferred embodiment of the present invention is shown in the recording position. To operate, a user (e.g., a patient) places the device in his left hand such that the patient's index and middle fingers contact electrodes C and G, respectively, positions the device and presses the device against his chest such that chest electrodes a and B contact his chest in the manner shown in fig. 2E for producing intimate contact between the chest and the device. This may create enough pressure to hold the device against the chest. At the same time, the finger of the right hand (or any other part of the right hand) presses against a reference electrode D mounted on the front surface 6 of the housing 3.

Referring back to fig. 2D, a front view of the apparatus placed against the patient's body in the recording position is shown in accordance with a preferred embodiment of the present invention. In the optimal recording position, the center of the device is placed closely above the center of the heart such that chest electrodes a and B are located approximately on the midline of the clavicle (a vertical line passing through the midpoint of the clavicle) and the lower chest electrode B is approximately at the level of the lower end of the sternum.

The example in fig. 3A shows a simple electrical scheme to obtain the center point CP by connecting the electrodes of both hands via a simple resistive network with two resistors. Similarly, fig. 3B shows an electrical scheme for obtaining the center point CP using buffering and averaging via an operational amplifier.

Fig. 4A shows a spatial view of a lead configuration showing the arrangement of the active electrodes A, B, C, D relative to the body and the relative arrangement between the electrodes, according to one embodiment. Fig. 4B shows a simplified electrical scheme showing the same relative arrangement between the electrodes shown in fig. 4A. To record the leads in the generally sagittal direction, the voltage of the lower chest electrode B relative to the center point CP can be obtained using the hand electrode C, D and the two resistors R1, R2. The two resistors R1, R2 may be equal (each about 5kΩ) or unequal (the resistor between the left hand electrode and CP is about 5kΩ and the resistor between the right hand electrode and CP is about 10kΩ). This asymmetry may reflect the left position of the heart in the torso, placing the CP point at the approximate electrical center of the heart. In this way, a substantially orthogonal three-lead configuration may be obtained.

Fig. 4C shows a spatial view of an alternative lead configuration with a center point CP, wherein the same set of chest and hand electrodes A, B, C, D are used, showing the arrangement of the electrodes relative to the body and the relative arrangement between the electrodes. Fig. 4D shows a simplified electrical scheme showing the same relative arrangement between electrodes A, B, C and D shown in fig. 4C. This alternative lead configuration using the center point CP and measuring two leads between CP and each of the chest electrodes is also substantially orthogonal, as the chest electrode A, B is used to record the leads with the reference electrode at CP obtained using the two hand electrodes C, D and the two resistors R1, R2.

Other lead configurations without center point CP and resistor may also be used, as shown in fig. 4E to record the signals of the two chest electrodes and the right hand electrode relative to the left hand electrode. Two other similar configurations are shown in fig. 4F and 4G. Such a configuration without resistors suffers less external interference (such as 50-60Hz electrical noise) but has a worse orthogonal lead direction than the previously described configuration using CP. In general, any other lead configuration using the same four described electrodes may result in non-coplanarity and as such capture diagnostic signals in all three directions, but lack high orthogonality. There are a total of 20 possible configurations without CP, including the configurations shown in fig. 4E, 4F and 4G. However, these configurations have different levels of orthogonality, depending on the use of the right hand electrode. The configuration using the right hand electrode as the common reference point in all 3 leads has the lowest orthogonality because the right hand electrode is the farthest from the heart among the four electrodes, and thus the angle between the vectors corresponding to the three leads is the smallest. The configuration using the right hand electrode in two leads (such as the configuration shown in fig. 4F) has better orthogonality, while the best orthogonality is achieved in a configuration using the right hand electrode in only one lead (such as the configurations shown in fig. 4E and 4G).

Fig. 5A, 5B and 5C show front, rear and isometric views, respectively, of an alternative embodiment of a handheld device, whereby fig. 5A shows a front view of the device in a recording position when held by a user. In an alternative embodiment, the electrode D1 for recording the ECG signal of the right arm by pressing with the right hand finger is mounted on the side 71 of the housing 31 instead of on the front surface 61 as in the above-described embodiment. Active recording electrodes A1 and B1 for recording ECG signals of the chest of a patient are mounted on the back surface 51 of the device in the same manner as in the above-described embodiments. An active recording electrode C1 for recording an ECG signal of the left hand by pressing with the left hand finger and a ground electrode G1 for pressing with the other finger of the left hand are also mounted on the front surface 61 in the same manner as above.

By having an asymmetric electrode configuration, finger swapping can be prevented so that the right hand electrode cannot be erroneously pressed by the left hand and vice versa. However, in each of the (preferred and alternative) embodiments, the upper (head facing) and lower (toe facing) portions of the device can be readily distinguished, as reversing the device would result in erroneous recordings. This may be achieved by integrating an LED diode on the front surface of the device housing on the upper or front side of the device (indicating the current recording phase).

The cardiac devices described herein (e.g., handheld, adhesive, etc.) may be implemented as stand-alone devices that include: ECG recording circuitry including amplifiers and AD converters, data storage circuitry (memory), communication circuitry operating in GSM, WWAN or similar telecommunications standards for communicating with a remote PC computer, and outputs (e.g., screen, speaker, etc.) for communicating diagnostic information to a user. In such embodiments, the apparatus may be configured to operate with a modified mobile phone that includes measurement electrodes and cardiac signal recording capabilities. Furthermore, the device may be implemented as a system attached to a mobile phone (smart phone) as a housing or an exchangeable back cover. The attached device may contain measurement electrodes and a cardiac signal recording module (including electrodes, balancing circuitry, etc.) and communicate with the mobile phone using a connector or wireless connection (such as bluetooth or ANT).

Fig. 6A, 6B and 6C show front, rear and isometric views, respectively, of another alternative embodiment of a handheld device. On the back side 52 of the device are mounted electrodes A2, B2 for contacting the chest of the patient for recording in the same way as in the preferred embodiment. On the front side 62 of the device are three electrodes: an active electrode C2, a reference electrode D2, and a ground electrode G2. All three electrodes C2, D2 and G2 have an elongated, beam-like or ribbon-like shape and are integrated on the front side 62 of the device, preferably along the two longer parallel edges of the housing 32, so as to be partly accessible from the side. In the recording position, the electrodes C2, D2, and G2 are contacted by fingers of the left hand and the right hand, respectively, in a manner equivalent to that shown for the electrodes C, D and G shown in fig. 2A. Such an electrode arrangement is suitable if the device is implemented as a modified mobile phone comprising measuring electrodes and a cardiac signal recording module, or if the device is implemented as a device attached to the mobile phone as a housing or an exchangeable back cover. In such an embodiment, the elongate electrode may be part of a frame surrounding the display of the mobile phone or tablet.

In some examples, this alternative electrode arrangement (characterized by two electrodes on one side and one electrode on the opposite side) also meets the requirement of asymmetry, avoiding the need for finger swapping.

In another alternative example, the device is a modified mobile phone having a touch screen that includes recording electrodes and a cardiac signal recording module. The three hand electrodes for pressing with the hands or fingers are realized as transparent conductive areas contained in a transparent layer covering the display of the phone, arranged in the same way as the hand electrodes in the preferred embodiment. When the cardiac signal recording application is activated, the smart phone application will mark the conductive areas on the screen with a specific color.

In another alternative embodiment, the device comprises a self-adhesive patch with chest electrodes. The self-adhesive patch is attached to the user's chest such that the same chest electrode position is achieved for the fiducial and all subsequent diagnostic recordings described above. Alternatively or additionally, an apparatus (e.g., a system) may include a patch having a docking area for connection with any device described herein that includes electrodes, which may be used to connect the device to the same location on the user's chest (or to provide a scale point reference (fiduciary reference) for the device). For example, the butt-adhesive patch may include a mating feature or region that is connected to the device to hold the chest electrode on the device in a reproducible position on the user's chest. In some variations, the docking adhesive comprises a band-aid type of material that is worn by the user over an extended period of time (e.g., hours, weeks), and may be replaced with another adhesive to maintain the same reference location.

Fig. 7 shows another embodiment of the device implemented as an extension 83 (such as a housing or interchangeable back cover) of the mobile phone in the form of a so-called flip-phone housing or wallet for the mobile phone, with chest electrodes A3 and B3 contained on the back side of the device and left and right finger electrodes C3, D3 and G3 contained in a flip-phone display cover 93 of the mobile phone housing.

Fig. 8 shows a block diagram of a method for automatically detecting AMI according to a preferred embodiment of the invention. The method for automatically detecting AMI (or ischemia) may include all or some of the steps described below. First, the device is placed in a recording position on the chest of the user.

The optimal position of the device on the chest is to center the device on the left side of the chest approximately over the center of the heart muscle. In this position, the chest electrode is approximately on the midline of the clavicle (i.e., a vertical line passing through the midpoint of the clavicle) as the V4 electrode of a conventional ECG, and the lower chest electrode is approximately at the level of the lower end of the sternum. On the front side of the device, the user presses one active electrode with the finger of the left hand and one ground electrode and one active electrode with the finger of the right hand.

The method may further comprise acquiring a first 3-lead cardiac record and communicating the signal to the processing unit. A user of the automated AMI diagnostic system may perform a recording of the 3-lead cardiac signal by holding the device against the chest for a short period of time (e.g., at least 30 seconds, at least 20 seconds, at least 10 seconds, at least 5 seconds, etc.). The record is stored in the memory of the device and then sent to the remote PC computer via the commercial communications network.

The method may further comprise storing the first record as a reference in a database of the processing unit. After performing the first transmission of his/her heart signals, the heart signal record is stored in a remote processor and the user may be registered in the diagnostic system. Prior to this first transmission, the user or his MD/nurse may enter his medical data (such as age, sex, risk factors for cardiovascular disease, etc.) and indicate whether he/she is currently suffering from chest pain or any other symptom suggesting ischemia (via a dedicated website). If the answer is negative, this first heart record is saved as a baseline record in the diagnostic system, which will serve as a reference for comparison in any additional transmissions when symptoms suggesting ischemia may occur.

The method may further comprise acquiring a 3-lead cardiac diagnostic record and communicating the signal to the processing unit. After the baseline record is accepted and stored in the database, any subsequent record is considered a diagnostic record. The user of the automated AMI diagnostic system performs a diagnostic recording of the 3-lead cardiac signal by holding the device against the chest for at least 10 seconds. The diagnostic record is stored in the memory of the device and then sent to the remote PC computer via the commercial communications network.

In general, the methods described herein may include processing, by a processing unit, signals of stored baseline records and diagnostic records. The processing may include preprocessing. For example, the apparatus/method may be configured to let Va, vb, vc be 3 specific leads recorded using the device. Before any analysis can be performed, the cardiac signal must "drop out" of interfering factors such as power line interference, baseline wander, and muscle noise. The time-averaged median heartbeat procedure is used to suppress the former two while the latter two can be removed using standard adaptive filtering techniques and cubic spline techniques, respectively.

To create a median heartbeat, the entire cardiac signal can be delineated, yielding a set of fiducial points s= { P ₁ ，P ₂ ，...，P _n }, where pi= { Q _i ，R _i ，J _i ，T _i ，T _{i, finally} The (or points equivalent to these) is the reference point for the ith beat. Based on S, the signal is then split into n individual heartbeats of the same length. Finally, the individual heartbeats are synchronized using cross-correlation (CC), and for each sample, the median of all n heartbeats is calculated. Thus, the entire cardiac signal is represented by a single, most representative, median heartbeat. The set of fiducials p= { Q, R, J, T to be associated with median heart beat _Finally Simply calculate }Is the median of the reference points of the individual heartbeats.

Techniques for obtaining representative heartbeats other than median heartbeats may also be used. The delineation of the cardiac signal yielding the fiducial point for each heartbeat may be accomplished using different techniques, such as wavelet transforms, support vector machines, etc.

The same pre-processing procedure is used for both baseline and diagnostic recordings.

If the lead recorded between the left and right hand or other lead capturing the signal in the lateral direction is reversed, the user is reminded to repeat the recording using the correct recording position.

The process may also include heartbeat alignment. For example, the apparatus or method may be configured such that B and D represent median heart beats extracted from the reference ECG and the diagnostic ECG, respectively, and PB and PD are their associated fiducial points. The goal of the heartbeat alignment is to have B and D within the same period of time so that the corresponding points are precisely synchronized. This involves finding B (called B) of such a transformation so that it is optimally synchronized with D. The transformation applied is a piecewise uniform resampling of B such that the corresponding segments in B x and D (which are defined by PB and PD, respectively) have the same number of samples. The best alignment is obtained by searching for such reference points PB that optimize the cost function or quantify the Similarity Measure (SM) of the alignment:

Then by using P _B ^* Transforming B to obtain B ^* 。

In this embodiment we use CC, which is a commonly used SM for shape-based alignment problems. However, using only CCs may result in incorrect alignment, as the shapes in B and D may be significantly different. Therefore, if the reference point P is accurately known _B We introduce a weighting function f _wi Thereby punishing with P _B Is large:

wherein i=q, R, J, T _Finally ，ΔP _Bi Is the deviation from the ith fiducial and ci is a scale factor that depends on the fiducial. That is, since the R point is the most stable reference in the ECG signal, its bias is penalized the most. On the other hand, due to J point and T _Finally The point is the least stable, thus allowing for greater deviation. Then, the overall SM is calculated as CC and a weighting function f _wi The product of the sums:

finally, B is obtained by finding the optimal value of SM given in equation (3) according to equation (1) ^* 。

The process may also include compensation for chest electrode misalignment. During normal use of the handheld device, the chest electrode may not be placed at the same location each time, thus resulting in a change in shape of the cardiac signal even without any pathology. If the lead position is assumed to be constant, the variation can be modeled as a "virtual" electrocardiographic axis deviation in the Va, vb, vc lead vector space, where the electrocardiographic axis is represented by the R vector-the cardiac vector at the time of the QRS complex (complex) having the greatest amplitude (or equivalent region of the three-lead cardiac signal described herein). However, this is an undesirable property, since the difference signal Δd will be significant even without a pathology-induced change. To overcome this problem, we transform D, producing D ^* =td such that its electrocardiographic axis is equal to B ^* Is overlapped. Using least squares and D and B ^* The Q-J segments (QRS complex) of (c) are taken as input to calculate the transform T.

In general, the processing may also include calculating a difference signal representing the change between the reference and the diagnostic 3 cardiac lead signals. By applying the difference signal DeltaD ^* The calculation is as follows:

ΔD ^* ＝D ^* -B ^* (4)

finally, this difference signal ΔD ^* Will only reflect the pathology-induced changes and it will be independent of heart axis deviations.

Since the quality of the device misalignment compensation decreases with increasing heart axis misalignment angle, if the angle change is greater than a threshold (such as 15 degrees), the user is prompted to select a position closer to the reference position.

The treatment methods and devices described herein may also include detection of changes in ischemia. In the case of ischemia, STE is the most common ECG change, typically measured at point J or up to 80 milliseconds later. In this solution, the change in ischemia is detected by comparing the test record with a reference record. In a preferred embodiment, the parameter or "marker" used for detection of ischemia is STVM (or equivalent region of cardiac signal described herein), which is the corrected difference signal ΔD at 80 milliseconds (J+80 milliseconds) after the J point ^* Vector magnitude compared to a predefined threshold (such as 0.1 mV).

In other embodiments, other points in time (such as J point, J+60 milliseconds, T _{Maximum value} Etc.) can be used as markers for ischemia. Other markers describing the shape of the ST segment (ECG signal segment between point J and point J +80 ms, or the like) may be used. Such a marker is a "coil" defined as the radius of a sphere that encloses the vector signal vector curve between the J point and the j+80 millisecond point. In addition, other composite markers may be used, such as logistic regression using a linear combination of STVM markers and coil markers.

To compensate for changes in signal shape over time, multiple fiducial recordings taken by a user over a period of time may be used to form a reference that forms a 3D contour in vector space defined by 3 particular cardiac leads (rather than a single point when a single fiducial recording is used). When such a 3D contour reference is used, the ST vector difference (STVD) will be defined as the distance from the 3D contour instead of the distance from the base ST vector. If more than one parameter is used for ischemia detection, such a reference profile will be constructed as a hypersurface in the multidimensional parameter space defined by such parameters. In this case, the hyper-distance from the reference hypersurface will be defined in the parameter space.

In users with heart conditions having intermittent signal shape changes, compensation for such changes can be done by forming two sets of fiducial recordings (at least two recordings) to define a reference, one with a normal signal and one with the condition. These two groups will form two 3D contours in vector space, forming a reference for comparison, and the ST vector difference (STVD) will be defined as the distance from the nearest point on the two 3D contours. If more than one parameter is used for ischemia detection, such a reference profile will be constructed as two hypersurfaces in the multidimensional parameter space defined by such parameters. In this case, the hyper-distance from the reference hypersurface will be defined in the parameter space.

Any of these methods and apparatus may be configured for communicating information to a device by a processing unit. The created diagnostic information may be sent from a remote processor (e.g., PC computer, server, etc.) to the device memory via a commercial communications network. The method and apparatus may also be configured for communicating diagnostic information to the patient by the device. The received diagnostic information may be presented to the user in the form of characteristic sound, speech, graphics or text.

In addition, a near conventional 12-lead ECG signal may be sent to the user's physician for evaluation. The signal may be generated by transforming the 3 specific cardiac lead signals recorded by the user into an approximate reconstruction of a conventional 12 lead. Such a reconstruction may be obtained by multiplying 3 specific cardiac leads with a 12 x 3 matrix. In one embodiment, the matrix may be calculated using conventional solutions for potential distribution on the surface of the human body (similar to those previously described for defining conventional vector electrocardiography). In another embodiment, the matrix may be obtained as a population matrix, i.e. a matrix with coefficients calculated as the mean (or median) of individual matrices obtained by simultaneously recording a population of conventional 12-lead ECG and 3 specific cardiac leads, wherein each individual matrix is obtained using the least squares method. In yet another embodiment, multiple matrices may be used in a corresponding user group defined in terms of simple parameters of body shape and structure (e.g., gender, height, weight, chest circumference, etc.) that are readily available to the user. Furthermore, matrix coefficients may be obtained as a continuous function of such body parameters.

Bonding apparatus

As described above, any of the apparatus (e.g., devices) described herein may be configured to be adhesively secured to a subject (e.g., patient), and may include two or more electrodes on the adhesive side and two or more finger electrodes (similar or identical to the handheld example) arranged as described above. These means may comprise any of the features of the described handheld device. These adhesive devices may also or alternatively be referred to as "patch" devices. Accordingly, the devices and systems described herein may include an ECG patch configured to receive and process 12-lead ECG information that may be used to detect cardiac conditions. These ECG patches may be worn for a long period of time (e.g., over 24 hours).

The ECG patches described herein address the key limitations of the prior art. As described above, for most cardiac conditions, a 12-lead ECG is diagnostically superior to a single-lead ECG. For this reason, it is the standard of care for professional medical use. Patient inconvenience associated with a 12-lead Holter (see, e.g., fig. 14) makes wearing for more than 24 hours impractical. Thus, it should be appreciated that an ECG patch for multi-week monitoring would be of great value that would combine longer-term continuous monitoring capabilities with 12-lead ECG capabilities. In addition, the patch may allow for monitoring of symptomatic episodes while the subject is wearing the patch.

As described above, in general, the methods and apparatus described herein can provide a set of substantially orthogonal electrocardiogram leads, XYZ projections of cardiac vectors, and thus allow for the synthesis (including real-time or near real-time) of 12-lead recordings as the patient experiences symptoms. The wearable patch ECG 12-lead ECG sensors described herein can have a spacing between the sensing electrodes of about 5cm and preferably 10cm or greater. To enable the ability to record the X-, Y-, and Z-projections of the cardiac vector with a patch, the patch may include an additional two finger electrodes and a resistor network within the ECG recording electronics of the patch. Any of these means may comprise a resistive network as described above.

For example, fig. 15 shows one example of an ECG patch 1500 configured for 12-lead (or 12-lead and 3-lead) detection as described herein as an adhesive chest electrode. Fig. 15 shows a bottom view of an ECG patch 1500 for 12-lead detection. A pair of chest electrodes 1507, 1509 are arranged in line, with an edge-to-edge spacing of at least 10cm. The adhesive 1501 may secure the device such that the electrodes are in electrical communication with the skin of the subject's chest. In some examples, the adhesive is a medical adhesive that can secure the device to the chest for an extended period of time (e.g., days, weeks, etc.). In some examples, the region above the electrode does not include a binder. In some examples, the area above the electrode includes an adhesive, such as a conductive hydrogel.

Fig. 16 shows a top view of the same device 1500 comprising two finger electrodes 1603, 1605. As shown, these finger electrodes are built into the top or side of the ECG patch for 12-lead detection, e.g., a non-adhesive surface. Such a configuration may ensure functionality and diagnostic performance (similar to or better than that described in, for example, the handheld device shown in fig. 13 and described in PCT/US 2020/0325556, which PCT/US2020/032556 is incorporated herein by reference). In fig. 16, the patch device further includes a body portion including one or more housings 1611, the housings 1611 may house any of the circuits discussed above (e.g., resistive networks, wireless communication circuits, etc.). The device may not include separate controls, e.g., the controls may be finger electrodes 1603, 1605, such that touching the finger electrodes may trigger recording of signals from the electrode leads, including detection of a 12-lead ECG, local (in the device) processing, storage, and/or transmission to a remote site. In some examples, the signals from the electrodes may be stored and/or transmitted for later analysis and/or review, including for later conversion to 12-lead signals. The system may also transmit the time of day. In some variations, the system may also be configured to automatically or manually detect a 1-lead ECG signal (e.g., using only two chest electrodes) or a 3-lead ECG signal. For example, the system may be configured to periodically detect electrical signals from the two (or more) chest electrodes 1507, 1509 while worn, and may store and/or transmit the sensed electrical signals and/or processed ECG signals. Alternatively or additionally, the device may include controls or inputs (e.g., from a remote device such as a smart phone or the like) for triggering measurement of single lead (or 3-lead) ECG detection. In some examples, a single lead (or 3-lead) measurement may be triggered when the user touches only one of the finger electrodes 1603, 1605. In some examples, when a user (e.g., a patient) touches multiple (e.g., two, three, or more, etc.) finger electrodes long enough, the user may trigger measurements from all leads and/or a process for obtaining a 12-lead ECG signal. During the time that the subject touches the electrodes, the system may record the signal. In some examples, the device may detect contact, for example, by a change in impedance of the electrode. Alternatively or additionally, the device may include controls (buttons, switches, etc.) that may "turn on" the device and/or move the device from standby mode to active mode. In some examples, one or both of the finger electrodes may also include a switch (e.g., a pressure-driven switch) that may turn on the device and/or move the device from a standby mode to an active mode.

In some examples, the ECG patches for 12-lead detection described herein may be referred to as "XYZ patch" devices. Typically, these devices (e.g., devices, systems, etc.) may include two finger electrodes on the top non-adhesive side of the patch, as shown in fig. 16. The finger electrodes may be adapted to contact the subject's right and left hand fingers (right hand on the right side and left hand on the left side) and may be raised slightly above the skin surface to prevent accidental contact with other parts of the body. The electrodes may be sized to fit in contact with a sufficiently large area of the finger (e.g., between 5mm-15mm in diameter), and the electrodes may be circular, square, etc.

Fig. 16 also shows a closed compartment on the upper side of the patch that also allows the left and right finger electrodes to be separated (and physically isolated). In fig. 16, a top view of the XYZ patch shows one or more housings or compartments 1611, which housings or compartments 1611 may house a power source (e.g., a battery, etc.) and/or signal acquisition and processing electronics, including a resistor network and signal storage and communication circuitry, as mentioned.

Fig. 17 shows an example of an XYZ patch worn by a patient. The orientation of the patch is shown with the right hand electrode 1603 to the right of the chest, slightly higher than the left hand electrode 1605, with the left hand electrode 1605 to the left of the chest. The measurements (which may include symptomatic events) may be detected by placing the fingers of the right and left hand on the corresponding finger electrodes. For example, in use, when a subject determines that an event may be occurring, he may place a finger on both finger electrodes. Any pair of corresponding fingers from the left and right hands (e.g., index finger, middle finger, little finger, thumb, etc.) is acceptable as long as the subject likes. In some examples, a "symptom present" button may be included on the device. Alternatively, the electrodes may be configured to detect a contact pattern from the finger, which pattern may indicate that the subject is communicating the presence of symptoms. In some examples, a patient (e.g., a subject or user) may place his/her right finger on an electrode at a higher elevation. The left finger is placed on the other finger electrode on the lower height left hand side as shown in fig. 18.

In some examples, the device may include one or more sensors to detect that the patch is properly oriented on the chest. For example, the patch may include a sensor, such as an accelerometer, for detecting the orientation of the patch on an upright (or prone in some variations) patient. Furthermore, the device may be configured to detect contact of each electrode (including the finger electrode) with the skin.

In some example operations, once skin contact is detected on both finger electrodes, the device will begin recording X, Y and Z projections of the cardiac vector and thereby be able to synthesize a 12-lead ECG signal that may correspond to a symptomatic event period. Once at least one finger is removed from the finger electrode, recording may stop and in some cases the system will continue in a single lead mode. Thus, if at least one finger is removed from the finger electrode for at least a few seconds, the recording may be stopped to avoid prematurely terminating the symptom session due to an unexpected and brief removal of the finger from the finger electrode (symptomatic session). In some examples, a 3-lead ECG measurement may be taken for a period of time when only a single finger contacts the device, and the measurement may be automatically stopped after a predetermined period of time. In some examples, after removing two fingers, additional single-lead measurements (e.g., single-lead ECG) may be made over a period of time, as this information may still be of diagnostic value.

Fig. 18 shows a symptom session record of touching the finger electrodes on the XYZ patch top surface with two fingers. Although the patch is shown in fig. 5-8 with a particular positioning and angle, it may be placed anywhere on the torso near the heart, preferably with one finger electrode at a significantly higher elevation than the other.

In order to carry the greatest diagnostic information, the XYZ leads may be as close to orthogonal as possible (e.g., three vector axes, each at a 90 degree angle therebetween). Contrary to the orthogonality is the case of three co-planar vectors, i.e. three vectors in the same plane, in which case the diagnostic information corresponding to the axis perpendicular to this plane is completely lost.

The above-described four recording electrode configuration with two chest electrodes and two finger electrodes satisfies the requirement of high orthogonality. As mentioned above, a simple way to meet this requirement is to record signals in three main body directions: transverse (left arm-right arm), sagittal (posterior-anterior), and caudal (cephalad-toe). For example, the signal in the transverse direction is obtained by measuring the lead between the left and right hand, and the signal in the caudal direction is obtained by measuring the lead between the two chest electrodes, provided that the vertical distance between the chest electrodes is at least 5cm (and preferably greater than about 10 cm) so as to be greater than the approximate diameter of the heart muscle. In an ideal case, the sagittal signal would be measured between the back and chest of the patient, which is not possible with the limitation of using only finger and chest electrodes. To overcome this, a simple resistor network is used to make a reference point near the electrical center of the heart, as described below. See also US10,117,592B2, which is incorporated by reference in its entirety.

The above description may explain why for maximum orthogonality of the recorded signals, the preferred attachment position of the patches is that the electrodes are substantially directly above each other (vertical position of the patches). As mentioned, this can be ensured by using an accelerometer built in. Such a position of the patch on the torso of a patient is shown in fig. 19. Although the compactness of the XYZ patch requires the finger electrodes to be placed on the top or side surfaces of the patch, in some examples the finger electrodes may be designed as part of a separate pair of electrodes attached to the chest and patch. Alternatively, as will be described below in fig. 21A-21C, additional adhesive electrodes may be placed on the limb (as limb electrodes, e.g., on or near the shoulders) and may be used without the need for finger electrodes.

Any method of attaching the finger electrodes to the patch may be used as long as two fingers are used in addition to the two chest patch electrodes. The XYZ patches described herein can enable real-time or near real-time analysis of symptomatic events. Unlike prior art devices, in which the entire set of multi-week records is sent for analysis after the device is removed from the patient's chest, the apparatus described herein may operate in more real-time. These devices may allow for minimal analysis time and possible diagnosis and intervention when reviewing potential symptomatic events. In some examples, the descriptions and corresponding ECG waveforms may be wirelessly transmitted in real-time or near real-time for specialized medical assessment. As used herein, real-time may include near real-time (e.g., within a few minutes).

Fig. 20A schematically shows a schematic diagram of the system, which is shown as a system flow diagram of an example of an XYZ patch. In fig. 20A, ECG signal sampling 2001, processing 2003, buffering 2005 and/or compression 2007 may be accomplished in any standard manner based on signals detected by various electrode pairs (chest/chest, chest/left finger, chest/right finger, center point/left finger, center point/right finger, etc.). For example, the sample signal may be stored and/or processed on an on-board circuit (e.g., memory). In some examples, a sample may be classified as part of a symptom onset or part of a conventional asymptomatic single lead ECG recording segment (section) before it is written into an on-board flash memory. Whether the sample is part of a symptom onset can be determined based on whether the patient presses a "symptom present" dedicated button or simply by detecting skin contact on both finger electrodes (as shown in fig. 18). In the latter case, when symptoms are present, the patient may be instructed (e.g., by a signal, such as a tone or other sound, one or more LEDs, etc.) to touch the finger electrode and hold the finger on the finger electrode. When the patient's finger touches the finger electrode, the system can record 3 channels: an X component, a Y component, and a Z component of the cardiac vector. Alternatively or additionally, in some examples, the device may detect a dangerous cardiac rhythm while periodically or continuously monitoring the patient (e.g., using only two or more chest electrodes, such as a 1-lead electrode). If a dangerous or irregular cardiac signal (e.g., irregular rhythm, AMI, tachycardia, etc.) is detected, the device may alert the user (via tone, text/SMS, vibration, etc.) to place their finger on the electrode (indicating "symptom present" 2011), as described in more detail below. Thus, in general, any of these devices and methods may include ongoing, periodic, or continuous monitoring by the system.

In some examples, the digital samples may be written to an on-board flash memory. Once the flash memory is removed from the patch, it may be physically or electronically shared with a facility capable of analyzing all records. Of particular interest are signal segments of the signal that may be associated with symptomatic attacks. These episodes may characterize the XYZ signal and be converted from the XYZ signal to a 12-lead ECG signal, which is then analyzed.

All or some of the ECG signal samples may be streamed in real-time to a communication device, such as a smart phone, which in turn communicates with a server, or by means of a built-in communication module that communicates directly with a cloud-based server. The system is capable of transmitting all of the recorded signals in real time. As highlighted above, of particular interest are symptomatic episodes recorded with patches.

For example, returning to fig. 20A, the methods described herein may detect the presence of a finger on the electrode 2011, as discussed above 2011, and may indicate (e.g., may mark 2015) that a signal is being recorded and marked as potentially including a heart difficulty (cardiac difficulty) episode or not including a heart difficulty episode 2013. As mentioned, the signal may be annotated (e.g., with date, time, skin impedance data, etc.) and stored in a device memory storage (device memory storage) (such as flash memory 2017) and/or processed 2019 as discussed above.

In some examples, to save power and/or time, the system may store all samples associated with a symptom onset in a dedicated memory sector or be able to fetch samples from memory based on a unique signature of a particular symptom onset. These samples may be buffered 2021 and/or transmitted 2023 in real time via on-board (to-chip) communications hardware and software. For example, a bluetooth connection from the patch to the patient's smart phone may be used for symptom session signaling, and an internet connection of the phone may be used for transmission onto the cloud. The initial automated diagnostic signal analysis may be performed in the cloud and transmitted from the cloud to an analysis facility for timely analysis by a professional medical professional.

Rather than downloading all signal samples and then sending them for analysis after a delay (e.g., two weeks or more), the methods and apparatus (e.g., systems) described herein can sample ECG (and in some examples perform analysis) and transmit the samples (and/or analysis) in real-time for review by a physician. This real-time symptom onset analysis is an improvement over current practice.

For each symptom session, the patient may be required to report the associated symptom. This may be accomplished by voice recording and/or forms with standard questions, or even by free-form written reports of the patient on their smartphone.

Fig. 20A also depicts a real-time analysis of symptom onset. By setting the symptom flag (e.g., to 1), the XYZ signal 2025 recorded in the symptom session can be marked as symptomatic. In a next step, they may be sent to the cloud where they are converted into the derived 12-lead ECG 2027. Typically, an automated diagnostic analysis 2029 performed in the cloud follows. Alternatively or additionally, both the derivation of the 12 leads and the diagnostic analysis may be performed by software resident on the patient's smartphone. One component of the signal analysis may be the review of the recorded ECG signal by a trained medical professional after the computerized analysis is completed.

Fig. 20B illustrates another example of a method of operating a device as described herein, and in particular, a method of operating an adhesive attachment device comprising one or more arm electrodes, as described in fig. 21A-21C, described in more detail below. In these examples, the device may not require finger contact to derive the 12-lead ECG signal.

For example, in fig. 20B, the device may be configured to periodically or continuously monitor electrical signals from two or more chest electrodes and one or more arm electrodes on an adhesive patch (such as the adhesive patch shown in fig. 12A-12C). In one variation, the system may monitor for activation of a user-activated "symptom present" button and may then detect an ECG signal, which may be configured as a 12-lead ECG signal. In fig. 20B, as described for fig. 20A, ECG signal sampling 2051, processing 2053, buffering 2055, and/or compression 2057 may be performed in any standard manner based on signals detected by various electrode pairs (chest/chest, chest/left arm, chest/right arm, center point/left arm, center point/right arm, etc.). For example, the sample signal may be stored and/or processed on an on-board circuit (e.g., memory). In some examples, the sample may be classified as part of a symptom onset or part of a conventional asymptomatic single lead ECG recording segment before it is written to the on-board flash memory. Whether the sample is part of a symptom onset may be determined based on whether the patient presses a "symptom present" dedicated button.

When the patient/user experiences symptoms of a cardiac event, she or he may activate the detect symptoms control ("detect symptoms button") 2061. As mentioned, the apparatus may monitor the patient wearing the device continuously or periodically (e.g., every few seconds, every 10 seconds, every 15 seconds, every 30 seconds, every minute, every 2 minutes, every 5 minutes, every 7 minutes, every 8 minutes, every 9 minutes, every 10 minutes, every 15 minutes, every 30 minutes, etc.), and may detect irregular cardiac signals (e.g., AMI, tachycardia, etc.). In some cases, if the device automatically detects an irregular cardiac signal when symptoms are present, the patient may be instructed to touch a symptom presence indicator (button, control, dial, etc.). Alternatively, when using a patch with a front finger electrode, detection of an irregular heart signal may prompt the patient to touch the finger electrode with their finger (as shown in fig. 18). Alternatively or additionally, in some examples, the device may detect a dangerous cardiac rhythm while periodically or continuously monitoring the patient. If a dangerous rhythm (e.g., irregular rhythm, AMI, tachycardia, etc.) is detected, the device may flag the particular detected signal as potentially indicative of a symptom (e.g., by triggering symptom flag 2065) and/or alert the caregiver and/or user (via tone, text/SMS, vibration, etc.). In particular, a patch such as that shown in fig. 21C may be used to continuously monitor heart activity of a patient in order to detect AMI. The orthogonal guide system described above can be readily acquired by the patch of fig. 21C on a periodic or continuous basis. Algorithms described herein may then be employed to detect the occurrence of an AMI event and trigger an appropriate alarm. Thus, in general, any of these devices and methods may include ongoing, periodic, or continuous monitoring by the system.

If the system does not detect an irregular heart signal and/or the user does not activate the symptom presence button, the device may set the symptom flag to null 2063 and may in some cases acquire the reference signal 2068. The system may use the fiducial in a patient-specific manner to improve detection of irregular cardiac signals and/or 12-lead ECG. The reference signal may be determined at a certain frequency (e.g., every minute, every few minutes, every 2 minutes, every 5 minutes, every 10 minutes, every 15 minutes, every 20 minutes, every 30 minutes, every 45 minutes, every hour, every 2 hours, every 4 hours, every 8 hours, every 12 hours, every day, every 2 days, every 5 days, every 7 days, etc.).

As mentioned, the digital samples may be written into an on-board flash memory 2067 and/or transmitted 2073 (e.g., after signal processing such as buffering 2071, etc.). Once the flash memory is removed from the patch, it may be physically or electronically shared with a facility capable of analyzing all records. Of particular interest are signal segments of the signal that may be associated with symptomatic attacks. These signals can be used to generate a 12-lead ECG signal 2075 from a subset of the recorded leads. Signal analysis may be used to interpret the 12-lead ECG signal 2077, including detection of heart attacks. These episodes may characterize the XYZ signal and be converted from the XYZ signal to a 12-lead ECG signal, which is then analyzed.

All or some of the ECG signal samples may be streamed 2073 in real-time or near real-time (or after storage) to a communication device, such as a smart phone, which in turn communicates with a server, or in real-time or near real-time by means of a built-in communication module that communicates directly with a cloud-based server. The system is capable of transmitting all of the recorded signals in real time. As highlighted above, of particular interest are symptomatic episodes recorded with patches.

For example, in fig. 20B, the methods described herein may detect and record signals, and one or more signals may be marked as potentially including a heart attack 2063 (or may be marked as not indicating heart difficulty). As mentioned, the signals may be annotated (e.g., with date, time, skin impedance data, etc.) for transmission and/or stored in a device memory storage (such as flash memory 2067) and/or processed 2069 as discussed above.

In some examples, to save power and/or time, the system may store all samples associated with a symptom onset in a dedicated memory sector or be able to fetch samples from memory based on a unique signature of a particular symptom onset. These samples may be buffered 2061 and/or transmitted 2063 in real-time via on-board (to-chip) communication hardware and software. For example, a bluetooth connection from the patch to the patient's smart phone may be used for symptom session signaling, and an internet connection of the phone may be used for transmission onto the cloud. The initial automated diagnostic signal analysis may be performed in the cloud and transmitted from the cloud to an analysis facility for timely analysis by a professional medical professional.

Once the patch has been worn by the patient, the entire contents of the multi-day recording can be analyzed in a number of different ways. While real-time transmission and analysis of signals associated with symptomatic attacks is highly desirable, this is not mandatory and may be deferred until such time as the patch is removed from the patient's body.

As mentioned, the patch devices described herein may be fabricated using a simple resistive network to create a Center Point (CP) near the electrical center of the heart. To record the leads in the general sagittal direction, we recorded the voltage of the lower chest electrode relative to the Center Point (CP) obtained using two hand electrodes and two resistors. The two resistors may be equal (each about 5 kiloohms (kΩ)) or unequal (the first resistor between the left hand electrode and CP is about 5 kiloohms (kΩ), and the second resistor between the right hand electrode and CP is about 10 kiloohms (kΩ)). This asymmetry reflects the left position of the heart in the torso, moving the CP to approximately the electrical center of the heart. In this way we obtain a substantially orthogonal three-lead system. Other lead configurations with or without CP may also be used.

The XYZ patch may comprise: a heart signal recording circuit including an amplifier and an AD converter for amplifying a signal detected by the electrodes; a data storage circuit (e.g., a memory) for storing the recording signal; communication circuitry operating on a GSM, WWAN, or similar telecommunications standard for communicating with a remote processor (e.g., PC computer, tablet, smart phone, etc.); and circuitry (e.g., screen, speaker, etc.) for communicating diagnostic information to a user in the form of visual and/or audio output.

A handheld device with a special electrode configuration is able to record three orthogonal cardiac lead signals in an orientation-specific manner and transmit these signals to a processor (e.g., a PC or other computing device). The remote processor may be configured to diagnose/detect the AMI and transmit diagnostic information back to the handheld device.

The remote processor may be equipped with diagnostic software for processing the received cardiac signals, generating diagnostic information, and for transmitting the information back to the handheld device for communicating the diagnostic information to the patient. The device may perform automatic detection of heart conditions on the basis of a 3-lead system and may not require interpretation of the processed diagnostic information by an expert.

The signal processing and diagnostic software may also run on a processor (e.g., a microprocessor) integrated in the housing of the handheld device for processing the recorded cardiac signals and generating diagnostic information. When the diagnostic process is performed by the remote processor, a backup version of the software running on the microprocessor may be integrated in the handheld device and used when the user is in an area that is not covered by the wireless network.

The device may communicate with a remote processor via an integrated communication circuit. The remote processor may communicate with the handheld device via the integrated communication module. The created diagnostic information may be transferred from a remote processor (e.g., PC computer, server, etc.) to the device memory via a commercial communications network. The handheld device may communicate the diagnostic information to the patient in the form of graphical information via a characteristic sound, a voice message via an acoustic sensor that produces the characteristic sound, or via a display integrated in the device.

In general, the analysis may include analysis of a benchmark. The reference ECG (e.g., reference heart vector) may be acquired when the patient first orders and/or purchases the device. The reference signal may be checked by the system. For example, the reference signal may be checked to confirm that it is within some predefined "normal" parameter range. For example, the reference signal of the present patent may be determined by differential vector analysis of a reference cardiac vector determined from three orthogonal leads of the signal collection device. Multiple reference measurements may be made and averaged, or the best one may be selected. In the event that the baseline does not fall within the expected parameters, for example, the patient may be rejected as a poor candidate because the patient has an irregular cardiac vector for some reason, including concurrent, undetected cardiac events. The system may periodically prompt the user to provide an updated reference signal.

In some variations, the application software may provide a Quality Control (QC) to check the signals (e.g., QC agents, software agents, etc.), which may indicate whether the reference cardiac vector is adequate; this may be done in real time and may include a signal quality check, which may be done at one or both of the signal collection device and the mobile communication device (e.g., smart phone), and/or may be done at a remote server. The QC proxy may look for clarity of the signal and/or may also confirm that the patient is not suffering from a heart attack. This may be part of a final level quality check.

The application software/firmware may also collect risk factors from the patient. This may advantageously be done at the time of subscription. The patient may be prompted for a series of questions and/or access to electronic medical records may be provided to indicate risk factors associated with heart disease (e.g., heart attack, etc.). The information may include patient-specific information (age, gender, weight, height, race, cholesterol level, blood pressure, etc.). Queries may be ordered and weighted. Minimal input of risk factor information (e.g., age only, age and gender only, etc.) may be allowed; if a minimum is not entered, the patient may not be allowed to order.

As mentioned, the application may prompt the patient to update the benchmark periodically (e.g., weekly, twice a month (bimonthly), monthly, etc.) by sending a message (SMS/text message) in the associated application software (app) or without the app (from a remote server).

In some variations, the physician may be reported, then the physician may interpret the results, including risk factors and symptoms, manually or semi-manually, and the physician may contact the patient directly, including through the app.

For example, a mobile three-lead cardiac monitoring device having a first compact and undeployed (undeployed) configuration and a second deployed (deployed) configuration as described herein may be configured to be operated by a patient when a cardiac symptom occurs. The apparatus may include a storage device (e.g., memory) for storing data regarding cardiac risk factors of the patient and other data, a cardiac signal recording component (e.g., electrodes, circuitry, controller) for recording cardiac signals of the patient; the recording components may be similar to those disclosed in WO2016/164888A1 to Bojovic et al, mentioned above. By equipping the device with a graphical user interface (e.g., a touch screen or screen and keyboard, etc.), patient-related data (risk factors and current symptoms) can be entered and diagnostic messages can be communicated to the patient. Diagnostic information may also or alternatively be communicated to the patient by a characteristic sound or voice message via a speaker. The communication may occur via a wired or wireless connection with a separate user-operated device, such as a smart phone or tablet computer, etc.

As mentioned, in some examples, a four recording electrode configuration (e.g., with two chest electrodes and two finger electrodes) may satisfy the condition of high orthogonality, for example, by recording signals in three main body directions: transverse (left arm-right arm), sagittal (posterior-anterior), and caudal (cephalad-toe). For example, a signal in the lateral direction may be obtained by measuring a lead between the left hand and the right hand. The signal in the caudal direction can be obtained by measuring the lead between two chest electrodes, with the proviso that the distance between the chest electrodes in the caudal direction is at least 5cm, preferably more than about 10cm, so as to be larger than the approximate diameter of the heart muscle. Ideally, the sagittal signal would be measured between the patient's back and chest, using a simple resistive network to make a Center Point (CP) near the electrical center of the heart. To record the leads in the general sagittal direction, we recorded the voltage of the lower chest electrode relative to the Center Point (CP) obtained using two hand electrodes and two resistors. The two resistors may be equal (each about 5 kiloohms) or unequal (the first resistor between the left hand electrode and CP is about 5 kiloohms and the second resistor between the right hand electrode and CP is about 10 kiloohms). This asymmetry reflects the left position of the heart in the torso, moving the CP to approximately the electrical center of the heart. In this way we obtain a substantially orthogonal three-lead system.

Other similar lead configurations with the same CP may be selected using the same set of two chest electrodes and two hand electrodes. Such a lead configuration may be substantially orthogonal, for example, when two chest electrodes are used to record the leads using a reference pole at CP. Another possible way of defining CP is to use three electrodes (two hand electrodes and one chest electrode) and 3 resistors connected in a Y (star) configuration.

Other lead configurations without CP may also be used, as may configurations that record signals of two chest electrodes and a right hand electrode relative to a left hand electrode. This configuration without resistors or CP has a higher immunity to electrical noise, e.g., 50-60Hz, but has a worse orthogonal lead direction than the described configuration using CP. In general, any other lead configuration using the same four described electrodes (20 configurations without CP in total) results in non-coplanar leads, and as such diagnostic signals are captured in all three directions, but may lack a high degree of orthogonality. However, these configurations may have different levels of orthogonality depending on the use of the right hand electrode. The configuration using the right hand electrode as a common reference point among all 3 leads may have the lowest orthogonality because the right hand electrode is the farthest from the heart among the four electrodes, and thus the angle between vectors corresponding to the three leads is the smallest. However, this configuration with minimal orthogonality is optimal for a 12-lead ECG reconstruction based on a 3-lead signal due to its small non-dipole content. However, signals obtained using this configuration may be used with or without 12-lead reconstruction.

For example, the devices described herein may be used for remote diagnosis of cardiac conditions such as Acute Myocardial Infarction (AMI), atrial fibrillation (AFib), and the like. In particular, described herein are handheld devices having a particular electrode configuration that is capable of recording three orthogonal cardiac lead signals in an orientation-specific manner and transmitting those signals to a processor (e.g., a PC or other computing device). The processor may be configured to diagnose/detect AMI and send diagnostic information back to the handheld device. The handheld device may communicate diagnostic information to the patient via a unique sound, voice message, or via a graphical display. The processor may be configured via hardware, software, firmware, etc., and may process the received signals to generate a difference signal and extract information reliably related to the detection of AMI (and additional information of clinical relevance). Thus, these devices and methods can perform automatic detection of heart symptoms on a 3-lead system basis without the need for a 12L ECG reconstruction, reducing or eliminating the need for medical personnel to interpret ECG, unlike prior art systems which typically rely on medical personnel to make such decisions. The automated diagnostic methods described herein, in combination with the improved handheld cardiac device, address many of the needs and problems that exist in other systems.

The patch devices described herein may be positioned on the chest with the center of the device on the left side of the chest, generally above the center of the heart muscle. In this position, the chest electrode is approximately on the midline of the clavicle (i.e., a vertical line passing through the midpoint of the clavicle) as the V4 electrode of a conventional ECG, and the lower chest electrode is approximately at the level of the lower end of the sternum. The signal in the lateral direction can be obtained by measuring the lead between the left hand and the right hand. The signal in the caudal direction can be obtained by measuring the lead between two chest electrodes, with the proviso that the distance between the chest electrodes in the caudal direction is at least 5cm, preferably more than about 10cm, so as to be larger than the approximate diameter of the heart muscle.

As already described above, the example in fig. 3A shows a simple electrical scheme for obtaining the center point CP by connecting the electrodes of both hands via a simple resistive network with two resistors. Alternatively, the operational amplifier scheme in fig. 3B may be used. The same configurations shown and described above in fig. 3, 4A-4G may be used with any of the bonding devices described herein. For example, to record a lead in the generally sagittal direction, the voltage of the lower chest electrode B relative to the center point CP may be obtained using the hand electrode C, D and the two resistors R1, R2. The two resistors R1, R2 may be equal (each about 5kΩ) or unequal (the resistor between the left hand electrode and CP is about 5kΩ and the resistor between the right hand electrode and CP is about 10kΩ). This asymmetry may reflect the left hand position of the heart in the torso, placing the CP point at the approximate electrical center of the heart. In this way, a substantially orthogonal three-lead configuration may be obtained.

Example

Fig. 21A illustrates another example of a patch (e.g., adhesive) device for long-term monitoring and detection of a 12-lead equivalent ECG. In fig. 21, instead of coupling all of the finger electrodes to the same housing, the patient (or caregiver or medical professional) may individually attach a housing 2105 having at least two skin contact ("chest") electrodes to a separate patch 2107 that includes a second finger electrode and/or arm electrode 2125, the housing 2105 may be coupled by leads 2108 that connect the chest electrodes 2117, 2119 (and one or more finger electrodes 2121). In some examples, a separate patch may be adhesively secured to the shoulder or arm (e.g., left shoulder/arm) and used in place of the derived arm leads. The second finger electrode 2123 in this example may be omitted or may be used as a reference.

Fig. 21B shows another example 2105' of a patch device having a central (cardiac) patch region, the patch device being electrically coupled to a pair of separate finger or arm patches 2107', 2107 "via a pair of tethers 2108, 2108 '. In this example, each arm patch may be attached to a shoulder or arm of a subject for measuring leads from each arm, rather than deriving leads from finger electrodes. Optional finger electrodes 2123', 2123 "may also be included. In fig. 21A-21B, the thickness of the patch is not shown to scale, but is shown schematically exaggerated. The patch may be made of a flexible and relatively thin material.

In some variations, it may be beneficial to include a single sheet that adheres to the skin, rather than two or more separate adhesive patches. For example, fig. 21C shows an example of a patch device that may include extensions (arms, wings, etc.) for adhesively securing arm electrodes to right (e.g., shoulders) and left (e.g., shoulders) arm regions. In fig. 21C, the bottom of the device is shown, showing electrodes, including chest electrodes 2117", 2119", left arm electrode 2123' "and right arm electrode 2123" ". The housing portion 2135 of the device may be offset relative to the two arm electrodes (e.g., so as to be positioned over the heart area of the chest when worn). In some examples, the device may also include one or more controls, such as buttons, which may be on the non-adhesive side (not shown), which may allow the device to be triggered to record or associate records as events. The examples shown in fig. 21A-21C may allow for continuous or periodic 12-lead ECG detection without requiring the user to touch the finger electrodes. Thus, a baseline 12 lead ECG measurement may be obtained and used to normalize or adjust the measurement to improve accuracy. The device shown in fig. 21C may be provided in various predetermined sizes (e.g., small, medium, large) and/or may be adjustable.

The example shown in fig. 21C is a continuous patch, with arm extensions 2130, 2132 extending from a central chest area applied as described above. As mentioned, in some examples, the left arm extension 2130 may be shorter or longer than the right arm extension 2132, or they may be the same size. For example, in some cases, the left arm extension (which would be worn on the left side of the patient's chest) is shorter so that the chest electrode can be located more closely above the heart. The chest arm extension may be between 2 inches and 12 inches long, for example; the total length (from the left arm electrode to the right arm electrode) may be between 6 inches and 16 inches (e.g., between 8 inches and 16 inches, between 6 inches and 15 inches, between 7 inches and 14 inches, etc.).

As described above, an adhesive patch apparatus such as that shown in fig. 21C may operate as described above in fig. 20B.

Clinical studies were conducted to evaluate the diagnostic accuracy of the above-described method for detecting myocardial ischemia caused by coronary balloon dilation during a PCI (percutaneous coronary intervention) procedure. A device similar to that shown in fig. 2C is used.

In this example, the data is acquired continuously. Continuous data from a standard 12-lead ECG and three additional specific leads were obtained from each patient during the entire balloon occlusion period and during the short periods before and after. If the patient is stable, the target duration of balloon occlusion is at least 90 seconds. In each patient, a baseline record was taken before the PCI procedure was started, and a pre-dilation was performed during the procedure (before the first balloon insertion). At each lesion/intervention site, an expansion record was taken just prior to balloon deflation. The data set analyzed contained 66 patient ECG recordings and 120 balloon occlusions (up to three dilated arteries per patient).

The data were analyzed by the method described above (using an example with a linear combination of STVM and "coil" markers) and the results were compared with the interpretation of the same data set by three experienced cardiologists (one interventional cardiologist, two cardiac electrophysiologists) regardless of any clinical data. All dilation recordings were assumed to be ischemic positive and all pre-dilation recordings were assumed to be ischemic negative. The study dataset was divided into two sets of approximately the same size, a study set and a test set (using a random number generator). The markers for ischemia detection are selected and the marker threshold is tuned to the learning set before the algorithm is applied to the test set.

Table 1 below shows the results of the present study comparing the automatically scored readings to the readings of the human (e.g., cardiologist) score, and to the success rate of a trained human expert (average of human readers), using the automated method described herein, showing a higher success rate.

	Sensitivity [%]	Specificity [%]	Accuracy [%]
				Automatic method	89.06	91.18	89.80
Human readers	76.11	64.14	71.86
				Difference value	12.95	27.04	17.93

Table 1: sensitivity, specificity and accuracy of the automated method compared to human expert readings.

The results presented in table 1 show the superiority of using the availability of reference baseline cardiac recordings to distinguish between old and new ST deviations.

Another clinical study was conducted to evaluate the diagnostic accuracy of an algorithm based on 3 orthogonal cardiac leads in detecting atrial fibrillation. The dataset included 453 recordings from 25 patients (227 recordings with sinus rhythm and 226 recordings with atrial fibrillation) after pulmonary vein separation (Pulmonary Vein Isolation). The "coil" tag was applied to the P-wave and combined with the usual RR-spacer tag. Table 2 below shows the results of this study.

	Sensitivity [%]	Specificity [%]	Accuracy [%]
				Automatic method	99.12	92.04	95.58

Table 2: performance of automated methods in detecting atrial fibrillation

Any of the methods described herein (including user interfaces) may be implemented as software, hardware, or firmware, and may be described as a non-transitory computer-readable storage medium storing a set of instructions capable of being executed by a processor (e.g., a computer, a tablet, a smartphone, etc.), which when executed by the processor, cause the processor to perform any of the steps, including, but not limited to: display, communicate with the user, analyze, modify parameters (including timing, frequency, intensity, etc.), determine, alert, or the like.

When a feature or element is referred to herein as being "on" another feature or element, it can be directly on the other feature or element or intervening features and/or elements may also be present. In contrast, when a feature or element is referred to as being "directly on" another feature or element, there are no intervening features or elements present. It will also be understood that when a feature or element is referred to as being "connected," "attached," or "coupled" to another feature or element, it can be directly connected, attached, or coupled to the other feature or element, or intervening features or elements may be present. In contrast, when a feature or element is referred to as being "directly connected," "directly attached," or "directly coupled" to another feature or element, there are no intervening features or elements present. Although described or illustrated with respect to one embodiment, the features and elements so described or illustrated may be applied to other embodiments. Those skilled in the art will also recognize that a reference to a structure or feature that is disposed "adjacent" another feature may have portions that overlap or underlie the adjacent feature.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. For example, as used herein, the singular forms "a," "an," and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and/or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and/or groups thereof. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items, and may be abbreviated as "/".

Spatially relative terms, such as "under", "below", "lower", "above", "upper" and the like, may be used herein to describe easily the relationship of one element or feature to another element(s) or feature(s) as illustrated in the figures. It will be understood that spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures. For example, if the device in the figures is turned over, elements described as "below" or "beneath" other elements or features would then be oriented "above" the other elements or features. Thus, the exemplary term "below" may encompass both an orientation of above and below. The device may be otherwise oriented (rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly. Similarly, the terms "upwardly ()", "downwardly (vertical)", "vertical", "horizontal" and the like are used herein for purposes of explanation only, unless otherwise specifically indicated.

Although the terms "first" and "second" may be used herein to describe various features/elements (including steps), these features/elements should not be limited by these terms unless otherwise indicated by the context. These terms may be used to distinguish one feature/element from another feature/element. Thus, a first feature/element discussed below could be termed a second feature/element, and, similarly, a second feature/element discussed below could be termed a first feature/element, without departing from the teachings of the present invention.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to mean that the various components may be used in both methods and articles of manufacture (e.g., compositions of matter and devices including apparatus and methods). For example, the term "comprising" will be understood to imply the inclusion of any stated element or step but not the exclusion of any other element or step.

In general, any apparatus and method described herein should be understood to be inclusive, but that all or a subset of the elements and/or steps may, alternatively, be referred to as "consisting of, or alternatively, consisting essentially of, the various elements, steps, sub-elements, or sub-steps.

As used herein in the specification and claims, including in the examples, and unless otherwise expressly specified, all numbers may be considered as if prefaced by the word "about" or "about," even if the term does not expressly appear. The phrase "about" or "approximately" may be used when describing an amplitude and/or position to indicate that the value and/or position described is within a reasonably expected range of values and/or positions. For example, a numerical value may have a value of +/-0.1% as stated value (or range of values), +/-1% as stated value (or range of values), +/-2% as stated value (or range of values), +/-5% as stated value (or range of values), +/-10% as stated value (or range of values), etc. Any numerical value set forth herein should also be understood to include about or approximately that value unless the context indicates otherwise. For example, if the value "10" is disclosed, then "about 10" is also disclosed. Any numerical range recited herein is intended to include all sub-ranges subsumed therein. It is also understood that when a value is disclosed, "less than or equal to" the value, "greater than or equal to" the value, and possible ranges between the values are also disclosed, as would be well understood by one of ordinary skill in the art. For example, if the value "X" is disclosed, then "less than or equal to X" and "greater than or equal to X" (e.g., where X is a numerical value) are also disclosed. It should also be understood that throughout this application, data is provided in a variety of different formats, and that the data represents ranges for endpoints and starting points, and for any combination of the data points. For example, if a particular data point "10" and a particular data point "15" are disclosed, it is to be understood that greater than, greater than or equal to, less than or equal to, and equal to 10 and 15, and 10 to 15 are disclosed. It should also be understood that each unit between two particular units is also disclosed. For example, if 10 and 15 are disclosed, 11, 12, 13 and 14 are also disclosed.

While various illustrative embodiments have been described above, any of several modifications may be made to the various embodiments without departing from the scope of the application as described in the claims. For example, in alternative embodiments, the order in which the various described method steps are performed may generally be changed, and in other alternative embodiments, one or more method steps may be skipped altogether. Optional features of the various device and system embodiments may be included in some embodiments and not in others. Accordingly, the foregoing description is provided primarily for illustrative purposes and should not be construed to limit the scope of the application as set forth in the claims.

The examples and descriptions included herein illustrate, by way of illustration and not limitation, specific embodiments in which the subject matter may be practiced. As noted, other embodiments may be utilized and derived therefrom, such that structural and logical substitutions and changes may be made without departing from the scope of this disclosure. Such embodiments of the inventive subject matter may be referred to herein, individually or collectively, by the term "application" merely for convenience and without intending to voluntarily limit the scope of this application to any single application or inventive concept if more than one is in fact disclosed. Thus, although specific embodiments have been illustrated and described herein, any arrangement calculated to achieve the same purpose may be substituted for the specific embodiments shown. This disclosure is intended to cover any and all adaptations or variations of various embodiments. Combinations of the above embodiments, and other embodiments not specifically described herein, will be apparent to those of skill in the art upon reviewing the above description.

Claims

1. A method, the method comprising:

adhering a patch to a chest of a patient such that a first electrode and a second electrode integrated on a back side of the patch measure bioelectrical signals from the chest of the patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart;

shortly after adhering the patch to the chest of the patient, obtaining a reference Electrocardiogram (ECG) when the patient contacts a third electrode on the patch with a finger of a first hand and a fourth electrode on the patch with a finger of a second hand, wherein the reference ECG comprises three orthogonal or quasi-orthogonal leads generated from the first electrode, the second electrode, the third electrode, and the fourth electrode; and

when the patient indicates no symptoms on the patch, then on a subsequent day or more, the reference ECG is updated when the patient contacts the third electrode on the patch with the finger of the first hand and the fourth electrode on the patch with the finger of the second hand, wherein the reference ECG recording includes three orthogonal or quasi-orthogonal leads generated from the first electrode, the second electrode, the third electrode, and the fourth electrode.

2. The method of claim 1, further comprising storing the reference ECG.

3. The method of claim 1, further comprising recording a symptomatic ECG when the patient indicates the presence of symptoms on the patch, wherein symptomatic ECG recordings include three orthogonal or quasi-orthogonal leads generated from the first electrode, the second electrode, the third electrode, and the fourth electrode.

4. The method of claim 3, further comprising automatically detecting irregular cardiac signals from the symptomatic ECG using the reference ECG recording.

5. The method of claim 3, further comprising displaying the symptomatic ECG superimposed with the reference ECG.

6. A method according to claim 3, wherein the patient indicates the presence of symptoms on the patch by activating a button on the patch.

7. The method of claim 1, wherein the patient indicates the absence of symptoms on the patch by activating a button on the patch.

8. The method of claim 1, wherein the patient indicates the absence of symptoms on the patch by not activating a button on the patch indicating the presence of symptoms.

9. The method of claim 1, wherein acquiring the reference ECG includes processing bioelectrical signals from the first electrode, the second electrode, the third electrode, and the fourth electrode using a processing network to form the three orthogonal leads, the processing network forming a center point of transfer between the third electrode and the fourth electrode in a sagittal plane passing through the patient's chest while the patch remains adhesively secured to the patient's chest, wherein three orthogonal cardiac leads are formed by the electrodes and the center point.

10. The method of claim 1, wherein updating the reference ECG includes detecting finger contact on both the third electrode and the fourth electrode using a detection circuit.

11. The method of claim 1, further comprising converting the three orthogonal or quasi-orthogonal leads to a 12-lead ECG signal.

12. A method, the method comprising:

Shortly after adhering the patch to the chest of the patient, obtaining a reference Electrocardiogram (ECG) when the patient contacts a third electrode on the patch with a finger of a first hand and a fourth electrode on the patch with a finger of a second hand, wherein the reference ECG comprises three orthogonal or quasi-orthogonal leads generated from the first electrode, the second electrode, the third electrode, and the fourth electrode;

storing the reference ECG;

updating the reference ECG when the patient indicates no symptoms on the patch, then on a subsequent day or more, when the patient contacts the third electrode on the patch with a finger of the first hand and the fourth electrode on the patch with a finger of the second hand, wherein the reference ECG recording includes three orthogonal or quasi-orthogonal leads generated from the first electrode, the second electrode, the third electrode, and the fourth electrode;

recording a symptomatic ECG recording when a patient indicates the presence of symptoms on the patch, wherein the symptomatic ECG recording includes three orthogonal or quasi-orthogonal leads generated from the first electrode, the second electrode, the third electrode, and the fourth electrode; and

The symptomatic ECG is displayed superimposed with the reference ECG.

13. The method of claim 12, further comprising automatically detecting irregular cardiac signals from the symptomatic ECG recording using the reference ECG.

14. The method of claim 12, wherein the patient indicates the presence of symptoms on the patch by activating a button on the patch.

15. The method of claim 12, wherein the patient indicates the absence of symptoms on the patch by activating a button on the patch.

16. The method of claim 12, wherein the patient indicates the absence of symptoms on the patch by not activating a button on the patch indicating the presence of symptoms.

17. The method of claim 12, wherein acquiring the reference ECG includes processing bioelectrical signals from the first electrode, the second electrode, the third electrode, and the fourth electrode using a processing network to form the three orthogonal leads, the processing network forming a center point of transfer between the third electrode and the fourth electrode in a sagittal plane passing through the patient's chest while the patch remains adhesively secured to the patient's chest, wherein three orthogonal cardiac leads are formed by the electrodes and the center point.

18. The method of claim 12, wherein updating the reference ECG includes detecting finger contact on both the third electrode and the fourth electrode using a detection circuit.

19. An adhesive patch apparatus for synthesizing a 12-lead Electrocardiogram (ECG), the apparatus comprising:

an adhesive material patch having a back side and a front side, wherein the back side is configured to be adhesively secured to a chest of a patient;

a first electrode and a second electrode integrated on the back of the patch configured to measure bioelectrical signals from the chest of a patient, wherein the first electrode and the second electrode are positioned at a distance of at least 5cm apart;

a third electrode on the front face of the patch and configured to measure a bioelectric signal from the right hand of the patient;

a fourth electrode on the front face of the patch and configured to measure bioelectric signals from the left hand of the patient;

a processor within the housing of the patch configured to derive three orthogonal cardiac leads from the first electrode, the second electrode, the third electrode, and the fourth electrode; and

A detection circuit configured to detect finger contact on both the third electrode and the fourth electrode, further wherein the processor is configured to collect the three orthogonal leads when the detection circuit detects finger contact on both the third electrode and the fourth electrode.

20. The device of claim 19, further comprising a communication circuit within the housing configured to transmit the processed three orthogonal cardiac leads to a remote processor.

21. The apparatus of claim 19, further comprising a marker on the housing, the marker indicating an orientation of the patch when applied to a chest of a patient.

22. The apparatus of claim 19, further comprising an LED on the housing, the LED indicating an orientation of the housing.

23. The apparatus of claim 19, wherein the third and fourth electrodes are disposed on opposite sides with respect to a longitudinal plane of symmetry of the housing, the longitudinal plane of symmetry being substantially perpendicular to the back face of the housing.

24. The apparatus of claim 19, further comprising a ground electrode on the housing for contacting one hand of a patient, the ground electrode being disposed on a side or front of the housing.

25. The apparatus of claim 19, wherein the third electrode or the fourth electrode is ribbon-shaped and disposed along a first side of the housing.

26. The device of claim 19, wherein the processor is configured to automatically detect single lead ECG signals from the first and second electrodes when the detection circuit does not detect finger contact on both the third and fourth electrodes.

27. The device of claim 26, wherein the processor is configured to detect an irregular heart signal from the single lead ECG signal and, upon detection of the irregular heart signal, prompt the patient to touch the third and fourth electrodes.

28. The device of claim 19, further comprising a symptom presence input on the patch, wherein the processor is configured such that the three orthogonal cardiac leads derived from the first electrode, the second electrode, the third electrode, and the fourth electrode are marked with a flag indicating that the symptom presence input has been activated by a patient.