EP1152689A1 - Method of noninvasively determining a patient's susceptibility to arrhythmia - Google Patents

Abstract

A system and method for detecting a patient's susceptibility to arrhythmias and cardiac tissue abnormality is disclosed. The method consists of using a computer (27), a display (23), software (not shown) loaded into the computer (27) that generates graphical user interfaces (GUI), an electronic interface (18), and a plurality of electrodes (not numbered). The electronics interface (18) is in electronic communication with the computer (27), and further in electronic communication with the electrodes (not numbered) that are placed by self-adhesion at predetermined locations on a test subject (35). According to one aspect of the invention, the method enables a user, typically a medical professional, to initiate, with minimal input, certain diagnostic tests involving observing, analyzing a series of QRS complexes, some of which are biased with a subpacing current, and others of which are unbiased. The signals are then compared, and the differences are analyzed to detect a patient's susceptibility to arrhythmias, and cardiac tissue abnormality.

Description

METHOD OF NONLNVASIVELY DETERMINING A PATIENT'S SUSCEPTIBILITY TO ARRHYTHMIA

FTF.T .n OF INVFNTTON The invention relates to the detection of patients' susceptibility to arrhythmias and, more particularly, to various techniques for improving the detection of signals to achieve this goal.

R ACKOR I 1ND OF THF. INVENTION There are various devices known in the art for monitoring heart function. Many of these devices typically function by analyzing signals such as an electrocardiogram signal, which can be representative of heart function. There is a need to identify patients at high risk for life-threatening arrhythmias.

Various means have been proposed for detecting patient susceptibility to arrhythmias. United States Patent No. 5,1 17,834 discloses one method by which pulses of electromagnetic energy are injected into a patient and the changes in the patient's electrocardiographic signals caused by the injection are recorded. U. S. Patent No.

5,351 ,687 is similar in concept to U.S. Patent No. 5, 1 17,834, but it describes use of a magnetic sensor for use in detecting the cardiographic signals. U. S Patent No. 5,555,888 discloses various means for adapting and automatically facilitating the assessment techniques and means similar to that shown in the above patents for determining patient susceptibility to arrhythmias.

Other techniques which are used to analyze cardiac signals for somewhat similar purposes include those known as t-wave alternans and signal-averaged electrocardiograms. Each of these techniques is limited in its application and utility by various factors which are overcome through use of the below described inventions.

SUMMARY OF THF. INVENTION The present invention provides a system and method of determining, through noninvasive means, a patient's susceptibility to arrhythmia. More specifically, this invention comprises various improvements to known innovations for optimizing detection of a patient's susceptibility to arrhythmias. This invention embodies numerous software and sequence improvements for applying this basic technology.

Another purpose of this invention is to provide hardware and signal analysis means for detecting, amplifying, or improving recognition of relevant signals. Another purpose of this invention is to provide for improved performance lead sets and the software to promote ease of attachment and removal from the patient and ease of connection of the lead system to the hardware.

A further object of this invention is to provide new combinations of electrode placement and use to promote better arrhythmia susceptibility diagnosis. A further object of this invention is to provide a reduction in the size of necessary components to allow for hand-held system dimensions.

A further object of this invention is to provide a means for distinguishing between the signals from the X, Y, and Z directions as well as previously unused directional components of very low-level signal data. Another object of this invention is to supply means for displaying of patient's waveforms and other data derived from the detected signals, as well as to provide various interfaces to communicate the data between the patient and physician or health care professional.

It is a further object of this invention to provide signal artifact reduction, and to provide a single point connector for the set of leads.

Another object of this invention is to provide improved lead materials for improved performance, as well as an improved lead effect modeling (LEM).

It is yet another object of this invention to provide amplifier circuitry that minimizes amplifier saturation and optimizes fast recovery.

RRTF.F DESCRIPTIONS OF THF DR AWINGS Figure 1 depicts the broad overview of the invention, showing the patient electronic interface computer.

Figure 2 is an exemplary depiction of a patient showing possible electrode patient locations. Figure 3 is a more close-up view of the lead system, showing the connector and attached electrodes.

Figure 4 depicts the principal graphical user interface (GUI) generated by the computer and the software portion of the invention. 5 Figure 5 is the principal GUI generated by the computer and software portion of the invention, with the testing menu engaged. Figure 6 is the "New Subject" GUI. Figure 7 is the "Acquisition" GUI. Figure 8 is the "Perform All Standard Protocols" GUI. l o Figure 9 is the "Ready to Verify Sensing" GUI.

Figure 10 is the "Acquisition Active" GUI generated by the computer and software portion of the invention.

Figure 1 1 is the "Sensing Problem" GUI generated by the computer and software portion of the invention. 5 Figure 12 is the "Repeat Sensing Verification" GUI generated by the computer and software portion of the invention.

Figure 13 is the principal GUI generated by the computer and software portion of the invention, depicting a pulse graph.

Figure 14 is the "Ready to Begin Testing Execution" GUI generated by the 0 computer and software portion of the invention.

Figure 15 is the "Acquisition Active" GUI generated by the computer and software portion of the invention, depicting realtime R-wave acquisition.

Figure 16 is the "Halted Data Acquisition" GUI generated by the computer and software portion of the invention. 5 Figure 17 is the "Resume with Protocol" GUI generated by the computer and software portion of the invention.

Figure 18 is the principal GUI generated by the computer and software portion of the invention, depicting the "View" drop-down menu engaged.

Figure 19 is the "Options" GUI generated by the computer and software portion of 0 the invention. Figure 20 is the "Simulator" GUI generated by the computer and software portion of the invention.

Figure 21 is the "QRS Status" GUI generated by the computer and software portion of the invention. Figure 22 is the "Simulator" GUI generated by the computer and software portion of the invention, depicting a further display option.

Figure 23 is the "Simulator" GUI generated by the computer and software portion of the invention, depicting a further display option.

Figure 24 is the "Simulator" GUI generated by the computer and software portion of the invention.

Figure 25 is the "Simulator" GUI generated by the computer and software portion of the invention.

Figure 26 is the principal GUI generated by the computer and software portion of the invention, depicting the "Data" drop-down menu engaged. Figure 27 is the "Accessing Stored Subject Data" GUI generated by the computer and software portion of the invention.

Figure 28 is the "Open" GUI generated by the computer and software portion of the invention.

Figure 29 is the "Protocol Steps" GUI generated by the computer and software portion of the invention.

Figure 30 is the "Select Protocol Step" GUI generated by the computer and software portion of the invention.

Figure 31 is an exemplary EKG signal.

Figure 32 is a block diagram of switching and planting circuit of the electronic interface.

Figure 33 is a flow chart showing the overall interaction of the invention. Figure 34 is a more detailed view of the connector and attached leads, showing pin layout.

Figure 35 is a block diagram of the isolated driver and shunting switch, a portion of the electronics interface. Figure 36 is an exemplary series of QRS complexes.

Figure 37 is a high-level block diagram of the electronics interface.

Figure 38 is a wire-level depiction of the electronics interface.

Figure 39 is a flow chart/block diagram of the isolated fast recovery EKG amplifier.

Figure 40 is a schematic of the fast-recovery EKG amplifier.

Figure 41 is a block diagram/flow chart of the isolated driver section of the electronics interface.

Figure 42 is a schematic of the isolated driver section of the electronics interface. Figure 43 is a high-level flow chart of the operation of the software.

Figure 44 is a lower-level flow chart of the test control and acquisition portion of the software.

Figure 45 is a lower-level flow chart of the post-processing software operation.

Figure 46 is a lower-level flow chart of the realtime enter of controls implemented by the software.

Figure 47 is a data set of observed data.

Figure 48 is a data set of observed data.

Figure 49 is a data set of observed data.

Figure 50 is a data set of observed data. Figure 51 is a data set of observed data.

Figure 52 is a data set of observed data.

Figure 53 is a data set of observed data.

Figure 54 is a data set of observed data.

Figure 55 is a data set of observed data.

DF.TATI .FT) DESCRIPTION OF THF. PREFER RED EMBODIMENTS The invention provided is an improved method and system for detecting patients' susceptibility to arrhythmia and cardiac tissue abnormality in a noninvasive fashion. In Figure 1 , computer 27 is operably coupled to monitor 23, which is further closely coupled with electronic interface 18 via wire 31. Lead system 12 is connected between patient 35 and electronic interface 18.

Figure 2 is a front and rear view of patient 35. In one preferred embodiment, lead system 12 consists of 9 lead wires. Advantageously, the lead system can be connected as shown in Figure 2 for efficient and consistent setup of the invention. Typically, the lead system is preassembled with a predetermined number of leads having predetermined lengths. Although it is contemplated by this invention that the lead system can be preassembled with leads of different lengths to accommodate different room sizes and patent locations, among other factors, a general consideration is that the sensing leads and energy delivery leads are less than 9 feet in length to reduce possible induced noise. Further, the leads in lead system 12 are constructed from a low-impedance material, such as tin, sodium, silver, silver chloride, or other low-impedance material recognized as such by those skilled in the art. This construction assists in efficient delivery of subpacing energy for stimulation leads and increased sensitivity for sensing leads. The electrodes involved with energy delivery are advantageously shaped and sized for placement on the patient's body habitus to minimize signal quality reduction by avoiding muscle tissue.

Figure 3 shows a more detailed view of one preferred embodiment of single-point connector 15 with 9 lead wires electronically coupled thereto. In this embodiment, each of the 9 lead wires is connected to one of 9 self-adhesive electrodes. The adhesive used on any specific electrode can differ depending on various factors, including where on patient 35 the electrode or patch is to be affixed and whether the electrode is reusable or disposable. In one preferred embodiment, electrode 1 is to be connected in the correspondingly-numbered position indicated in Figure 2. Thus, for example, electrodes 1 and 2 are connected on patient 35 at the corresponding left and right mid-axillary lines, on a horizontal plane, at the level where the fifth intercostal space intersects the sternum. Electrode 3 is placed on the sternum. In this embodiment of the invention, electrode 4 is placed on patient 35 at the fifth intercostal space. Electrode 5 is a neck electrode and is attached generally at the back of the neck, as indicated on back view 2.2 of Figure 2. Lead 6 is a left leg lead that will attach generally in the location on patient 35, as shown on front view 2.1 of Figure 2. The larger, rectangular electrodes, electrodes 7 and 8, are attached in the pectoral area and back, respectively, as shown in Figure 2. In one preferred embodiment, the generally pectorally-placed electrode 7 or patch has a skin contact surface area of at least 20 cm², and typically less than about 70 cm². The patches of lead system 12 can be constructed with different electrical characteristics to facilitate energy transfer and sensing. Single-point connector 15 is configured to electronically mate with electronic interface 18. A top-level block diagram of electronic interface 18 is shown in Figure 37. In one embodiment, single-point connector 15 advantageously couples 9 electroleads into one plug assembly. As can be seen in Figure 3, one preferred embodiment is a stacked lead receptacle having at least two rows of lead connections that are identified with respect to each lead (also see Figure 42). This advantageously provides for a more compact connector, and provides for rapid and efficient coupling and decoupling to electronics interface 18. In one preferred embodiment, the connector 15 is designed to be easily and rapidly coupled and decoupled with the electronics interface 18 by the use of only one hand. Advantageously, this allows for efficient setup and takedown of the invention. Patches 1 through 9 are premarked, as indicated on Figure 3, to provide for simpler and more convenient placement on patient 35. Further, the lead system 12 comprises a reference lead 9. It is anticipated that the lead system 12 can be a single-use system or a disposable system to provide for a safe and sterile means by which to perform the tests provided by this invention. Further, reusing the lead system may create a higher impedance in the system, which may make the lead system 12 more susceptible to noise. In one preferred embodiment of the invention, a means is provided for determining whether the lead system has been previously used. This can be done by using a single-use-type adhesive. Another means for detecting previous use is creating a deformable tab on connector 15 that deforms on its first mating with electronic interface 18, and thereafter is not usable. Creating fusible links or breakable tabs to indicate the lead system has been previously used are an additional means, among others.

The electronics interface 18, by coupling with computer 27, allows for the injection of low-level electromagnetic energy into patient 35 to alter at least one cardiac signal. The energy is delivered at a subpacing threshold and is typically introduced externally, through patient 35's chest and into cardiac tissue. The subpacing energy is delivered just before a QRS complex event, as determined by the data gathered by the hardware and electronic interface 18, and as analyzed by the software. Electronic interface 18 and attached computer 27 function to process received signals, among other functions. The energy delivery leads are typically leads 7 and 8; however, it is anticipated that circumstances may arise where more or less than two energy delivery leads may be needed. In such cases, greater or fewer leads may be configured to delivery energy. Further, the number of sensing leads may be variable as well, depending on the needs and judgment of the medical professional administering the testing.

Figure 31 depicts an exemplary QRS complex and related signals. P-wave 153 is the signal that typically precedes the actual QRS complex 130. The interval between the start of the P-wave and the beginning of QRS complex 130 is known as the PR interval 150. QRS complex 130 is typically made up of three distinct components: Q 1 17, which is typically the first negative signal; R 1 13, which is typically the first positive signal; and S 121 , which is the first negative signal subsequent to R 1 13 signal. T segment 133 is typically defined as the more-or-less flat signal, or absence of signal, subsequent to recovery of the S 121 portion of QRS complex 130, prior to commencement of t-wave 146. The QT interval is typically defined as the portion of the signals commencing at the beginning of QRS complex 130 and ending after t-wave 146. J Joint 137 is typically defined as the end of the QRS complex and the beginning of the ST segment 133. The T-P interval (not indicated) is the time period from the end of the T-wave to the beginning of the next P-Wave. The entire cardiac cycle is P-Q-R-S-T.

The slight transcutaneous biosync or subpacing current is typically introduced by the invention at odd numbers of QRS complex normal sinus beats. Resulting QRS complexes are then compared to the even-numbered unbiased beats. By computer-implemented software, the distinguishable signal differences can then be calculated and displayed. Generally, differences are found between the biased and unbiased QRS complexes in patients with ventricular tachycardia and other indices of arrhythmia or cardiac tissue abnormality. It is anticipated that these input potentials would be extremely small, for example, less than lOOuV, and typically of a duration of less than about 100 mS. Such a current might involve visualization of a possible analog of late potentials throughout the QRS complex.

Computer 27 operates a graphical user interface (GUI) based software, which generally includes a tool bar, a status bar, a display area, and various drop-down menus. The principal GUI is depicted in Figure 4. The GUI consists of display area 39, status bar 37, tool bar 42, and drop-down menus 46. Tool bar 42 contains button icons that represent shortcuts to many of the functions described below in association with drop-down means 46. Status bar 37 depicts the general status 13 of the software on the left-hand side, technical data 10 regarding the lead sensors and input current in the middle section, and frequency and protocol information 28 generally on the right-hand side. Figure 4 illustrates a GUI in Microsoft Corporation's Windows 95rj operating system format. The GUI is generated by computer 27, which typically consists of mouse 40, CPU 25, display 23, a keyboard (not shown) operably attached to computer 27, and peripheral input/output devices 26, as well as storage media 21.

Figure 5 depicts "Testing" drop-down menu 48 engaged. As revealed in Figure 5, "Testing" drop-down menu 48 provides a series of options to perform testing provided for by this invention. If the "Performed Test Sequence" 50 is selected, the GUI of Figure 6 is generated on display 23. Using mouse 40 or keyboard input, a preexisting patient may be selected from display area 39 of this GUI, or "New Patient" button 52 may be selected. Mouse 40 or keyboard input may be used to select all operable functions of the GUIs involved in this invention. If "OK" 36 is selected from the GUI of Figure 36, subject information 41 is retrieved for the highlighted subject. "Cancel" 30 returns the operator to the view of the GUI of Figure 4.

Figure 7 depicts the informational GUI that appears if "New Patient" button 52 is selected. In the upper portion of the GUI represented in Figure 7, subject information may be entered in box 44 which includes identification number (ID) 55 to associate with the patient, patient's Name 58, patient's Birthdate 64, Gender 66 of the patient, Race 80 of the patient, and any miscellaneous notes 85 that might be helpful during or after the patient's diagnostic sessions.

The lower portion of the GUI depicted in Figure 7 includes six boxes where testing parameters are entered. The test duration box 90 is configured by the medical professional to indicate how many QRS complex signals will comprise the test. The options under the sensitivity input box 68 are low, medium, and high. This advantageously allows the sensitivity to be adjusted to correct over- or under-sensing caused by subject-to-subject variation in QRS amplitude and morphology. The next variable parameter is the deviation limit 87, which is entered in milliseconds in the correspondingly marked box. Deviation limit 87 allows the operator to eliminate inaccurately-positioned stimulations from post-processing. This can happen due to the predictive nature of pre-R-wave stimulation and the normal R-R interval variation (see Figure 36). The operator identifies the allowable tolerance. Any pulses that are greater than this tolerance are eliminated from further processing. Also in Figure 7 is pulse configuration box 33. In pulse configuration box 33, the low-current pulse can be configured to account for the different circumstances of the patient to be tested. The parameters or variables are current strength 72, width of the pulse 82 (in milliseconds), and temporal location 92 of the pulse with respect to the QRS complex. A one-millisecond Pulse Ramp Up 78 option is also available by checking the corresponding box on the GUI.

Figure 8 depicts a GUI option screen where a simplified selection can be made for all available testing standard protocols. There, selection of "Yes" 1 1 invokes all currently defined standard protocols. These protocols are set up initially and invoke from this screen. This option advantageously allows testing without requiring the operator to set the specific parameters for each subject being tested. "No" 17 returns the user to the previously displayed GUI.

Figure 9 is a GUI that appears on screen 23 to determine whether the professional is ready to verify the sensing of the electrodes attached to patient 35. "Yes" 36 will commence the sensor verification. "Cancel" 30 will return the operator to the previous screen. If default protocols are to be used on the patient, then the operator need not define the test parameters. The system will get these standard parameters from the internal disk (not shown) of computer 27.

If "Cancel" 30 is selected on the GUI of Figure 7, any changes will be discarded and the performed test function will cease. If "OK" 36 is selected on the GUI of Figure 7, the GUI of Figure 8 will appear. The medical professional will select "Yes" 1 1 if the system is to use the standard protocol stored internally.

In a particular embodiment of the subject invention, prior to acquiring test data for a particular test, the computer-implemented software will acquire data for a 10-second interval, displaying and indicating detected R- waves or QRS complexes (see Figure 31). This process allows the operator to confirm the placement of lead system 12, and the sensitivity settings that appear in the GUI of Figure 7. If the test data is not completely satisfactory to the operator, the steps represented in Figures 7, 8, 9, and 10 may be iterated to allow the medical professional to reposition the leads, if necessary, to provide for optimal sensing and signal amplitude. During data acquisition, a window depicting the data being acquired appears. An exemplary display of this graphical depiction of acquired signal 47 appears in Figure 10. After the typical 10-second acquisition time, the GUI of Figure 1 1 or Figure 12 may appear. The GUI of Figure 12 gives the operator the opportunity for another approximately 10-second data acquisition period. If software-detected problems occur during data acquisition, a GUI such as the one displayed in Figure 1 1 may appear, notifying the operator of potential problems. These features give the operator more control over the testing procedure, and advantageously provide for error control.

Typically, in one preferred embodiment of the invention, an auditory beeping occurs with R-wave acquisition. If no R-wave beeping occurs or if poor signal amplitude is noted, adjustments in the leads may again be required, and sensing verification should be repeated via the GUI of Figure 12.

In situations where the operator is not performing standard protocols, the system will allow the operator to interactively set the pulse position. Figure 13 is a graphical depiction of pulse 59 on display area 39. Under these circumstances, the operator may use the cursor keys on the keyboard (not shown), coupled to computer 27 (not shown in Figure 13), to position the pulse location using an average of the QRS complex signals received during sensing verification.

In one preferred embodiment, the final step in the performance of the test sequence function involves performing and recording the test. Prior to performing and recording the test, the software will represent the GUI prompt of Figure 14. This will allow the operator to control the timing of the test to ensure that both patient 35 and the operator are ready to proceed.

When the "OK" 36 selection is made from the GUI of Figure 14, the GUI of Figure 15 is generated, graphically depicting the R-wave 34 in real time. If "Cancel" 30 is selected, the operator is returned to the previous screen. The system is configured to emit an audible beep synchronously with each R-wave sensed. As indicated on the GUI of Figure 15, pressing any key of the computer keyboard will halt the performance test sequence. If a key is depressed during the test sequence, the GUI notification screen of Figure 16 appears, notifying the operator what has occurred.

This invention anticipates that several other events may occur that would halt acquisition, and similar GUIs to the GUI depicted in Figure 16 will report such termination of the test procedure. For example, if R-wave sensing is indicated at a rate greater than 180 beats per minute, the test will automatically be halted. Further, if the invention is having difficulty sensing the R-wave, or the R-wave is in any way irregular, the test will be halted. If the test is interrupted during the execution of a test sequence, the sequence may be restarted at the beginning of the interrupted test by selecting "Yes" 1 1 from the GUI notification screen of Figure 17, which will be displayed after the test sequence is halted. Selecting "No" 17 from the GUI of Figure 17 causes the system to return to the main menu screen of Figure 4. If any of the remaining menu items in drop-down menu 48 are selected, a shortcut to a previously-described procedure is executed. If "Quit" 19 (see Figure 5) from Testing drop-down menu 48 is selected, the software program is closed.

Figure 18 shows the View drop-down menu 55 engaged. View drop-down menu 55 provides access to functions required to select viewing options for data acquired or loaded from disk. Each test performed by the subject of the invention records 3 channels of data. The placement of electrodes (see Figure 2) allows these signals to record far-field ECG in roughly orthogonal directions. It is recognized that the terms "ECG" and "ECG data" encompass electrocardiograms and similar data measured, generated, or reported by all means, including by use of the devices and methods disclosed herein. Referring again to the electrode placement, this advantageously provides for a data representation that defines the signal in three dimensions. Axes have been labeled X, Y, and Z. The X signal is recorded, for example, from left lead 1 to right lead 2, with left lead 1 being the positive direction. The Y signal may be recorded from neck lead 5 to leg lead 6, with neck lead 5 being the positive direction. The Z signal may be recorded from back lead 4 to sternum lead 3, with back lead 4 being the positive direction. Other configurations may be possible, depending upon the judgment and needs of the patient and operator. In addition to the three required signals, at least two additional signals are preferably calculated. The X, Y, and Z signals are combined to produce a magnitude and direction signal. A magnitude signal can be used to detect signal variation independent of direction. A direction signal can be used to detect signal variation independent of magnitude. The upper portion of View drop-down menu 55 contains selectable options for each of the signals X 100, Y 102, and Z 104. The options appear checked on the GUI when they are selected. These selections allow the medical professional to select which signals are displayed during certain viewing modes. The lower portion of the pull-down menu contains the viewing modes. Each mode allows the user to view the current data set in a different way. The viewing modes, as they appear on drop-down menu 55, are "View Full Resolution," 1 19, which displays the X, Y, and Z signals at high resolution on monitor 23; "View 2 Minute Screen" 123, which displays a selected signal compressed into two minutes per screen; and "View QRS Change" 125, which displays the selected signals with normal average, biased average, and difference depictions. Selection of "Vector Angle" 139 displays the angular velocity and direction change of the average signal. "Position Bias Pulse" 1 1 1 displays the average of the selected signals, along with an indicator of pulse position. This advantageously allows interactive positioning of stimulation by the medical professional performing the diagnostics.

"Signal Averaged ECG" 135 displays signal-averaged ECG information for normal, biased, and difference signals. Typically, in the application of signal-averaged ECG 135, of primary importance to the medical professional is the flat area immediately following the QRS complex, ST segment 133. ST Segment 133 is targeted because of its lack of signal in normal people (see Figure 31). This lack of signal allows the recognition of the presence of very small-amplitude signals that can occur in people with conduction problems indicative of a susceptibility to arrhythmia or other cardiac tissue abnormality. Further, abnormal signals may also exist within the QRS and be masked by the higher-amplitude signal present there. Since this invention has the ability to perform comparative analysis between stimulated and non-stimulated beats, a much greater sensitivity may be achieved in areas where a higher natural signal is also present. Additionally, by examining various areas of the QRS complex, information regarding size and position of conduction alteration may also be evident.

If "Options" 128 menu selection is made from View drop-down menu 55, the GUI of Figure 19 is displayed. "Option" 128, which is selectable by the GUI, is represented in Figure 19. This function allows for better interpretation of the data accumulated. The "High-Pass Cutoff option 60 of the GUI in Figure 19 can be set to use a fast-fourier transform (FFT), to filter out frequencies lower than those indicated prior to averaging. A zero setting disables high-pass filtering altogether. Low-pass cutoff 94 uses an FFT to filter out frequencies higher than those indicated prior to averaging. A setting of 1,000 disables low-pass filtering. Advantageously, lead effective modeling (LEM) can be selected in the GUI represented in Figure 19. If LEM box 96 is checked, in a preferred embodiment, a 20-millisecond model of the impulse artifact is constructed, based on the first four simulations. This model is subtracted from subsequent simulations to reduce artifact in the displayed information. Any voltage shifts created during stimulation are also modeled and removed. LEM and this correction algorithm greatly reduce artifact created by stimulation. A muscle response correction algorithm may also be implemented by the invention to advantageously correct for signal artifacts during stimulation and acquisition cycles. Using this technique stimulation is provided to the patient within an LEM time period between the T and P waves, at the beginning and periodically throughout the stimulation and acquisition process. Response to the stimulations is determined up to about 50 milliseconds for each stimulation. LEM is then created by combining the response of the stimulations during this period to generate a response signal, whereafter the signal is used to mathematically attribute noise generated by electrical artifact and muscle activity. Also GUI selectable is a "60-Hz Notch FFT Filtering" 86 option, which advantageously filters out frequencies at the 60-Hz rate prior to averaging. Accumulation Start time 88 and End time 89 can also be input on the GUI indicated in Figure 19. Accumulation Start time 88 controls the starting range for the accumulated difference measurement on the average screen. The Accumulation End setting 89 controls the ending range for the accumulated difference on the average screen. An exemplary result of selecting "View Full Resolution" mode 1 19 is depicted in Figure 20. Signal characteristics X 167, Y 173, and Z 177 are graphed independently. Again, status bar 37 indicates the various selected parameters previously discussed.

Individual QRS status may be determined from the GUI of Figure 21. The various options in the QRS Status window 97 are as follows: if the status indicated is "Biased," that means that the QRS complex has a stimulation associated with it. If it is "Normal," the QRS does not have an associated stimulation. The parameter "Valid" in status window 97 means that the QRS has past selection criteria which is included in the averaging. If the LEM stimulation is indicated (not shown), this means that the QRS complex is used for LEM. If "low correlation" is indicated (not shown) in status window 97, the QRS complex was too low and, therefore, was not used in the averaging. If there is a "Bad Interval" indication (not shown), then the preceding or following interval changed by greater than 300 milliseconds. If a "high-rate" status indication is indicated (not shown), the pulse rate exceeded 180 beats per minute and the QRS complex was not used in the averaging. If "manual exclusion" is indicated (not shown), that means that the QRS complex was manually excluded by the operator. If "Bad pulse Positioning" is indicated (not shown), the pulse position exceeded the tolerance set by the medical professional or the default tolerance. Further, it is possible to manually include or exclude a particular QRS from the averaging statistics by using the "Include" 162 and "Exclude" 168 selection buttons on the GUI of Figure 21. A previous QRS complex may be viewed by selecting the "prior QRS" button 142. The next QRS complex can be viewed by the selection of the "Next QRS" button 143.

An exemplary result of selecting "View 2 Minute Screen" 123 is depicted in Figure 22. The 2 Minute Screen mode allows the medical professional to view a selected channel in an overview mode. In this mode, a two-minute portion of the selected channel 138 is displayed on display area 39. R-wave correlation points and stimulation points are indicated on the display area of Figure 20. R-wave correlation points are longer, white indications (not shown) above the waveform. Stimulation points are red indications (now shown) below the waveform. Note that both Full Resolution 1 19 and View 2 Minute Screen 123 modes display the current start and end time for the displayed portion of the test on status bar 37 at the bottom of the relevant GUI. Advantageously, as the operator scrolls through the data, these values change to indicate the portion of data currently being displayed.

An exemplary result of selecting "View QRS Change" 125 mode is depicted in Figure 23. In Figure 23, the upper graph 61 shows the average of all nonbiased QRS complexes. The middle graph 65 shows the average of all biased or stimulated QRS complexes. The lower graph 67 is the difference graph that shows the difference between the normal and biased waveforms. Statistics identifying the accumulated area under each curve are displayed on the right. A double-end arrow 33 on the lower graph indicates the range over which the statistics were generated. The end points can be adjusted in the view options window. The Difference graph contains cumulative Difference results along the bottom of each 10-millisecond region, based on the magnitude signal. Figure 24 depicts the Vector Angle GUI. Vector Angle mode displays angular information 151 not reflected in the magnitude signal. The Vector angle mode displays changes in the direction of the electrical signal, whereas the Magnitude mode displays changes in the amount of electrical signal.

When the Signal Averaged ECG menu selection is made from View drop-down menu 55, the GUI of Figure 25 is displayed on computer screen 23. The various graphs represent the Signal Averaged information for the Normal 43 and Biased 44 QRS complexes, along with the Difference 45 between the two. Standard QRS, LAS 40 and RMS 40 calculations can be made. Noise threshold is displayed along with the standard deviation of the noise, as can be seen on the GUI of Figure 25.

Another drop-down menu 46 is the Data drop-down menu 58. Data drop-down menu 58 provides access to functions required for loading previously acquired data from storage, such as a hard disk located in computer 27, or from removable storage, such as a ZipD disk or other removable storage media. Configuration of protocol steps is also supported here, along with typical backup and restore functions.

Figure 27 is a GUI depiction of an exemplary menu for stored data. The date 16 and time 20 of acquisition, the identification 38, name 32, age 53, gender 54, bias information 63, R-wave sensitivity, and valid count 71 are all identified for reference, as can be noted in the upper area 14 as depicted in Figure 27. Selecting "Load From Internal Disk" option 126 from drop-down menu 58 reveals the GUI depicted in Figure 28. The GUI of Figure 28 depicts a variety of test data 57 that can be selected.

If "Load Protocol Step" 131 is selected from the drop-down menu, the GUI of Figure 29 is displayed. This function loads an identified protocol step 69 into the current test configuration. The GUI dialog box allows the operator to identify the protocol step to load. Current patient information is not changed. To select a test configuration as a protocol step, the GUI of Figure 30 is used. The protocol step is entered into "Select Protocol Step" window 158 of the GUI, and "OK" 36 is selected to save the step. Selection of "Restore" 1 14 from Data drop-down menu 58 restores data from an external media, such as a Zipr disk, back to the internal hard drive of computer 27. Further, using the "Export" 195 command, data can be exported to certain spreadsheet software programs.

The "Append To Stats" option 163 can be selected to append the statistics of the current configuration parameters to the file. Advantageously, this option allows all test data sets in the current drive and directory to be processed using the current processing parameters and appended to the selected text, or .TXT, file. This useful option allows for batch processing and results based on altered settings.

Another menu 46 is Help drop-down menu 60. Full index and search capabilities of Help information is available. Further, on-line help, such as information gatherable through the Internet, is also anticipated.

A high-level operator flow chart for the software described above appears in Figure 43. A typical embodiment of the method of using the software begins at the Attach Leads To Patient stage 280. As described above, the operator will then Invoke Testing 282 and Input Patient Information 284. If only a single test is desired, path 287 is taken, wherein the operator has a chance to Define Test Parameters 291. Otherwise, the operator has the choice of selecting All Tests Desired 289 and proceeding directly to Verify Sensing 293. If Verify Sensing 293 is Bad 295, then the lead positioning can be adjusted 297, and the verified sensing retried 294. Once the sensing is Good 198, the test parameters are loaded and the test is performed 288. Once the test is completed 292, there is a chance for the operator to see if more tests need to be performed 296. If "Yes" 290, then the next predefined tests are loaded 286, and the operator is returned to Test Parameters Loaded and Test is Performed 288. If no further tests are to be formed at the 296 state, the "No" path 299 is selected and the test is completed and leads are disconnected 300.

Figure 44 is a depiction of the test control and data acquisition software flow chart. Raw data received from lead system 12 is received at the Realtime Test Control and Monitor Software 310, along with Realtime R-Wave Indicators 306. Realtime Test Control and Monitor Software 310 then controls and relays this information to generate GUIs to make a realtime display 312 on monitor 23. Inputs from the control system can control other test features, as well, such as User Abort Control 304 and the user's ability to perform Test Configuration 308. Realtime Test Control and Monitor Software 310 can also send the Raw Data 303 to storage 313, and save Subject & Test Information 315. Figure 45 depicts the software flow charts of the post-processing software. Annotation and post-processing control 332 controls View Options 325 as described above, and subject and test information retrieval from storage 320. Raw data from storage 326 is retrieved and analyzed for R-wave detection 332. If LEM generation 330 is requested, then LEM Correction 334 will be performed, and Correlated QRS Alignment 336 performed. Then, one to typically four processing options may be selected. Average Processing 340 can be selected for the data to be analyzed after being filtered through filtering process 338. Then the options of displaying 350 or saving 355 the data are available. If variance processing 342 is selected, the results may be displayed 350 or saved 355. Similarly, if Power Spectrum Processing 344 is selected, the results may be displayed 350 and/or saved 355. Also, Direction Vector Processing 346 may be selected and, again, the resulting information can be displayed 350 and/or saved 355. Figure 46 displays the lower-level flow diagram, more particularly, the stimulation timing software and the switch, shunt, relay, and stimulation control features that allow for efficient subpacing stimulation signals to be timely and efficiently administered, as well as to facilitate the ability of the invention to make fast recovery to prepare for the next QRS complex event. Raw Data Stream 370 is filtered by Filters 368 and is sent to Realtime LEM Generator 360, and any realtime LEM correction is made at 366. Realtime R-wave detection is determined at step 364; and, if detected, the realtime r-wave indications are passed on at 362. Realtime R-Wave Detection 364 is also linked with the Stimulation Timing Software 352 that determines the timing of the subpacing electrical pulse. Stimulation Timing Software 352 interacts with the switch on the relay and the stimulation control portion of the software 358. The computer interconnects to the electronic interface as shown at 372.

Figure 36 depicts an exemplary series of QRS complexes 130, or R-wave events. As can be seen, interval 144 is defined by that interval from the beginning of one QRS complex to the beginning of the next QRS complex. During the testing provided by this invention, a Pulse-Delivery Point 1 10 is determined by the invention, and a subpacing current is delivered, typically as shown in Figure 36. There is then the anticipated R-wave 1 15, based upon two previous R-waves. In one preferred embodiment, the response to the stimulation is determined for a period of up to about 50 ms after the stimulation. Any change in the characteristics of the QRS complex 130 following delivery of the subpacing pulse at delivery point 1 10 can be used in the diagnosis of a patient's susceptibility for arrythmia and cardiac tissue abnormality. A desired pulse position with respect to a detected R-wave is configured by the operator. When the intended position and time with respect to a detected R-wave is at or following the R-wave, then the device delivers a pulse after an appropriate-length delay following the most recently detected R-wave. When the intended position and time with respect to a detected R-wave are before the R-wave, then the device uses the previous R-interval 144 to determine an estimated time for delay by subtracting the desired amount from the R to R interval 144. The device then delivers the pulse after the determined delay following the most recently detected R-wave. The computer software is controlled with simulation and data acquisition during testing. During each test, the software delivers stimulation to alternating QRS complexes, based on realtime R-wave detection. Signals are recorded from lead system 12, along with the stimulation and R-wave detection locations. This is monitored and is terminated when the appropriate number of pulses have been delivered in the region identified in the test parameters.

Another process for arrythmia detection is that of t-wave alternan analysis. This process involves looking for alternations from beat to beat in the signal produced during the t-wave portion of the heart signal. The t-wave is the portion of the heart signal that follows the QRS "contraction" (see Figure 31) of the heart. The QRS area is called depolarization. The t-wave is called repolarization because the cells are electrically preparing for the next depolarization. T-wave analysis involves computing the 'power' of each t-wave and looking for alternations in this power from beat to beat. This phenomenon tends to increase in people prone to arrhythmia. The use of t-wave alternan analysis with the previously-described technique of subthreshold stimulation is anticipated by this invention.

An overview of the operation of this invention can be seen in Figure 33. Sensing Leads 202 pass received Signals 248 to the fast-recovery amplifier, at which time the Signals 248 are passed to the Analog to Digital converter 208. Thereafter, Data 250 is used to determine R-wave Detection 237 and for LEM modeling 215. Data 250 is also capable of going to Storage 218, and is further used for Post-Processing 240, where data 250 is eventually displayed to computer monitor 23. During the fast-recovery amplifier stage 254, Blanking Control 212, through Control 253, is used to compensate for blanking. This blanking control is initiated through the Software and Hardware Control Logic 234 via Control 253. Control 259 controls the R-wave detection 235 as it is passed to the Software and Hardware Control Logic 234. Software and Hardware Control Logic 234 further controls a Shunt Control 225 via Control 254; and Control 257 controls Current Controlled Driver 221. Hardware and Software Control Logic 234 passes Data 250 to the Digital to Analog Conversion 228, thereafter passing those Signals 255 to the Current Controlled Driver 221. At the appropriate time, Signal 255 is delivered to Stimulation Leads 206. Post-Processing 240 also performs LEM modeling 215, Digital Filtering 243, and Statistical Calculations 246, described in more detail below.

A significant part of the subject invention is the amplifier and driver circuitry located in electronic interface 18. Electronic interface 18 provides amplification of signals received from lead system 12 and amplifies those signals to a level of impedance readable by the computerized data acquisition/control system, such as computer 27. Electronic interface 18 also takes control signals from the computerized data acquisition/control system, such as computer 27, and provides stimulation into lead system 12, as described above. The amplifier circuitry is designed to record lead signals that occur immediately following the injection of energy into the lead system. The recording typically occurs within only several milliseconds of the injection of energy. Fast recovery is important to the system because of the need to sense electrical information very shortly after a stimulation. In one preferred embodiment shown in Figure 37, each vector X, Y, and Z has its own amplifier, X amplifier 155, Y amplifier 165, and Z amplifier 175. Stimulator 180 controls subpacing pulse delivery in conjunction with computer 27; and the software Power Conditioning Circuit 182 powers amplifiers 155, 165, and 175 supplying Stimulator 180 with subpacing current. Figure 38 is a wire-level diagram of Figure 37, illustrating this advantageous design.

To provide for such fast recovery, several methods are employed. The sensing leads are comprised of fast-recovery material, such as tin, sodium, silver and silver chloride, or other such material know to those skilled in the art, to facilitate rapid dissipation of any energy induced by the system. Further, electronics interface 18 uses a multistage amplification scheme as known to those persons skilled in the implementation of amplifiers, with improvements for fast recovery. Figure 38 shows a wire-level block diagram of this embodiment of electronic interface 18. In one preferred embodiment, electronic switches are placed between amplification stages, which are used to decouple stages within the amplifier. The amplifier must be switched into its high-impedance mode, with appropriate time allowances for all electrical switching to be completed prior to the application of any energy to the stimulation leads. Similarly when switching back to normal impedance mode, appropriate timings must be used to ensure that all stimulation energy is completely terminated prior to lowering the amplifier impedance. This timing must account for any engaging or disengaging delay in both the amplifier and energy delivery circuits. When the amplifier is in its normal- or low-impedance mode, it has a capacity to store up charge in a very short period of time. Therefore, application of stimulation energy, however short, in this mode will greatly increase undesirable artifact. Therefore, timing is critical in decoupling the amplifier to reduce artifact.

Advantageously, switch timing is software-controlled in one preferred embodiment of this invention. Other timing means are known to those skilled in the art. Filtering is implemented by this invention to filter the acquired signal to eliminate possible high frequency, switch-related artifacts. An additional clamping circuit is also employed to aid in the reduced recovery time during stimulation. As can be seen in Figure 39, an electronic track and hold switch 160 is placed between two stages of the amplifier. Track and hold switch 160 remains closed during stimulation, and in a preferred embodiment, a blanking period following stimulation. Figure 39 is a block diagram/flow chart of the operation of the isolated fast-recovery EKG amplifier. Differential input signal 261 enters the Differential First Stage Amplifier Circuitry 264. Thereafter, it is controlled by Clamping Circuit 1 17. The signal is thereafter controlled by Clamping Circuit 1 17. The signal is then conditioned by Bandpass Gain Stage 267 and is regulated by Impedance Switching Track and Hold Circuitry 160. As depicted in Figure 39, Switch Control 277 and Switch Isolation circuitry 275 control the timing of the signal. At the appropriate time, signals pass to Low Pass circuitry 269 and then to Final Gain Stage 271 and Isolation Stage 273. Finally, the amplified signal leaves the fast-recovery EKG amplifier as Amplified Signal 278.

Figure 40 is a schematic of the fast-recovery EKG amplifier. Figure 40 depicts the circuitry implementing the flow chart of Figure 39. As can be seen, differential inputs 183 connect to the differential first-stage amplifier circuitry 187. The next stage is clamping circuitry 184, which is in electrical communication with the bandpass gain stage 185. Next are the switch-and-hold circuitry 181 , low-pass filter stage 189, and final gain stage 188. Isolated circuitry 186 and switching circuitry 181 are also depicted in Figure 40. Figure 32 is a block diagram of the switching circuit. A clamping circuit is also added within the preswitch stages. The clamping circuit is designed to engage when the input signal is greater than about plus or minus 5 mV. When switch 70 is closed, the circuit behaves as a typical amplifier, using the reference lead as a body surface reference point for amplification of the differential signal between the positive and negative leads. Advantageously, this reference point is utilized during periods of blanking of the input signals. The clamping circuit remains inactive for input signals of plus or minus 5 mV. This allows amplification of normal skin surface ECG signals. During stimulation, the switch electronically disengages the amplification stages from each other. While open, switch 70 itself provides a hold function that holds constant the signal level for all postswitch stages 74. Switch 70 also decouples the reference signal from the preswitch stage 77. This decoupling advantageously prevents the preswitch stage from accepting any transient energy present during stimulation. In addition to switch 70, clamping circuit 62 engages when the input signal of greater than plus or minus 5 mV occurs. This clamping circuit 62 uses reference lead 9 to measure a baseline. A baseline shift is caused by the remnant charge left in the patient's body following the stimulation, shunting and modeling cycles performed by a preferred embodiment of the invention. This remnant charge equalizes over time at an exponential rate referred to as baseline decay. Compensation for baseline effects can be done by subtracting a non-stimulated waveform from a stimulated wave form. Further, a baseline shift with a time constant decay may also be utilized. The decay rate may be modeled by sampling the decay rate over a predetermined interval, for example, about 10 ms. The decaying baseline shift can then be mathematically removed from the acquired data. Advantageously, the decaying baseline shift may be removed for predetermined intervals, for example, intervals up to about 300 ms. Baseline noise can advantageously be reduced by filtering and statistical noise reduction by this invention, Whenever the input signal deviates from this baseline by more than 5 mV, the internal amplification stage is held at that level. This further reduces the effect of transient voltages generated during stimulation. These two features work together to keep the amplifier stages as close as possible to their prestimulation values, advantageously providing a very fast recovery time. An additional circuit in postswitch stage 74 provides a filter that eliminates any possible high-frequency, switch-related artifact that may occur. This is required because of the nature of the switch employed. This recovery technique is incorporated within the amplifier in one preferred embodiment of this invention. Figure 41 is a flow chart block diagram of the isolated driver section of the subject invention. This is additional circuitry located within electronic interface 18. This driver section depicted in Figure 41 has the characteristics to shape the energy delivery pulse to reduce rise-and-fall slopes, thereby reducing induced artifact signals. Further, the isolated driver depicted in Figure 41 provides for shunting of any charges built up as a result of energy delivery. Shunting means may include switching from a high-impedance path to a low-impedance path for a short period of time to dissipate unwanted voltage that is present. The switching between high and low impedances is designed to occur within a time of less than 1 ms. Typically, high impedance is greater than about 5,000 Ohms, and low impedance is less than about 500 Ohms. This shunting means can be connected between more than one energy delivery lead. Further, the driver employs a constant current circuit, thereby allowing control over energy delivery and varying lead or physiological impedances. As can be seen from Figure 41, the Current Control 197 communicates with Isolated Driver Circuitry 193. Advantageously, there is also safety circuitry, which includes Safety Fuse 199 and Isolated Safety Relay 198, controlled by Safety Relay Control 192. Shunt Control 196 then controls the Isolated Shunt Circuitry 170, which timely delivers the subpacing current output 194 to the subject.

Figure 42 is a schematic level of an exemplary isolated driver section. Blocked off on the schematic are Isolated Driver section 193, Safety Fuse 172, safety switch 174, and shunting circuitry 170. Additional techniques and means for improving sensing and analysis of cardiac signals will now be discussed, including both stimulated as well as non-stimulated signals. Such techniques and means include: wavelet decomposition, alternative or passive shunting, detection of ECG alternans, stimulation of alternans behavior, detection of differences between natural and stimulation induced alternans behavior, cardiomyopathy detection techniques, body surface shunting synchronous with the R-Wave on Signal Averaged Electrocardiogram, subthreshold stimulation without capture to reduce the stimulation threshold causing changes to the action potential of a subsequent suprathreshold stimulation with capture, Wedensky transthoracic stimulation, Wedensky phenomenon within the late potential region, wavelet analysis of subthreshold stimulated and control Signal Averaged Electrocardiograms in healthy subjects and ventricular tachycardia patients, QRS complex alternans detected by wavelet decomposition of Signal Averaged Electrocardiograms, and QRS background noise differentiation. Each such means will now be discussed, including reference to Figures 47-57. Wavelet Decomposition is a mathematical analysis allowing the study of a particular signal of interest in the presence of other signals. The analysis allows itself to be tuned towards higher sensitivity to one or more particular type(s) of waveforms while reducing sensitivity towards another. This type of analysis is particularly useful when used on ECG data. ECG data can contain specific environmentally present electrical noise, for example 50 Hz or 60 Hz. ECG data may also contain broadband constant or intermittent noise produced by local sources of electromagnetic interference. The dynamics of the ECG waveform itself (as it is produced by the heart) can be defined in both frequency and amplitude. Research has defined such an analyzing waveform for use with Wavelet Decomposition in studying ECG data. This application includes the use of such wavelet decomposition to analyze either the natural ECG or stimulated ECG data produced by an ECG device, including the devices disclosed herein. Also included is the use of wavelet decomposition to analyze combinations of natural ECG or stimulated ECG data produced by an ECG device, including the devices disclosed herein.

This application discloses, inter alia, the methods and apparatus of using the stimulation electrodes (or any large area surface electrodes) in an ECG device, including the devices disclosed herein, as a method of enhancing sensing of cardiac condition. First, these electrodes can act as a shielding mechanism to enhance the sensing of ECG signal. The presence of a large area electrode acts as an electrical shield allowing better sensing of cardiac signal. The use of such an electrode is identified and claimed here. Shunting is a technique of dissipating unwanted voltage. Use of the devices and methods disclosed herein involve the delivery of energy followed by the shunting of the stimulation leads as a means of reducing the artifact caused by charge remaining on the lead system. This shunting process also has application when no energy is delivered through the leads, and is interchangeably referred to herein as alternative or passive shunting.

By passively changing (shunting) the potential of a large area of the body, an impedance modulation in the body can be realized. The generation of the surface ECG from the heart involves the current flow from cell to cell as depolarization recruitment progresses. This current vector multiplied times the local resistivity gives the local electrical field. The components of that on the skin are what is called the ECG. By pulsing the shunt across the chest it is possible to modulate that resistance (i.e. "impedance modulation"). This is similar to changing the angle of view of the cardiac signal. This altered measurement can also be compared against the non-shifted measurement. Also disclosed here is the process of shunting these or any larger area surface electrodes together to effectively provide an isopotential at the skin surface. This action can be viewed as "passive stimulation." It can shift the body potentials and possibly alter conduction pathways to allow better sensing of the cardiac condition. This altered measurement can also be compared against the non-shifted measurement. The use of either "impedance modulation" or "passive stimulation" and its effect on the QRS signal is thus disclosed herein.

Alternan behavior consists of the changing of cardiac signal in a modal fashion. That is, one beat will have certain characteristics, the next will have different characteristics, and the following will have characteristics like the first. The process of averaging together alternate beats used in an ECG device, including the devices disclosed herein, allows the measurement of the natural ECG alternan behavior. The extent and change of this measurement can be a measure of cardiac condition. The use of this measurement as an indication of cardiac condition is disclosed and included in this application. By averaging together alternate beats, the systems and methods disclosed herein allows the measurement of alternan behavior. This method can be useful in the determination of cardiac condition. Thus, this application discloses use of the systems and methods to achieve stimulation-related changes in alternan behavior, or shunting/impedance shifting-related changes (passive stimulation in alternan behavior as a method for detecting cardiac condition). Furthermore, the differences between natural alternan behavior and stimulated alternan behavior can also be useful in determining cardiac condition. This application discloses and includes the use of the differences between these behaviors as an indicator of cardiac condition.

A further use of the devices and methods disclosed herein is to assess conduction pathway changes within the heart by examining the changes in ECG while stimulating and not stimulating the myocardium. Another use disclosed herein is to detect non-conduction related abnormalities of the heart including, but not limited to, cardiomyopathy. The changes invoked by the process of stimulating, shunting, or examining alternate beats could also be used to determine the extent of physical myocardial abnormality. Stimulation related changes, shunting and impedance shifting related changes (passive stimulation), or changes due to average of alternate beats as a method of detecting non-conduction related abnormalities are disclosed and included herein.

Applicants have further discovered improved means for signal analysis by analyzing the effect of body surface shunting synchronous with the R-wave on Signal

Averaged Electrocardiograms by comparing the differences between normal subjects and patients with ventricular tachycardia. This study investigated the effects of creating a body surface short circuit synchronous with the R-wave on the spectral profile of signal averaged electrocardiograms. In 35 patients with EP inducible ventricular tachycardia and in 30 healthy volunteers, 60 to 200 QRS complexes were digitally recorded using orthogonal leads. Synchronous with on-line R-wave detection, two surface patches corresponding to the orthogonal Z lead (a precordial patch and a left dorsal subscapular patch) were electrically connected with negligible impedance for 2 ms. The QRS complexes recorded in this way were averaged and compared with the same number of averaged QRS complexes recorded without surface shunting. Both high-gain signals were decomposed with 53 scales of Morlet wavelets of central frequencies 40 to 250 Hz and vector magnitudes of wavelet decompositions were constructed. The differences between these decompositions were characterized by their surface areas in windows of 0 to 10 ms, 10 to 20 ms, and 20 to 30 ms, etc., after surface shunting.

The area difference was substantially greater in healthy volunteers, as shown by the light bars in Figure 47, than in VT patients (dark bars) both immediately, i.e. 0-10 ms after surface shunting (p < 0.04) and 10 ms later (p < 0.03) but not later (p = 0.4 at 20 ms later, and p = 0.5 at 30 ms later). From this research data it may be concluded that short circuiting the body surface produces both recording artifact and physiological stimulus affecting the depolarization sequence. This stimulus is very short lived and is more marked in healthy hearts than in VT patients who are probably less susceptible to minor electrical provocations.

Applicants further compared high-gain electrocardiographic evidence of Wedensky

Phenomenon in healthy subjects and ventricular tachycardia patients. Of course it is known that Wedensky Phenomenon is the effect of a subthreshold stimulation without capture that reduces the stimulation threshold and changes the action potential of a subsequent suprathreshold stimulation with capture. To investigate whether this phenomenon can be documented after transthoracic subthreshold stimulation (2 ms. pulse of 5 to 40 MA between surface precordial and subscapular patches delivered synchronous with R-wave detection), 60 to 200 subthreshold stimulated QRS complexes were signal averaged and compared with the same number of average non-stimulated complexes recorded during the same experimental session. The electrocardiographic recordings were obtained with standard orthogonal leads. In order to detect even minor changes within the QRS complex, each lead of both stimulated and control averaged complexes were wavelet decomposed (53 scales of the Morlet wavelet with central frequencies of 40 to 250 Hz). The wavelet residuum corresponding to the Wedensky Phenomenon was obtained by subtracting the vector magnitude wavelet decomposition of the control QRS from the vector magnitude decomposition of the subthreshold stimulated QRS. The surface of the residuum was investigated in windows of 1 to 25 ms following the stimulation. The test was performed in 35 patients with EP inducible ventricular tachycardia and in 30 healthy controls. The wavelet residuum showed sharp increase in the spectral power of the stimulated complex that was significantly more marked in healthy volunteers (p < 0.01) than in VT patients. This is shown in Figure 48 in which there is 20 ms stimulation, and in which full circles are VT patients, and empty circles are control patients. This shows that Wedensky phenomenon induced by an external transthoracic subthreshold stimulation can be documented in man and differentiates VT patients from controls. In further investigation, patients with electrophysiologic documented ventricular tachycardia (n=35) and healthy controls (n=30) were subjected to a subthreshold external stimulation between precordial and left subscapular patches. Stimuli of 5, 10, 20, and 40 ma were delivered for 2 ms synchronous with R-wave detection. 60 to 200 subthreshold stimulated QRS complexes were averaged and compared with the same number of non-stimulated complexes. Vector magnitude wavelet decompositions (53 scales of central frequencies 40 to 250 Hz) were obtained for both stimulated and non-stimulated complexes and their difference characterized the Wedensky Phenomenon numerically. The surface area of the 3D envelope of the wavelet residuum was measured in a window ± 5 ms from the R peak (stimulation moment) and in surrounding 10 ms windows. The wavelet residuum showed a sharp increase of the surface of the 3D spectral envelope at and after the stimulation that was more marked in healthy volunteers than in VT patients, as shown in Figure 49 in which 40 ma experiments were conducted, and full circles are VT patients, and open circles are control patients. The maximum changes in wavelet residuum increased with stimulation subthreshold energy: 5 ma: control 1993 ± 181 technical units, VT patients 1488 ± 159; 10 ma: control 2151 ± 200, VT patients

1543 ± 154; 40 ma: control 2746 ± 332, VT patients 1842 ± 177, i.e. all were statistically significant. Thus, externally induced Wedensky phenomenon shows a dose response that is more marked in healthy volunteers than in VT patients.

Wedensky Phenomenon within the late potential region was analyzed utilizing dose-related separation of patients with ventricular tachycardia from healthy controls. Patients with EP documented ventricular tachycardia (n=35) and healthy controls (n=30) were subjected to a subthreshold external stimulation between precordial and left subscapular patches. Stimuli of 5, 10, 20, and 40 ma were delivered by 2 ms after a 20 ms delay following a real-time R-wave detection. 60 to 200 subthreshold stimulated QRS complexes were averaged and compared with the same number of non-stimulated complexes. Vector magnitude wavelet decompositions (53 scales of central frequencies 40 to 250 Hz were obtained for both stimulated and non-stimulated complexes and their difference characterized the Wedensky Phenomenon numerically. The surface area of the 3D envelope of the wavelet residuum was measured in a window 20±5 ms after the R peak (a window centered around the stimulation moment) and the subsequent 10 ms windows (30±5 ms after the R peak). The areas of the residuum spectral 3D envelope in these windows were statistically compared in the VT patients and healthy controls.

All differences were highly statistically significant, as shown in Figure 50 (up to p < 0.00005), with the manifestation being more pronounced in the control group. The separation of the groups was more significant in the window around the stimulation moment that in the subsequent window and the significance decreased with increasing subthreshold stimulation energy. Accordingly, a Wedensky phenomenon in the late QRS part is brief, and VT patients are less sensitive to the phenomenon, especially at very low subthreshold energies. In yet another assessment, patients with EP documented ventricular tachycardia

(n=35) and healthy controls (n=30) were subjected to a subthreshold external stimulation between precordial and left subscapular patches. Stimuli of 5, 10, 20 and 40 ma were delivered for 2 ms either simultaneously with the R-wave or 20 ms after the R-wave. 60 to 200 subthreshold stimulated QRS complexes were averaged and compared with the same number of non-stimulated complexes (reference). Vector magnitude wavelet decompositions (53 scales of Morlet wavelet with central frequencies 40 to 250 Hz) were obtained for both stimulated and non-stimulated complexes. Local maxima of the 3D spectral envelopes were counted in 50 ms windows following the subthreshold stimulation and compared in VT patients and healthy controls. In reference recordings, Figure 51 , there were no statistical differences between VT patients (shown as closed dots) and controls (open dots). In subthreshold stimulated recordings, the local maxima decreased (3D spectral envelopes became more smooth). This decrease was greater in healthy controls and with stimulation after the R wave, Figure 52, wherein all the differences except in experiment 10/00 were significant up to p < 0.001. Accordingly, subthreshold external stimulation makes the depolarization wave more uniform, mainly when delivered in the terminal QRS part in healthy volunteers.

Although the electrical alternans of the ST segment and T-wave has been extensively researched, the alternans of the QRS complex has generally not been investigated-mainly because of difficulties in detecting it. Applicants' innovations overcome such previous limitations, and allowed further assessment as follows. In 35 patients with EP inducible ventricular tachycardia and in 30 healthy volunteers, 120 to 400 QRS complexes were digitally recorded using orthogonal leads. From these sequences of beats, the complexes with even and odd order numbers were separately aligned and averaged. The resulting high gain signals were processed with wavelet decomposition (53 scales of Morlet wavelets with central frequencies of 40 to 250 Hz) and the differences between the resulting 3D spectral envelopes were computed. These created alternans-related 3D spectral envelopes and were characterized by surface areas in subsequent 10 ms windows.

The surfaces of the alternans-related 3D spectral envelopes were substantially larger, as shown in Figure 53, in VT patients (full circles) compared to healthy controls (open circles). The differences between the groups were particularly marked within the initial and terminal portions of the QRS complex (p < 0.00005 in the 10 ms window preceding the R wave by 40 ms). Thus, a wavelet decomposition of alternating signal averaged ECG is capable of detecting electrical alternans within the QRS complex, and the QRS complex alternans is significantly more expressed in VT patients compared to healthy controls. Also, the QRS complex alternans differs between VT patients and controls mainly at the beginning and at the end of the QRS complex.

Of the many improvements discussed above, it is worth noting that wavelet analysis is particularly significant. Indeed wavelet analysis is a highly reproducible method for SAECG processing which is as powerful as the time-domain analysis for the identification of ischemic VT patients. As compared to the time-domain analysis, wavelet analysis is not dependent on infarct site, and is able to distinguish post myocardial infarction patients without VT from healthy subjects. As compared to known applications of wavelet representations, Applicants utilized much finer distinctions of scales (7 vs. 54) with a different range of middle frequencies (70-200 Hz vs. 40-250 Hz). Applicants also determined that wavelet analysis of signal-averaged ECGs is superior to the standard time-domain analysis in predicting post myocardial infarction events. In particular, this analysis identifies not only those post MI patients who are at risk of non-fatal sustained ventricular tachycardia, but also those who are at risk of sudden cardiac death. Thus, this is the first discovery of using wavelet analysis for categorical risk analysis with prospectively collected signal-averaged ECG data in an almost consecutive population of MI survivors. As such, a significant advantage of this technology is that compared with standard time-domain analysis, the wavelet decomposition of signal-averaged ECGs provides a more powerful distinction between survivors of an acute MI who are and are not at high risk of further complications. Figure 54 shows sample data of the interdependence of time-domain and wavelet decomposition indices, in which is presented the correlation coefficient between the two techniques. The value of correlation coefficient is shown above the diagonal, and the corresponding p-values are displayed below. Figure 55 is data representing a comparison of signal-averaged ECG indices in patients with and without follow-up events. For each category of follow-up events and for each time-domain and wavelet decomposition parameters, the table lists the averaged value in patients with and without the event. The last column (p = ) shows the significance of statistical comparison of values in patients with and without events (nonparametric Mann- Whitney test). Figure 56 shows the association of positive SAECG findings with follow-up events. For each category of two year followup events and for each of four diagnostic criteria, the table shows the number of true positive (tp) and true negative (tn) patients as well as the statistical significance (p-) of the association of events with findings of a positive signal averaged ECG analysis (Fishers exact test). Herein, CM represents cardiac mortality, PAD represents potentially arrhythmic death, SCD represents sudden cardiac death, VT represents sustained ventricular tachycardia, PAE represents potentially arrhythmic events, and ARF represents sudden cardiac death and/or ventricular fibrillation. Figure 57 is a comparison of positive predictive accuracy of predicting follow-up events. In this Figure, for each category of follow-up events and for six selected levels of sensitivity (Sen), the table shows maximum positive predictive accuracy (PPA) achieved at that level of sensitivity with time-domain indices (TD) and wavelet decomposition indices (WD) of signal averaged ECGs. The table also shows the numbers of patients for which the diagnostic criteria of both techniques adjusted for the given level of sensitivity did not agree (Discordance) divided into the number of those for which the time-domain diagnosis was correct (TD+) and those for which the wavelet decomposition diagnosis (WD+). The last column shows the statistical significance (p=) of the comparison of values of TD+ and WD+ (sign test).

One additional signal improvement technique involves improved noise management in the QRS realm. When sensing signals from electrodes, a certain amount of environmental background noise is unavoidable. This noise may vary in frequency and direction, causing certain electrode placements to be more sensitive to receiving it than others. The following software-based approach addresses an implementation to reduce sensitivity to this background environmental noise during the processing of data recorded from electrodes.

To improve alignment of QRS complexes of multiple channel ECG data (XYZ, multi-lead intercardiac, 2 lead, etc.,) a mechanism which reduces sensitivity to background noise may be applied. The mechanism involves the determination of the signal level of the background noise and the signal level of the desirable signal (in the case of ECG data, the QRS). These parameters are determined for each data channel. The parameters are combined into ratios of Desirable/Background signals (hereby called D/B ratio). Channels with low D/B ratios are excluded from use during QRS alignment. Since it is possible for background noise to vary over time, an alternate implementation of this mechanism could be to assess the signal around each QRS complex for D/B ratio and exclude QRS's based on their individual ratios.

While the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the foregoing description. Accordingly, it is intended to embrace all such alternatives, modifications, and variations which fall within the spirit and broad scope of the invention.

Claims

WHAT IS CLAIMED IS:

1. A method for assessing heart characteristics comprising the steps of: providing means for injecting low level electromagnetic energy stimulations into a patient's body suitable to alter at least one cardiac signal to allow a comparison of acquired distinguishable signal differences with at least one other cardiac signal which has not been affected by said injected energy; connecting a lead system for both sensing the cardiac signals and delivering the injected energy to said means for injecting low level electromagnetic energy into the patient's body, said lead system, comprising a plurality of energy sensing and energy delivery leads; and utilizing sensing improvement means for improving the quality of the sensed electromagnetic energy during the stimulation and acquisition process.

2. The method of claim 1 wherein the sensing improvement means further comprises analysis of the cardiac signals with an algorithm comprising Wavelet Decomposition of the cardiac signal(s).

3. The method of claim 2 wherein the cardiac signals are natural.

4. The method of claim 2 wherein the cardiac signals are stimulated.

5. The method of claim 2 wherein the cardiac signals are a combination of natural and stimulated cardiac signals.

6. The method of claim 1 wherein the sensing improvement means comprises the step of providing the energy delivery leads with shunting means.

7. The method of claim 6 comprising the step of providing switch means configured to sense termination of an output current in the energy delivery leads and switch from a high impedance to a low impedance for a short period of time to allow dissipation of any voltage present.

8. The method of claim 6 wherein at least two of the leads are shunted together, whereby an isopotential at the surface of the skin may be provided.

9. The method of claim 6 comprising a large area electrode.

10. The method of claim 9 wherein the large area electrode is used for energy delivery.

1 1. The method of claim 9 comprising a means of controlling the potential of the large area electrode, whereby the large area electrode is used to passively change the potential of a large area of the body so that the impedance of the body may be modulated whereby impedance modulation is achieved.

12. The method of claim 1 1 wherein the step of impedance modulation is used to affect the QRS signal.

13. The method of claim 9 comprising the step of controlling the surface potential of the large area electrode so that the potential of the body may be shifted, whereby passive stimulation is achieved.

14. The method of claim 13 wherein the step of passive stimulation is used to affect the QRS signal.

15. The method of claim 1 in which the sensing improvement means comprises the steps of: stimulating at least one heartbeat, and comparing the stimulated heartbeat(s) to unstimulated heartbeats.

16. The method of claim 15 wherein the heart is stimulated on every other beat, whereby ECG alternans may be measured.

17. The method of claim 16 comprising the step of averaging heartbeat ECG data so that an improved comparison may be made.

18. The method of claim 16 wherein the step of stimulating of the heart comprises a shunting step.

19. The method of claim 16 wherein the step of stimulating of the heart comprises passive stimulation.

20. The method of claim 16 wherein the step of stimulating of the heart comprises impedance modulation.

21. The method of claim 16 wherein the differences in every other heart beat are compared so that indicator(s) of cardiac condition may be measured.

22. The method of claim 21 wherein every other heart beat is stimulated.

23. A device for detection of a patient's susceptibility to arrhythmias, the device comprising, means for injecting low level electromagnetic energy stimulations into a patient's body, the stimulations being suitable to alter at least one cardiac signal; means for comparing a cardiac signal affected by the injected energy stimulations to at least one other cardiac signal which has not been affected by said injected energy; a lead system for both sensing the cardiac signals and delivering the injected energy to said means for injecting low level electromagnetic energy into the patient's body, said lead system comprising at least one energy sensing and at least one energy delivery lead; and at least one sensing improvement means, for improving the quality of the sensed electromagnetic energy during the stimulation and acquisition process.

24. The device of claim 23 wherein the sensing improvement means comprises means for executing an algorithm comprising Wavelet Decomposition analysis of the cardiac signal(s).

25. The device of claim 24 wherein the cardiac signals are natural.

26. The device of claim 24 wherein the cardiac signals are stimulated.

27. The device of claim 24 wherein the cardiac signals are a combination of natural and stimulated cardiac signals.

28. A method for assessing cardiac condition comprising the steps of: providing means for injecting low level electromagnetic energy stimulations into a patient's body suitable to alter at least two cardiac signals to allow a comparison of acquired distinguishable signal differences between said at least two cardiac signals which are affected by said injected energy; connecting a lead system for both sensing the cardiac signals and delivering the injected energy to said means for injecting low level electromagnetic energy into the patient's body, said lead system comprising a plurality of energy sensing and energy delivery leads which are selectively functionally connectible at different positions, for delivery of optionally different energies for optionally different durations; and utilizing sensing improvement means for improving the quality of the sensed electromagnetic energy during the stimulation and acquisition process and comparing differences or similarities to determine cardiac condition.