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(12) United States Patent (1o) Patent No.: US 7,539,535 B1 Schlegel et al. (45) Date of Patent: May 26, 2009

(54) REAL-TIME, HIGH FREQUENCY QRS OTHER PUBLICATIONS ELECTROCARDIOGRAPH WITH REDUCED AMPLITUDE ZONE DETECTION Aversano et al., "High Frequency QRS in the Detection of Reperfusion Following Thrombolytic Therapy," Clini- (75) Inventors: Todd T. Schlegel, Nassau Bay, TX (US); cal Cardiology, vol. 17, pp. 175-182, Apr. 1994.* Jude L. DePalma, Pueblo, CO (US); Saeed Moradi, Houston, TX (US) * cited by examiner

(73) Assignee: The United States of America as Primary Examiner Kennedy 7 Schaetzle represented by the Administrator of (74) Attorney, Agent, or Firm Theodore U. Ro the National Aeronautics and Space Administration, Washington, DC (US) (57) ABSTRACT

(*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 Real time cardiac electrical data are received from a patient, U.S.C. 154(b) by 533 days. manipulated to determine various useful aspects of the ECG signal, and displayed in real time in a useful form on a com- (21) Appl. No.: 11/345,687 puter screen or monitor. The monitor displays the high fre- (22) Filed: Jan. 26, 2006 quency data from the QRS complex in units of microvolts, juxtaposed with a display of conventional ECG data in units Related U.S. Application Data of millivolts or microvolts. The high frequency data are ana- lyzed for their root mean square (RMS) voltage values and the (63) Continuation of application No. 09/906,013, filed on Jul. 12, 2001, now Pat. No. 7,113,820. discrete RMS values and related parameters are displayed in real time. The high frequency data from the QRS complex are (51) Int. Cl. analyzed with imbedded algorithms to determine the pres- A61 510472 (2006.01) ence or absence of reduced amplitude zones, referred to (52) U.S. Cl ...... 600/517; 600/509; 600/523 herein as "RAZs". RAZs are displayed as "go, no-go" signals (58) Field of Classification Search ...... None on the computer monitor. The RMS and related values of the See application file for complete search history. high frequency components are displayed as time varying signals, and the presence or absence of RAZs may be simi- (56) References Cited larly displayed over time. U.S. PATENT DOCUMENTS 7,113,820 132 * 9/2006 Schlegel et al ...... 600/523 9 Claims, 16 Drawing Sheets

USER INTERFACE: USER SELECTS THE TOTAL NUMBER OF PRECEDING 20 PC ECG CONSOLE 14 1 BEATS THAT WILL CONSTITUTE THE RUNNING TEMPLATE, THE % CROSS- CORRELATION REJECTION THRESHOLD, AND THE CHANNELS) THAT WILL --- 15 -- BE USED FOR THE CROSS-CORRELATION CALCULATIONS —36 — — —

R-WAVE DETECTION GENERATE INITIAL ORS RUN REAL-TIME CROSS- DEVICE DRIVER (WITH LOCAT/ONOF TEMPLATE USING FIRST CORRELATION FUNCTION 48 FIDUCIAL POINT) INCOMING BEAT ONEACH SUBSEQUENT INCOMING BEAT 40 56 L42 44 1 _50 1150-250 Hz BEATS 1NTEMPLATE ALL WELL-CORRELA- ALL POORLY CORRE DIGITAL BANDPASS FULLY ALIGNED BY TED BEATS ARE AC- LATED BEATS(THOSE DISPLAY FILTERING DETECTING/ADJUS- CEPTED TO CREATE BELOW CHOSE THRESH- TOTAL TING FORANYJITTER THE RUNNING OLD) ARE REJECTED NUMBER MPLATE OF BEATS 58 54 52 INSTANTANEOUS HF REJECTEL QRS RMSVetc. B POWER 8 CHANNEL TO FILTERED SIGILTERED QRS ON- AND AC- SPECTRUM GENERATED 12-LEAD (HFQRS)GENEANDk OFFSET AU- CEPTED FOR EACH LEAD USING CONVERSION TED FOR EACH ATICALLY DETER- THE UNFILTERED QRS LEAD ED 68 71 L---- 64 —I 62 I RUNNING PLOT OF HF QRS VE INSTANTANSOUS 70 RMSV etc.& RA Zs vs. TIME DETECTOR FOR 60 15 { 66 FOR EACH LEAD I LEAD — J USER INTERFACE: USER SELECTS THE TOTAL USER CAN MANUALLY(VISUALLY, NUMBER OF PRECEDING BEATS TO BE IN- SET THE UNFILTERED ORS ON- ICORPORA TED INTO THE SIGNAL AVERAGE I ISEr AND/OR OFFSET IF DESIRED U.S. Patent May 26, 2009 Sheet 1 of 16 US 7,539,535 B1

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oo a US 7,539,535 B1 1 2 REAL-TIME, HIGH FREQUENCY QRS interest in terms of off-line detection of and infarc- ELECTROCARDIOGRAPH WITH REDUCED tion are those signals in the range of 150 to 250 Hz. The raw, AMPLITUDE ZONE DETECTION analog ECG signal is typically sampled at ?500 samples per second (to digitize the signal) in order to adequately satisfy This application is a continuation of prior application Ser. 5 the Nyquist rate of sampling at least twice the highest fre- No. 09/906,013, filed Jul. 12, 2001, now U.S. Pat. No. 7,113, quency of interest and in order to retain the information in the 820. signal without loss. In the past, the sampled data have been The invention described herein was made by employees of stored, and then later processed to provide potentially useful the United States Government and may be manufactured and information to the researcher. used by or for the government for government purposes with- 10 out payment of any royalties thereon or therefore. On the other hand, Simpson, in U.S. Pat. No. 4,422,459, teaches a system which analyzes only the late portion of the FIELD OF THE INVENTION QRS interval and early portion of the ST segment, and in an off-line fashion (i.e. from previously stored data) to indicate The present invention relates generally to the field of elec- 15 cardiac abnormalities, in particular the propensity for cardiac trocardiography, and more particularly to a real-time process- . The late portion of a post myocardial infarct ing system and method to analyze and display electrocardio- patient's QRS waveform contains a high frequency (40-250 graphic signals. Hz) signal tail which is indicative of a tendency toward ven- tricular . The system in Simpson digitally pro- BACKGROUND OF THE INVENTION 20 cesses and filters a patient's QRS signals in a reverse time manner to isolate the high frequency tail and avoid the filter Diagnosis of abnormal cardiac conditions has relied in the ringing which would otherwise hide the signal. Thus, in order past on visible alterations in the P, QRS, and T-waves, i.e. to do so, Simpson presupposes that the data are stored so that portions of the electrocardiograph periodic signal. The elec- they can be processed in reverse time order. trocardiograph signal includes a low frequency portion and an 25 Albert et al. U.S. Pat. No. 5,117,833, partially focuses on impressed or imbedded high frequency portion, and it has analyzing signals within the mid-portion of the QRS interval been found that although the higher frequency portion of the for the indication of cardiac abnormality. The system of signal is not particularly visible, it contains information that Albert et al. uses a known technique ofbuilding up data points provides greater sensitivity in determining certain abnormali- to derive an average of heartbeat characteristics in order to ties, notably myocardial ischemia and infarction. 30 enhance signal to noise ratio. Data are collected and filtered The conventional electrocardiogram (ECG) can be a very and then stored for subsequent analysis. Thus, the system insensitive diagnostic tool. For example, a significant per- does not teach a cardiac monitor which provides the data centage of individuals presenting to a hospital emergency analysis immediately from the data derived from apatient, i.e. room with an actual (heart attack) will in "real-time". have a normal 12-lead conventional ECG. In addition, the 35 Albert et al., U.S. Pat. No. 5,046,504, similarly teaches the conventional ECG accurately reflects only the predominant acquisition of QRS data and subsequent analysis. Routine low-frequency electrical activity of the heart. It tells the cli- calculations are performed from the data previously calcu- nician little or nothing about the less predominant high fre- lated and stored. Further, this system teaches producing a set quency components of the heart's electrical signal embedded of digital spectrum values representative of an approximate within the various lower-frequency waves of the conventional 4o power density spectrum at each of a large number of generally ECG. equally spaced sampling time intervals of the ECG wave- From off-line studies, it is known that a diminution of the form. higher frequency components within the central portion of the QRS complex of the ECG can be a highly sensitive indi- Seegobin, in U.S. Pat. Nos. 5,655,540 and 5,954,664, pro- cator for the presence of myocardial ischemia or infarction, 45 vides a method for identifying . The more sensitive, for example, than changes in the ST segment method relies on a database of high and low frequency ECG of the conventional low-frequency electrocardiogram. How- data taken from known healthy and diseased subjects. Com- ever, until now, there has been no device capable of display- parison of the data has led to a "Score" component, indicating ing, in real time, changes in these high frequency QRS com- deviation of a patient's data from the norm. This reference is rather calculation intensive, and does not suggest monitoring ponents in the monitored patient. While academic software 50 programs have been designed that analyze the central high the condition of a patient, but rather is utilized as an off-line frequency QRS components, all such programs involve labo- diagnostic tool. rious off-line calculations and post-processing, and therefore Hutson, U.S. Pat. No. 5,348,020, teaches a technique of have little if any clinical utility, being strictly research tools. near real-time analysis and display. The technique includes Thus, there remains a need for a system and method that 55 inputting ECG data from multiple, sequential time intervals analyzes high frequency components over the entire QRS and formatting those data into a two-dimensional matrix. The interval inreal time for usefulness in the clinical environment. matrix is then decomposed to obtain corresponding singular Such a system should perform, in real time, all of the complex values and vectors for data compression. The compressed digital sampling, averaging, and filtering that is required to form of the matrix is analyzed and filtered to identify and generate high frequency QRS ECG signals. The system 60 enhance ECG signal components of interest. As with other should also thereafter update these high frequency QRS ECG systems, this reference focuses on late potentials, a fraction of signals, as well as other derived parameters, in real time on a the QRS interval, as the tool to identify cardiac disease. beat-to-beat basis, supplementing the diagnostic information Finally, High-Frequency Electrocardiogram Analysis of being obtained from the conventional (i.e. low frequency) the Entire QRS in the Diagnosis and Assessment of Coronary ECG complexes at the same time. 65 Artery Disease by Abboud (Progress in Cardiovascular Dis- The higher frequency signals in the central portion of the eases, Vol. XXXV, No. 5 (March/April), 1993: pp 311-328) QRS ECG complex that have generated the most research teaches the concept of "reduced amplitude zone" (RAZ) as a US 7,539,535 B1 3 4 diagnostic tool. However, this reference also uses post-pro- plays, juxtaposed in real time, to provide a side-by-side com- cessing, and provides no teaching of a real-time analysis parison of various aspects of the QRS complex in real time. system. These and other features of the invention will be apparent Thus, there remains a need for an electrocardiograph that to those of skill in the art from a review of the following analyzes, in real time, the high frequency components of the 5 detailed description along with the accompanying drawings. QRS complex in order to provide an effective monitor for patients with specific cardiac function abnormalities. The BRIEF DESCRIPTION OF THE DRAWINGS present invention is directed to such an electrocardiograph. FIG.1 is a schematic diagram of the overall system of this SUMMARY OF THE INVENTION 10 invention. FIG. 2 is a schematic diagram of a detail of FIG. 1. FIG. 3 is a schematic diagram of the logic carried out by the The present invention addresses these and other needs in invention. the art by providing a real time display of various aspects of FIG. 4 is a real-time screen display, showing characteristic the QRS complex. The invention also provides a system for 15 data obtained from a healthy subject, including a side-by-side such a display, and a method of displaying such aspects. display of a standard ECG and a filtered (high frequency) The present invention advances the state of the art by taking ECG. high frequency electrocardiographic data immediately as FIG. 5 is a real-time screen display, showing characteristic they are sensed from a patient, manipulating the data in con- data obtained from a patient having known cardiac disease, junction with the conventional low frequency signals, and 20 including a side-by-side display of a standard ECG and a displaying the high frequency data in real time in a useful filtered ECG. form on a computer screen or monitor. In one aspect, the FIGS. 6 and 7 are real-time screen displays, showing the invention displays the high frequency data from the QRS configuration of a QRS detector for a normal, healthy subject complex in microvolts adjacent to a display of the conven- and for a patient having known cardiac disease, respectively. tional ECG data in millivolts. In another aspect of the inven- 25 FIGS. 8 and 9 are real-time screen displays of cross corre- tion, the high frequency data are analyzed for their root mean lation between a running, continuously updated waveform, or square (RMS) voltage values (as well as for related values template, and a sensed waveform to determine departure from such as the high frequency energy (HFQE) and high fre- the template from one heartbeat to the next. quency integral of absolute value (HFAV), both described FIGS. 10 and 11 are real-time screen displays of short term hereinafter), with the discrete, lead-by-lead values being dis- 30 trends of various data for a healthy subject and for a patient played in real time as useful diagnostic indicators for having known cardiac disease, respectively. ischemia. Also, the high frequency data from the QRS com- FIGS. 12 and 13 are real-time screen displays of long term plex are analyzed with imbedded algorithms to determine the trends of various data for a healthy subject and for a patient presence or absence of reduced amplitude zones, referred to having known cardiac disease, respectively hereinafter as "RAZs". The given RAZ, of which there are at 35 FIGS. 14 and 15 are real-time screen displays of high least three possible variations (i.e., the `Abboud" RAZ, the frequency QRS skewness versus kurtosis for a healthy subject "NASA" RAZ, and the skewness-kurtosis or "S-K" RAZ, all and for a patient having known cardiac disease, respectively. described below), is displayed as a real-time "go, no-go" FIGS. 16 and 17 are real-time screen displays of the spec- signal on the screen. Finally, in still another aspect of the trum of power for normal and diseased patients, respectively. invention, not only the presence or absence any one of the 40 three variations of RAZs, but also the RMS and related values DETAILED DESCRIPTION OF A PREFERRED (HFQE and HFAV) are displayed against time as time varying EMBODIMENT signals. In still another aspect of the invention, the electrocardio- FIG. 1 shows a simplified, functional, block diagram of a graph of this invention detects and aligns R-waves and QRS 45 real-time high frequency QRS electrocardiograph 10 con- complexes and analyzes these ECG signals after digitization structed in accordance with the present invention. The inven- at high sampling rates of at least 500 samples per second, but tion monitors the cardiac function of a patient with a plurality preferably at sampling rates of 1000 samples per second or of patient electrodes 12. The electrodes provide measure- greater. The system also signal averages consecutive QRS ments of cardiac electrical function at various contact points electrocardiographic complexes in a user-adjustable fashion 50 on the skin of a patient in the conventional manner. For to increase the signal-to-noise ratio. The resulting averaged example, in the conventional 12-lead configuration, 10 elec- signal is filtered, using non-recursive digital bandpass filters trodes placed upon the skin of the patient in the conventional with varying high and low frequency cutoffs, and displayed in configuration result in eight channels of incoming data. These real time along with several other derived numerical measures eight channels are in turn translated into 12 leads of data on described herein including the power spectrum of the filtered 55 the patient monitor inasmuch as data for one of the bipolar data. The resulting displays provide a clinician with real-time limb leads and for all of the augmented unipolar limb leads information with respect to changes in the high frequency can be derived if data for any two of the bipolar limb leads are ECG complex that may be indicative of myocardial ischemia, already known. The analog measurements are coupled to a myocardial infarction, or of changes in myocardial conduc- console 14 by way of a communications channel such as for tion that are unrelated to myocardial ischemia or infarction. 60 example a cable 13. The console components are shown in The invention includes a number of features that are neither greater detail in FIG. 2. shown nor suggested in the art, including a real-time display The console 14 conditions and digitizes the analog signal of cardiac electrical data that have been manipulated in such and provides the digitized signal to a computer 16 by way of a way as to provide a clear indication of ischemia and infarc- a communications channel 15, which may preferably be a tion. The invention further includes a number of user select- 65 conventional cable or a wireless communication channel by able parameters to enhance the information provided to the radio frequency wave. The structure and function of the com- clinician. Finally, the invention provides a number of dis- puter is shown and described below in respect of FIG. 3. The US 7,539,535 B1

5 6 computer 16 is programmed to display the ECG signal in real which are below the threshold set by the user (or set by the time, although the ECG signal may also be stored on a digital system default) are rejected, with block 52 accepting only recording medium 18 over a communications channel 17 for well-correlated beats to create the running templates. This later display over a communications channel 17'. feature helps to eliminate noisy, unreliable waveforms when The computer 16 is coupled to a user interface 20 which 5 creating the running templates. From this block, the user preferably includes communications devices 22 such as a interface displays a continuously updated running total of the mouse, keyboard, and/or touch screen. The user interface number of beats accepted and rejected in block 51, a feature further includes a monitor 24 for user controllable graphic of the invention. display of the ECG and various aspects of the signal, a feature Block 54 then aligns the beats by detecting and adjusting of the present invention. The computer 16 is coupled to the io for any signal jitter, which may be created by any number of interface 20 by way of bidirectional communications chan- well-known factors, including minor inconsistencies in the nels 19 and 19', for example. The aspects of the graphical detection of the fiducial point, movement by the patient or display are shown in greater detail and described below in even respiration by the patient. The aligned, jitter-corrected respect of FIGS. 4 through 17. waveform is then fed to block 56, a band-pass filter, prefer- FIG. 2 depicts the structure of the console 14 in greater 15 ably 150-250 Hz, to select only the frequencies of interest in detail. As previously described, the patient is wired with a set the waveform. Finally, the band-pass signals are fed to block of electrodes 12, such as for example a conventional set of ten 58, where, in the present embodiment, the eight channel to electrodes for a 12-lead electrocardiograph to monitor car- 12-lead conversion is performed. diac function from different aspects of the patient's body. The From this point in the diagram of FIG. 3, blocks 62,64,68, electrodes 12 provide a set of analog electrical signals to the 20 70, and 72 describe data which are displayed on the user console 14, where they are received by a pre-amplifier 30 to interface 20, as shown in FIGS. 4 through 17. Block 62 shows boost the amplitude of the weak ECG signals. The amplified the instantaneous, real-time high frequency filtered QRS sig- signals are then fed to an anti-aliasing filter 32. The filtered nal for each lead, updating with each new beat as that beat is signals are then fed to an analog to digital converter 34, where incorporated into the average beat. Beats that are poorly the signals are digitized at least the Nyquist rate, preferably 25 cross-correlated are rejected and thus the template averages

1,000 Hz or greater, to retain all of the information contained and the display will not be altered by such beats. The display in the analog signals. The sampled/digitized signals are then is shown by element number 114 in FIG. 4. sent to the computer 16 by an appropriate medium 15. Block 64 determines the unfiltered QRS interval onset and The operation of the computer 16 is depicted in FIG. 3. The offset automatically and in real time. This block receives an console 14 feeds the digitized ECG signals to the computer so input from block 54 which detected and adjusted for any jitter via a communications channel 15, as previously described. in the well cross-correlated beats. The cross-correlation and The computer 16 also interfaces with the user interface 20. jitter-correction from block 54 are therefore also displayed on

The computer 16 receives the ECG signals into a device driver the user interface, as shown in FIGS. 8 and 9. Block 68

40, which is simply the interface device and program for the describes the display of the instantaneous high frequency console and computer. The device driver 40 provides the ECG 35 QRS RMS, HFQE and HFAV voltages and power spectrum signals in parallel to an R-wave detection block 42 to syn- generated for each lead using the unfiltered QRS interval chronize the system for the start of each heartbeat by locating onset and offset, and shown in FIG. 4 as element numbers 116 the fiducial point. The following requirements must be met and 128. for temporal averaging to work effectively. First, the signal of Block 70 describes the running plots of the RAZs ("go/no- interest must be repetitive and relatively invariable. Time 40 go") as well as the voltages for the RMS, HFQE and HFAV of varying signals, such as ectopic or premature complexes, are the high frequency QRS ECG signal versus time for each lead eliminated before averaging by comparing incoming signals as depicted in FIGS. 10 through 13. FIGS. 10 (healthy sub- against a previously established template through the use of a ject) and 11 (subject with known coronary artery disease) real-time cross-correlating technique. Second, the signal of depict short-term data trends whereas FIGS. 12 (healthy sub- interest must be timelocked to a fiducial point, such as near 45 ject) and 13 (subject with known coronary artery disease) the peak of the QRS complex, that is easily detectable and depict longer-term data trends. The horizontal (time) axis serves as a timing reference forthe averaging algorithm. If the scale is user-adjustable on both the long and short-term trend signal of interest does not have a fixed, temporal relationship plots, and can be shown either in beats (as depicted here) or in with the timing reference point, the resultant averaged signal seconds. Clinicians can utilize these trends to assess how a will be filtered and distorted due to reference jitter, with 50 monitored patient's cardiac function has changed over time, subsequent loss of the high frequency components. Third, the up to and including the present time. Specifically, clinicians signal of interest and the noise must be independent and can identify whether and when RAZs have developed or remain independent during averaging. disappeared during the period of monitoring, as well the

Once the fiducial point has been located for each incoming degree to which the RMS and related voltages of the high beat, the digitized signals are fed to block 44 where initial 55 frequency QRS complex have changed over the same period templates of the QRS complexes are generated. The present of monitoring. Realization of such changes is particularly invention includes running signal averages of the QRS com- valuable to clinicians during situations when the presence or plexes that constitute templates, with the number of indi- absence of incipient myocardial ischemia or infarction needs vidual beats in the running templates being selectable by the to be immediately identified, when the success or failure of user on the user interface 20. The user can also determine the 60 invasive or noninvasive treatments administered for ischemia percent of cross -correlation between each new incoming beat and infarction needs to be immediately recognized, and/or and the templates which will be detected as a departure from when cardiovascular responses during pharmacological or the norm, and which channel(s) that will be used for the exercise stress tests or during apatient's ambulatory activities cross-correlation functions. needs to be assessed. With the user-selected inputs as just described, the system 65 Finally, block 72 describes another feature of the invention, in block 48 runs a real-time cross-correlation function on online instantaneous RAZ detection for each lead. The pres- each subsequent incoming beat. In block 50, those beats ence of a "RAZ", or "reduced amplitude zone" within the US 7,539,535 B1 7 8 envelope of the averaged high-frequency QRS signal, may be to orbelow the conventional ECG display 112 is a display 114 an indication of abnormal cardiac function. A RAZ, as origi- of a running, instantaneous filtered (i.e. high frequency) QRS nally defined by Abboud (but only in the context of off-line ECG signal, one for each of the twelve leads, corresponding analyses), classically occurs when at least two local maxima to the individual leads of the display 112. The display signal of the upper envelope or two local minima of the lower 5 114 includes the signals from leads I, II, III, aVR, aVL, aVF, envelope are present within the high frequency QRS signal. A and V1-V6 to correspond to like signals in the display 112. local maximum or minimum is in turn defined as an envelope Above each high frequency QRS signal is the instantaneous sample point (peak or trough) within the QRS interval RMS value 116 in that particular lead, and an instantaneous wherein the absolute value of its voltage exceeds that of the RAZ indicator 117, defaulted to the RAZ type of the user's three envelope sample peaks immediately preceding and fol- l0 choice (in this case the RAZ, ). lowing it. The RAZ is thus the region lying between the two neighboring maxima or minima. The present invention per- At the bottom of the screen display of FIGS. 4 and 5 is a forms a real-time calculation, looking for local maxima and tool bar 120. The tool bar 120 provides user control and minima of the QRS envelope not only according to previously display of various data useful to the clinician. The tool bar published off-line criteria of Abboud (i.e., "RAZ,", or the 15 includes a user selectable indicator 122 in which the user can Abboud RAZ) but also separately and especially according to select which of a plurality of QRS complexes to capture. new criteria that improve the specificity and accuracy of RAZ Displays 124,126, and 128 show the timing of the QRS onset, detection, particularly for the online setting. QRS offset, and the duration of the QRS complex, respec- One especially important modification contributing to such tively. A display 130 shows the total number of heartbeats improvement is the requirement that the second, smaller local 20 which have been detected during any particular run, while a maximum within the high frequency QRS signal that defines display 132 shows the number of beats rejected and a display the presence of the RAZ be at least two times, and optionally 134 shows the number of beats whose processing is pending, up to three to four times, larger in amplitude than the RMS if any. Toggle buttons 136 and 138 permit the user to turn on "noise" of the high frequency signal that is present outside of and turn off the cross correlation function and the beat rejec- the QRS interval (i.e., in any given chosen segment within the 25 tion function, respectively. Display buttons 140, 142, 144, PR, ST or TP intervals). Another modification criterion and 146 permit the user to select other displays for the screen, implemented optionally by the user into the online RAZ as shown. A toggle button 148 permits the user to turn on and detector is that the absolute value of the amplitude of the turn off an autoscale function, and a print button 148 permits smaller of the two local maxima (or minima) constituting the the user to print a particular screen capture at his discretion. RAZ must be at least a certain percentage of that of the larger 30 Of particular note, in comparing FIGS. 4 and 5, is the small of the two local maxima (or minima). These modifications as number of reduced amplitude zones and lit RAZ indicators optionally implemented by the user within the present inven- 117 for the healthy patient shown in FIG. 4, versus the much tion, together with the requirement that at least two local larger number of reduced amplitude zones and lit RAZ indi- maxima of the upper envelope "and" (rather than "or") two cators for the subject with known coronary artery disease, local minima of the lower envelope be present to constitute a 35 shown in FIG. 5. RAZ, are collectively referred to as the criteria that define the "NASA RAZ", or "RAZA '. FIGS. 6 and 7 show configuration screen 160 for the online Yet another novel set of user-selectable criteria used in the QRS interval detector of the invention, selectable by button present invention to assess the presence or absence of a "sta- 146 of FIGS. 4 and 5. The configuration screen of FIGS. 6 and 7 permits the user to select a period within the P-R interval of tistical" type of RAZ concerns the use of real-time calculation 40 of the both the skewness and the kurtosis of the incoming high the ECG, with specific pre-Q offset and interval width selec- frequency QRS signal. When present, the skewness-kurtosis tors 162 and 164, respectively, that will aid in the determina- type of RAZ is referred to as the RAZ,-K. The presence of a tion of the onset of the QRS complex. The values for these RAZ,, RAZr„ and/or RAZSK by "go/no-go" indicators on parameters shown in FIGS. 6 and 7 have been selected based the display, as shown by element 117 in FIG. 4, may also be 45 on initial experience to provide satisfactory performance of displayed as a running parameter with time, in a manner the invention for the broadest array of subjects, since cardiac similar to FIGS. 10-13. function typically varies from patient to patient. Similarly, Referring now more particularly to FIGS. 4 and 5, a feature selectors 166 and 168 permit the user to select the offset and of the present invention is the simultaneous display in real- width, respectively, of a portion of the ST segment that will aidinthe determination ofthe offset ofthe QRS complex. The time of various aspects of cardiac function with respect to 50 both the conventional and high frequency QRS ECG. Further, configuration screen 160 also displays various parameters the present invention provides simultaneous, side-by-side or measured from the current heartbeat, as shown. An indicator vertical displays of that data to provide the clinician with a 170 shows the user which of the leads is selected, in the case tool to compare these aspects of the ECG with one another for of FIGS. 6 and 7 that lead is lead II. A RAZ indicator 117 is also provided for the convenience of the user. a more complete picture of cardiac function than has been 55 previously available. The present invention also displays the FIGS. 6 and 7 also include superimposed displays of a low conventional and high frequency 12-lead configurations on frequency signal averaged ECG 172 and an averaged high one user interface display, while displaying the presence or frequency filtered signal 174. The ordinate on the left of absence of RAZs on the same display to alert the clinician to FIGS. 6 and 7 shows the averaged low frequency signal 172 in potentially abnormal cardiac function. 60 millivolts, and the ordinate on the right shows the averaged The display of FIGS. 4 and 5 includes a conventional, low high frequency signal 174 in microvolts. frequency ECG signal, designated by the element number FIG. 6 shows a single local maximum 176 and a single 112. The display signal 112 includes the signals from leads L, local minimum 178. However, FIG. 7, depicting the wave- II, III, aVR, aVL, aVF, and V1-V6 in the conventional man- forms for a patient with known coronary artery disease, shows ner. Further, the display signal 112 slides from left to right, 65 two local maxima 180 and 182, and two local minima 184 and updated with each beat, also in the conventional manner, as a 186. Since the maxima and/or minima occur within the QRS reference for the clinician. Positioned immediately adjacent complex, and are separated by at least three envelope sample US 7,539,535 B1 9 10 points with lesser absolute amplitudes between them, they duration as defined by ufqon and ufqoff. In this context, the define a reduced amplitude zone as also shown on the lit RAZ term "onset' means the start of the QRS interval, and the term indicator 117. "offset" means the end of the QRS interval. This is the pri- FIGS. 8 and 9 depict cross correlation screens 190 of the mary numerical measure used in preferred embodiment of the invention. The screen 190 is selected by a user with button 5 present invention. 144 (FIG. 4). The screen includes a display 192 of a template, averaged over a user selectable number of beats. A display Other numerical measures of the high frequency QRS sig- 194 shows the low frequency ECG of the current beat, and a nal have also been proposed (and used strictly in an off-line display 196 shows the cross correlation between the wave- fashion) by Xue et al. (see Xue, Q., B. R. Reddy, and T. forms of display 192 and display 194. A user may select the io Aversano. Analysis of high-frequency signal-averaged ECG threshold for the cross correlation, below which the beat is measurements. J Electrocardiol 28: 23945, 1995). These rejected, by a selector 197 and, if a beat is rejected, an indi- numerical measures include the high frequency integral of cator light 198 illuminates. absolute values (HFAV) and the high frequency QRS energy Note that in FIG. 9 the current heartbeat shown on the 15 (HFQE). Xue et al. have defined HFAV and HFQE as follows: display 194 is noisy and has a different shape than the tem- plate. The current beat is also shifted in time from the tem- plate of display 192. Consequently, the cross correlation ugojj+10m between them is poor, as reflected in the display 196, which HFAV = Y^ IX; — AVNLI only has a peak of 0.951 (i.e. below the user selectable thresh- i—q —10ms old set at 0.970 in this case) and the beat is rejected, as shown 20 by the indicator light 198. Thus, the current beat is not incor- porated into the running template of the averaged ECG. and, FIGS. 10 through 13 depict trend lines for the RMS, HFQE, and HFAV, as well as show the current value for these parameters. These displays further include lines depicting the 25 goff+10m HFQE _ Z (X; — AVNL)' presence versus the absence of three types of RAZ as i—q —10ms described herein. These displays illustrate another feature of the present invention, that of showing a trend of parameters overtime. Specifically, the trend lines shown on a screen 200, which are continuously updated in real time, illustrate the 30 wherein AVNL equals the average noise level of the filtered presence (versus the absence) of all three types of RAZs over signal in the ST segment in a 40 ms window located 60 ms a user-selectable period of time (always up to and including from the QRS offset. It should be noted that in their own the present time) as well as the voltage trends for RMS, HFQE definitions for HFAV and HFQE (as shown above), Xue et al. and HFAV over this same user-selectable period of time for all "pad" both the QRS onset and offset by extra 10 ms each in an the leads attached to the patient. FIGS. 10 and 11 provide 35 effort to reduce noise and noise variability, presumably to examples of trend lines on a short-term time scale for a compensate for potential inaccuracies and inconsistencies healthy subject and for a patient with known coronary artery related to the determination of the QRS interval. disease, respectively, whereas FIGS. 12 and 13 provide cor- In the presently preferred embodiment of the present responding examples of trend lines on a long-term time scale 40 invention, the definitions for HFAV and HFQE are modified for these same individuals. The short and long-term trend line in two ways. First, because the present invention provides a plots can be accessed simultaneously by the user, and, to means of viewing the high and low frequency ECG signal in reiterate, the time intervals (horizontal axes depicted here in real time, thereby providing reliability for the determination units of beats) on both plots are completely selectable by the of the QRS interval, the necessity (or lack thereof) of using user. The particular parameters depicted on these plots are intended to be illustrative only, and other parameters may be 45 the 10 millisecond padding periods is left to the discretion of similarly illustrated. The ordinate for each plot is in micro- the user. Second, the present invention preferably uses the PR volts with respect to the RMS, BFQE and HFAV (the RAZs interval or TP segment rather than the ST segment to deter- are unitless, "go versus no-go" entities), whereas the abscissa mine the AVNL of the baseline, since a segment of the cardiac can be in either beats or seconds, for characterization of the cycle wherein neither depolarization nor repolarization is trend. 50 present is preferred. In the device of the present invention Numerical measures of the high frequency QRS ECG may disclosed herein, AVNL is determined as the RMS noise of be calculated in several ways. These measures are important the filtered signal that is within a 25 ms interval in the PR because they often decrease when ischemia is present. Per- segment. haps the most popularmeasure is the root mean square (RMS) 55 In the preferred embodiment, HFAV is measured as: voltage of the QRS signal, which is equivalent to the "area under the curve" of the power spectrum, defined as ugojj HFAV = Y. IX; —AVNLI i=uq- f9 jf °Y_ Xz 60 jgon RMS = UFQRSD whereinAVNL (average noise level) equals the "noise" of the high frequency (i.e., filtered) signal within that portion of the where X, is the filtered voltage at a given sampling point, 65 PR interval just noted. ufqon and ufqoff are the onset and offset, respectively, of the Further, high frequency QRS energy (HFQE) is calculated QRS interval, and UFQRSD is the unfiltered QRS interval as: US 7,539,535 B1 11 12 2. The process of claim 1, wherein the step of analyzing the data within the QRS interval further comprises the steps of 9 8 using the data processor to generate an initial template of HFQE = Y. ( X; - AVNL)' the signal using the first QRS interval from the first wave i=uq- 5 of the signal; using the data processor to cross-correlate each subsequent independently isolated QRS interval against predeter- wherein AVNL is determined in the same way as for HFAV. mined criteria wherein accepted QRS intervals are A useful characterization of a set of data includes skewness incorporated into the initial template to create a running and kurtosis. Skewness is a measure of symmetry, or more 10 template in real-time; accurately, the lack of symmetry. A distribution, or data set, is using the data processor to align each independently iso- symmetric if it looks the same to the left and right of the center lated QRS interval with the running template in real- point. Kurtosis is a measure of whether the data are peaked or time; and flat relative to a normal distribution. That is, data sets with a using the data processor to calculate predetermined, select- high kurtosis tend to have a distinct peak near the mean, 15 able characteristics of each QRS interval in a beat-by- decline ratherrapidly, andhave heavy tails. Data sets with low beat, real-time manner. kurtosis tend to have a flat top near the mean rather than a 3. The process of claim 2, wherein the step of using the data sharp peak. A uniform distribution would be the extreme case. processor to calculate is comprised of calculating a reduced By displaying skewness values alone, kurtosis values alone, amplitude zone, or skewness versus kurtosis graphically with one value on the 20 wherein the reduced amplitude zone occurs when at least ordinate and the other on the abscissa, the clinician may two local maxima or at least two local minima are obtain information from the high frequency QRS signals present in the filtered data; and potentially indicative of cardiac disease. Referring to FIGS. wherein each local maximum or each local minimum is a 14 and 15, a display 250 is provided to show real-time, con- peak or a trough, respectively and wherein the absolute tinuously updated plots of skewness versus kurtosis against a 25 value of each peak or trough's voltage exceeds that of a background line of a normal population distribution function. predetermined number of sample points within the fil- If a patient's S-K data in any given lead fall on or above that tered data immediately preceding and following each lead's distribution function, the data for that lead are consid- peak or trough. ered "normal", as shown in most of the leads of FIG. 14, 4. The process of claim 3, wherein the absolute value of the whereas data from any given lead falling below that lead's so amplitude of the smallest of the at least two local maxima or distribution function, as shown in most of the leads of FIG. the smallest of the at least two minima is at least a predeter- 15, provides a visual indication of potential cardiac disease, mined percentage relative to the largest of the at least two i.e., a positive "RAZs-x7'• maxima or the largest of the at least two minima, respectively. Referring now to FIGS. 16 and 17, a display 270 is pro- 5. The method of claim 3, wherein the absolute value of the vided to show the power spectrum of the high frequency QRS 35 amplitude of the smallest of the at least two local maxima or signal for each lead. A change in the shape of the spectral plot the smallest of the at least two local minima is at least a such that two distinct peaks occur rather than one may be predetermined multiple of the high frequency noise level of a further indication of cardiac malfunction. predetermined iso-electric portion. The principles, preferred embodiment, and mode of opera- 6. The method of claim 2, wherein the step of using the data tion of the present invention have been described in the fore- 40 processor to calculate is comprised of calculating a skewness, going specification. This invention is not to be construed as kurtosis, or both of the filtered data. limited to the particular forms disclosed, since these are 7. The process of claim 1, wherein the step of using the data regarded as illustrative rather than restrictive. Moreover, processor to independently analyze is further comprised of variations and changes may be made by those skilled in the art using the data processor to compute the presence or absence without departing from the spirit of the invention. 45 of reduced amplitude zones from the high frequency filtered data associated with the QRS interval. We claim: 8. A process of operating a computer, comprised of a gen- 1. A process of operating a computer, comprised of a gen- eral purpose data processor of known type, to enable the data eral purpose data processor of known type and a display processor to execute a plurality of steps in an object program, device, to enable the data processor to execute a plurality of 50 such that the same results will be produced when using the steps in an object program, such that the same results will be same given data, comprising the steps of produced when using the same given data, comprising the a. inputting a patient's electrocardiograph signal to the steps of computer via a communications channel, the signal a. inputting a patient's electrocardiograph signal to the comprising a succession of waves; computer via a communications channel, the signal 55 b. using the data processor to independently isolate the comprising a succession of waves; QRS interval from each of the waves of the signal; b. using the data processor to independently isolate the c. using the data processor to independently analyze data QRS interval from each of the waves of the signal; within each of the QRS intervals relating to cardiac c. using the data processor to independently analyze data function of a patient in real-time, the step of analyzing within each of the isolated 60 including band-pass filtering the data between about 150 QRS intervals relating to cardiac function of a patient in Hz and about 250 Hz; real-time, the step of analyzing including band-pass fil- d. connecting a storage device to the data processor; and tering the data between about 150 Hz and about 250 Hz; e. using the storage device to store the analyzed data, the and signal, the waves of the signal, the QRS intervals, or any d.using the display device to display the analyzed data, the 65 combination. signal, the waves of the signal, the QRS intervals, or any 9. An electronic storage database of the analyzed data, the combination beat-by-beat in real-time. signal, the waves of the signal, the QRS intervals, or any US 7,539,535 B1 13 14 combination resulting from the process described in claim 8 wherein the database is stored in the storage device.