WO2010077305A1

WO2010077305A1 - Measurement of extent of cardiac muscle injury

Info

Publication number: WO2010077305A1
Application number: PCT/US2009/006549
Authority: WO
Inventors: Paul David Phillips
Original assignee: Heartscape Technologies, Inc.
Priority date: 2008-12-15
Filing date: 2009-12-15
Publication date: 2010-07-08
Also published as: EP2373215A1; CA2746992A1; JP2012511998A

Abstract

An ST deviation volume (STDV) parameter is determined based on a magnitude of ST deviation observed by an electrode in a ECG device and an area associated with the electrode. For instance, the STDV may be calculated by multiplying the magnitude of ST deviation with an area factor obtained using regional electrode density. An aggregate STDV is determined using STDV values obtained from a plurality of electrodes. A method by which a physician may interpret an aggregate STDV value is also provided. In some embodiments, diagnostic threshold and classification bands may be obtained from a database of aggregate STDV values from a plurality of patients with confirmed diagnoses. An aggregate STDV value of the new patient may be compared against the diagnostic threshold and classification bands to determine whether the new patient is suffering from myocardial infarction (Ml), and if so, to classify the new patient's condition.

Description

MEASUREMENT OF EXTENT OF CARDIAC MUSCLE INJURY

BACKGROUND OF THE INVENTION

1. Field of Disclosure The present disclosure relates generally to methods for quantifying the extent of cardiac muscle injury in various regions of a patient's heart based on data collected from an array of electrodes in an electrocardiograph (ECG). The disclosure also relates to methods for classifying the overall extent of cardiac muscle injury in a patient and for diagnosing myocardial infarction (Ml) based on the classification of the overall extent of cardiac muscle injury.

2. Discussion of the Related Art

An ECG is a device comprising a plurality of electrodes applied to the skin of a patient in the thoracic region. These electrodes measure electrical activities in different areas of the cardiac muscle. An ECG is a useful tool for diagnosing various cardiac disorders, such as Ml and ischemia. In the case of acute Ml (also known as heart attack), an ECG may be useful for identifying the damage to the cardiac muscle.

The electrical signal recorded by an electrode may be traced on a standard grid, an example of which is shown in FIG. 1. On such a grid, time is represented horizontally, progressing from left to right, and voltage is represented vertically. In the particular example shown in FIG. 1 , each square has a width of 0.04 sec and a height of 0.1 mV.

FIG. 1 illustrates an exemplary ECG waveform of a normal heartbeat (or cardiac cycle). As shown, each beat comprises a P wave 110, a QRS complex 120 and a T wave 130. A portion 140 of the trace between the P wave and the QRS complex is known as the PQ segment, and a portion 150 of the trace between the QRS complex and the T wave is known as the ST segment. A small U wave 160 is also visible in this example, although in general U waves are not always visible in normal heartbeats. The baseline voltage of the ECG waveform is known as the isoelectric line and is shown as line 170 in FIG. 1. Typically, the isoelectric line is determined according to the portion of the trace following the T wave and preceding the next P wave.

1840114 l.DOC Cardiac muscle injury may be indicated by an elevation or depression of the ST segment of an ECG waveform. The ST segment is said to be elevated if it is at higher potential compared to the PQ segment of the waveform. An exemplary waveform exhibiting ST elevation is shown in FIG. 2A, where the magnitude of elevation is represented by the distance d1 between the potential of the ST segment 210 and the potential of the PQ segment 220. Similarly, the ST segment is said to be depressed if it is at lower potential compared to the PQ segment. An exemplary waveform exhibiting ST depression is shown in FIG. 2B, where the magnitude of depression is represented by the distance d2 between the potential of the ST segment 230 and the potential of the PQ segment 240.

ST deviation is often associated with cardiac injury. For example, elevation is often associated with ST elevation myocardial infarction (STEMI), and depression is often associated with ischemia, which may be a pre-cursor to evolving Ml. Traditionally, a 12-lead ECG is used to detect such abnormalities. However, due to the relatively small number of electrodes (typically 10), a 12-lead ECG can only indicate the presence of STEMI and the general area that is affected (e.g., septal, anterior, lateral). Often, STEMI is detected on as few as 2 electrodes, making it difficult to obtain sufficient information regarding the location and extent of the injury. In addition, a 12-lead ECG places most of the electrodes on the front of the chest, resulting in limited reliability in identifying STEMI occurring in other areas. For example, the 12-lead ECG has been known to miss STEMI occurring at the back surface of the heart.

Due to these limitations of a 12-lead ECG, other imaging modalities, such as angiogram, MRI, and echocardiogram, have been used to estimate the area of affected cardiac tissue. These imaging methods require specialized equipment and interpretation, and are therefore more costly and inconvenient for the patient.

More recently, ECG devices with more electrodes, for example, 40 to 100 electrodes, have been developed to provide more comprehensive information on the electrical activity of the heart. This technique, which is sometimes referred to as body surface mapping (BSM), uses a large array of electrodes to cover a patient's torso. An example of a BSM arrangement is illustrated in FIGs. 3A and 3B, with FIG. 3A showing electrodes 310 and 320 applied to the front of the thoracic region and FIG. 3B showing

1840114 1.DOC electrodes 330 applied to the back of the thoracic region. Further examples of BSM arrangements and devices are described in detail in U.S. Patents No. 5,419,337 and No. 6,055,448.

Brief Summary of the Invention

In accordance with some embodiments of the invention, a method for quantifying an extent of cardiac muscle injury is provided. The method comprises determining a magnitude of ST deviation based on electrocardiographic data obtained from at least one electrode in an electrocardiograph, the at least one electrode being associated with at least one region of a heart; determining an area factor for the at least one electrode, the area factor being associated with the at least one region; and computing an ST deviation volume for the at least one electrode, based, at least in part, on the magnitude of ST deviation and the area factor.

In accordance with some further embodiments of the invention, a computer- readable medium having computer-executable instructions for carrying out the above method is provided.

In accordance with some further embodiments of the invention, a method for diagnosing a patient based on aggregate ST deviation volume is provided. The method comprises: obtaining an aggregate ST deviation volume of the patient based on magnitude and area information collected from an array of electrodes applied to the patient; obtaining one or more diagnostic thresholds using aggregate ST deviation volume data from a plurality of patients with confirmed diagnoses; and comparing the aggregate ST deviation volume of the patient against the diagnostic thresholds.

In accordance with some further embodiments of the invention, a system for quantifying an extent of cardiac muscle injury based on electrographic data obtained from a patient is provided. The system comprises one or more processors programmed to: determine a magnitude of ST deviation based on electrocardiographic data obtained from at least one electrode applied to the patient, the at least one electrode being associated with at least one region of a heart; determine an area factor for the at least one electrode, the area factor being associated with the at least one region; and

1840114 1.DOC - A -

compute an ST deviation volume for the at least one electrode, based, at least in part, on the magnitude of ST deviation and the area factor.

Brief Description of the Drawings FIG. 1 shows an ECG waveform of a normal heart beat traced on a standard grid;

FIG. 2A shows an ECG waveform exhibiting ST elevation;

FIG. 2B shows an ECG waveform exhibiting ST depression;

FIG. 3A shows an array of electrodes applied to the front of a human torso; FIG. 3B shows an array of electrodes applied to the back of a human torso;

FIGs. 4A-B show examples of ST deviation volume (STDV) for a single electrode;

FIGs. 5A-B show examples of aggregate ST deviation volume for a plurality of electrodes; FIGs. 6A and 6B show, respectively, an anterior portion and a posterior portion of an exemplary BSM device for obtaining ECG data;

FIG. 6C shows an exemplary arrangement of electrodes into four regions; FIG. 7 is a flow chart illustrating a method for calculating aggregate STDV; FIG. 8 is a flow chart illustrating a method for diagnosing a patient; FIGs. 9-12 illustrate aggregate STDV values of patients with confirmed Ml or confirmed non-MI diagnoses;

FIG. 13-20 are three-dimensional illustrations of example cases exhibiting ST elevation and/or depression; and

FIG. 21 is a schematic illustration of an exemplary computer on which aspects of the invention may be implemented.

1840114 1.DOC DETAILED DESCRIPTION

This invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. In the claims, the use of "including," "comprising," "having," "containing," "involving," and variations thereof, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items. The Applicant has appreciated that BSM techniques may be enhanced by providing a method for quantifying the extent of cardiac injury based on data collected from an array of electrodes. This may enable a physician to select an appropriate treatment for a patient diagnosed with Ml based on the severity of the Ml. It may also be used to assess a patient's condition before and after a percutaneous coronary intervention (PCI) procedure. Compared to other imaging modalities such as angiogram, MRI, and echocardiogram, a BSM-based method for quantifying the extent of cardiac injury may be less expensive and more convenient.

The Applicant has further appreciated that data obtained from a BSM electrode array may have two aspects or dimensions: the areas affected, for example, as indicated by the distribution of electrodes detecting ST deviation, and the magnitudes of ST deviation detected by the individual electrodes. A measurement comprising only one of these two dimensions may not provide sufficient information. For example, a simple area count may reveal how wide spread the injury is, but may fail to indicate the severity of injury in the affected areas. Likewise, a measurement based solely on the magnitudes of ST deviation (e.g., taking the most severe deviation observed by a single electrode) may miss a mild but wide-spread injury.

In accordance with some embodiments of the invention, a new parameter, called ST deviation volume (STDV), is used to assess the extent of cardiac muscle injury. The STDV parameter combines both area and magnitude information. As its name suggests, the STDV of an individual electrode may be determined based on an area of the heart associated with the electrode and the magnitude of ST deviation detected by

1840114 1.DOC the electrode. For instance, the STDV of an electrode may be calculated by multiplying the magnitude of ST deviation detected by the electrode with an area factor associated with the electrode. As will be discussed in greater detail below, the magnitude of ST deviation may be scaled, or otherwise adjusted, based on the location of the electrode on the patient's torso and therefore the distance between the electrode and the heart. The area factor associated with the electrode may also be determined in a number of different ways, for example, by using the number of electrodes that are associated with the same region of the heart as the present electrode. In one embodiment, a first electrode that is associated with a densely populated region (i.e., a region of the heart to which many electrodes are associated) has a smaller area factor than a second electrode that is associated with a sparsely populated region (i.e., a region of the heart to which few electrodes are associated). Alternatively, each region of the heart may be projected to a region of the patient's torso, so that an area factor for a particular electrode may be determined using the density of electrodes in the region of the torso in which the particular electrode resides.

In some further embodiments, an aggregate STDV may be determined by considering STDV values obtained from a plurality of electrodes. For example, an aggregate STDV may be computed as the sum of all STDV values, both elevation and depression, obtained from all electrodes in an electrode array. In this case, the aggregate STDV may be referred to as a total STDV. Alternatively, an aggregate STDV may be computed as the sum of all STDV values obtained from electrodes detecting STDV elevation. In this case, the aggregate STDV may be referred to as a total ST elevation volume (total STEV). Similarly, an aggregate STDV may be computed as the sum of all STDV values obtained from electrodes detecting STDV depression. In this case, the aggregate STDV may be referred to as a total ST depression volume (total STDpV).

Under some circumstances, total STEV and total STDpV may be more useful than total STDV. For example, the Applicant has recognized that an area of ST elevation is often accompanied by a reciprocal area of ST depression on the opposite side of the torso. If a patient is diagnosed with STEMI₁ it may be more informative to compare the patient's total STEV against a database of total STEV values. Likewise, if

1840114 1.DOC a patient diagnosed with ischemia, it may be more informative to compare the patient's total STDpV against a database of total STDpV values.

The Applicant has also appreciated the need for a method by which a physician may interpret an aggregate STDV value. In accordance with some embodiments of the invention, aggregate STDV values from patients with confirmed diagnoses (Ml or non- Mi) are collected and stored in a database. The diagnoses may be obtained using a well-established method, such as testing for Troponin levels in the blood. In some embodiments, a diagnostic threshold for determining whether a patient is suffering from Ml may be obtained based on aggregate STDV values from both confirmed Ml and confirmed non-MI patients. In a further embodiment, the aggregate STDV values of confirmed Ml patients may be sorted, and bands representing the top/middle/bottom thirds may be identified. To diagnose a new patient, the aggregate STDV value of the new patient may be compared against the diagnostic threshold to determine whether the new patient suffers from Ml, and if so, to classify the new patient's condition as severe, medium, or mild, based on the top/middle/bottom bands. An appropriate treatment (e.g., aggressive vs. moderate) may then be selected based on the diagnosis and classification.

In some further embodiments, separate databases may be maintained for total STDV, total STEV, and/or total STDpV. These databases may be used for classifying patients with different diagnoses. For example, if the diagnosis is STEMI, then the patient's total STEV value may be compared against values in the total STEV database. Likewise, if the diagnosis is ischemia, then the patient's total STDpV value may be compared against values in the total STDpV database.

The Applicant has further appreciated that, since some non-MI conditions may also lead to ST elevation, it may be desirable to exclude from the database STDV values from non-MI patients suffering from those conditions. One such condition, left bundle branch block (LBBB), will be further discussed below.

It should be appreciated that, although some embodiments are summarized above, such examples are non-limiting. For example, the area factor used to compute STDV for an individual electrode may be obtained using another suitable method, without relying on the density of electrodes. Furthermore, the classification bands

1840114 1.DOC discussed above may correspond to halves, quarters, or some other breakdown, as opposed to thirds.

Turning to FIGs. 4A-B, examples of STDV for a single electrode are illustrated. As discussed above, STDV for a single electrode may be determined based on an ST deviation magnitude detected by the electrode and an area factor associated with the electrode. The ST deviation magnitude may be determined using any suitable technique, as the invention is not limited in this respect. For example, the ST deviation may be measured at any of the standard points such as the J point (also known as STO, the point at which the QRS complex meets the ST segment), ST60 (60 msec after STO), or ST80 (80 msec after STO).

In some embodiments, the area factor associated with the electrode may depend on the location of the electrode on the patient's torso. For example, the area factor may depend on the density of electrodes in the region of the torso in which the electrode is located. In some embodiments, the area factor of a first electrode in a densely populated region may be smaller than that of a second electrode in a sparsely populated region, because the first electrode monitors a smaller area of the heart compared to the second electrode. However, as mentioned above, it should be appreciated that the invention is not limited to any particular method for determining an area factor for an electrode. FIG. 4A represents the STDV of a first electrode that is detecting an ST elevation of 3 mm and is associated with an area factor of 1. As a result, the STDV for the first electrode is 3 mm. In this embodiment, the area factor is obtained by taking a ratio of the electrode density in the most dense region (denoted EDh) and the electrode density in the region of the electrode (denoted EDr). More particularly, the first electrode may be located in the most dense region, or in a region with the same density as the most dense region. Therefore, the area factor A is simply 1.

FIG. 4B represents the STDV of a second electrode that is detecting an ST elevation of 0.75 mm and is associated with an area factor of 4. The second electrode may be located in a region with lower density (e.g., 4 electrodes per dm²), compared to

1840114 1.DOC the region with the highest density (e.g., 16 electrodes per dm²). Thus, the area factor for the second electrode can be computed as:

A = EDh/EDr = \6/4 = 4.

As a result, the STDV for the second electrode is STDV = d * A = 0.75 * 4 = 3 mm, which is the same as the STDV for the first electrode, even though the first electrode is detecting ST elevation of a much higher magnitude than the second electrode.

It should be appreciated that, although the area factors in the examples shown in

FIGs 4A-B are ratios of densities and therefore unitless, the invention is not limited in this respect. An area factor may be computed in any suitable way, and may have any suitable unit as a result of the method by which it is computed. In general, an area factor provides information regarding the breadth of cardiac muscle injury, and it need not correspond to any physical measurement of area.

Similarly, the STDV of an electrode may also have any suitable unit. In the embodiments illustrated in FIGs. 4A and 4B, STDV has the same unit as ST deviation, because the former is a product of the latter with a unitless area factor. In other embodiments, however, STDV may have other units, or may be treated as a unitless quantity.

FIGs. 5A-B illustrate examples of total STDV for a plurality of electrodes. FIG.

5A shows eight columns, each representing STDV for one electrode. The height of each column represents the magnitude of ST elevation detected by the corresponding electrode. For example, column 510 has a height of 1.25, indicating that the electrode corresponding to column 510 detects an ST elevation of 1.25 mm. As shown in FIG.

5A, the eight corresponding electrodes detect various levels of ST elevation, ranging from 0 mm to 1.25 mm. Moreover, the eight electrodes may be located in the same region of the patient's torso, for example, in the most densely populated region, so that the area factor for each electrode is 1. Summing all of the STDV values, the total STDV for the eight electrodes in FIG. 5A is computed to be 3.75 mm.

FIG 5B also shows eight columns that correspond respectively to eight electrodes. The magnitudes of ST elevation detected by these eight electrodes range from 0.25 mm to 0.5 mm. For example, column 510 has a height of 0.5, indicating that the electrode corresponding to column 520 detects an ST elevation of 0.5 mm. As with

1840114 1.DOC FIG. 5A, each electrode is associated with an area factor of 1. As a result, the total STDV for the eight electrodes in FIG. 5B is also 3.75mm.

As shown in FIGs 5A-B, total STDV (or, in general, aggregate STDV) may provide a meaningful way of comparing a patient with a larger ST deviation that is only exhibited in a small area against another patient with a widespread but small ST deviation. For example, the data shown in FIG. 5A indicates a relatively severe ST deviation at one electrode, namely, the electrode corresponding to column 510. By contrast, the data shown in FIG. 5B indicates a relatively mild ST deviation of at most 0.5 mm across all eight electrodes. In other words, while the maximum deviation in FIG. 5A (1.25 mm) is much high than that in FIG. 5B (0.5 mm), the cardiac muscle injury is more widespread in FIG. 5B than it is in FIG. 5A. Therefore, the overall extent of injury may, in fact, be comparable in the two cases. In this way, an aggregate STDV parameter may allow a physician to assess more accurately the condition of a patient suffering from Ml, by comparing an aggregate STDV value from the patient against aggregate STDV values of patients with confirmed diagnoses.

Turning to FIG. 6A, an anterior portion 600a of an exemplary BSM device is shown, comprising an array of 65 electrodes. When the entire array is applied to a patient's torso, different electrode columns in the array may be located in different anatomical regions. For example, electrodes 1-7 may be located on the right hand side on the front of the patient's chest, whereas electrodes 56-58, V6, and 60-61 may be located under the patient's left arm. FIG. 6B shows a posterior portion 600b of the exemplary BSM device, comprising 16 electrodes. When applied to the patient, electrodes 62-71 may be located on the patient's back, with electrodes 62-65 to the left of the patient's spine and electrodes 68-71 to the right of the patient's spine. Electrodes 72-77 may be located under the patient's right arm.

In some embodiments, electrodes may be organized into different groups based on their respective locations on the patient's torso. This grouping may in turn determine whether and how the ST deviation data collected from each of the electrodes is processed and incorporated into an aggregate STDV value. In one embodiment, at least some electrodes of a BSM device may be divided into four regions: anterior, inferior, posterior, and right ventricle (RV). For example, in

1840114 1.DOC the BSM device of FIGs. 6A and 6B, electrodes 8, 18-21.V2, 23, 24, 28-32, V3, 34, 38- 43, V4, 48-52, V5, 56-58, and V6 may belong to the anterior region (shown as 610 and 612 in FIG. 6A); electrodes 7, 15-17, 25-27, 35-37, 45-47, 54, 55, 60, and 61 may belong to the inferior region 620; electrodes 1-6, 9-11, V1 , 13, 14, and 72-77 may belong to the RV region (shown as 630a in FIG. 6A and 630b in FIG. 6B); and electrodes 62-71 may belong to the posterior region 640. Electrodes in each of these regions may monitor a corresponding region of the heart as indicated by the name of the group. This arrangement is further illustrated in FIG. 6C, showing all electrodes from FIGs 6A and 6B grouped into four regions: ANT, INF, RV, and POST. As shown in FIGs. 6A-C, electrodes are more densely distributed in the anterior region compared to the posterior region. As discussed above, these densities of electrodes may be taken into account when computing aggregate STDV.

The Applicant has appreciated that, when applied to a patient's torso, electrodes in these different regions may be located at different distances from the heart. This may lead to different levels of signal attenuation from the heart to the body surface where the electrodes are attached. For example, electrodes in the anterior region maybe physically closer to the heart compared to electrodes in other regions, and therefore may have larger ECG morphologies. To compensate for this effect, an ST deviation threshold may be chosen for each of the regions, with a highest threshold being associated with the anterior region. For example, the anterior threshold may be 1.5 mm, the posterior threshold may be 0.5 mm, the inferior threshold may be 1.0 mm, and the RV threshold may be 0.9 mm.

Within each region, an ST elevation below the corresponding threshold may be considered normal. If an ST elevation above the corresponding threshold is observed, an adjusted (or exceedance) magnitude may be computed by subtracting the corresponding threshold from the raw magnitude. For example, if an anterior electrode detects an ST elevation of raw magnitude 2 mm, an adjusted magnitude of 0.5 mm (obtained by subtracting the anterior threshold of 1.5 mm) may be reported and used in the calculation of STDV. On the other hand, if a posterior electrode detects an ST elevation of raw magnitude 1.5 mm, an adjusted magnitude of 1.0 mm (obtained by

1840114 1.DOC subtracting the Posterior threshold of 0.5 mm) may be reported and used in the calculation of STDV.

ST depression may be computed similarly, by reporting only the magnitude of depression in excess of a threshold. For each region, the same threshold may be used as for ST elevation, or a different threshold may be chosen. For example, an anterior threshold for ST depression may be selected to be 1.0 mm, so that an ST depression of 1.5 mm from the anterior region may be reported as an adjusted ST depression of 0.5 mm.

It should be appreciated that, while the threshold values listed above may provide desirable adjustments that reflect different levels of signal attenuation, other suitable values may also be used. Also, different sets of thresholds may be determined for different patient populations. For example, diagnostic thresholds suitable for male patients may be slightly different from those suitable for female patients. Similarly, diagnostic thresholds may be adjusted according to age, weight, and/or other factors. Instead of, or in addition to, using thresholds to adjust ST deviation magnitudes, it may be beneficial to scale ST deviation magnitudes using various scaling factors. As with the thresholds, scaling factors may also be region dependent and may be selected to counteract the effect of different levels of signal attenuation. For example, ST deviation magnitudes from the Posterior region may be scaled up by a factor of 3, ST deviation magnitude from the Inferior region may be scaled up by a factor of 1.5, ST deviation magnitude from the RV region may be scaled up by a factor of 1.67, and ST deviation magnitudes from the anterior region may be unchanged (or scaled by a factor of 1). Selecting an appropriate scaling factor for a particular region may help to ensure that a desired weighting is given to ST deviations from the region when calculating an aggregate STDV. However, it should be appreciated that the invention is not limited to the method by which scaling factors are determined, nor to the use of scaling factors. Also, the ST deviation magnitudes being scaled may be raw measurements from the electrodes, or they may be already adjusted using regional thresholds.

In some embodiments, scaling factors may be determined by taking a ratio of regional thresholds. For example, the scaling factor of a particular region may be a ratio of the anterior threshold and the threshold for the particular region. In the example

1840114 1.D0C described above, the anterior threshold (denoted RTa) may be 1.5 mm, and the inferior threshold (RTi) may be 1.0 mm. Thus, the scaling factor for the inferior region may be calculated as:

S = RTa/ RTi = 1.5/1 = 1.5. If an inferior electrode is detecting an ST deviation of 0.5 mm, a scaled ST deviation magnitude of 0.75 (obtained by multiplying 0.5 mm by the factor of 1.5) may be reported and used in the calculation of STDV. Scaling ST deviation magnitudes in this way may give values from other regions equal weighting as those from the anterior region.

As mentioned above, the techniques of adjusting and scaling may be used alone or in combination. In accordance with some embodiments, STDV for a single electrode is calculated by first adjusting a raw ST deviation magnitude using a threshold and thereafter scaling the adjusted ST deviation magnitude using a scaling factor. Such an embodiment is described below in connection with FIG. 7, which illustrates a method for computing total STEV. Referring to FIG. 7, the process begins at step 700 by setting a variable TSTEV to zero. This variable will be used as an accumulator for computing the total STEV. After this initial step, the process enters into a loop to process ECG data obtained from a plurality of electrodes. At step 710, an electrode that has not yet been processed is selected, and ECG data from that electrode is obtained from a suitable source. For example, the ECG data may be obtained in real time from a patient, or it may be retrieved from a memory device storing previously obtained ECG data. At step 720, it is determined whether the selected electrode exhibits ST elevation. If not, the selected electrode is skipped, and the process continues to step 780. If, on the other hand, the selected electrode does exhibit ST elevation, the process is broken up into two sub- processes 721 and 722, which may be executed in parallel or interleaved in any suitable manner. At step 730 of sub-process 721, a magnitude d of ST elevation is determined for the selected electrode. In sub-process 722, a region associated with the selected electrode is determined at step 735. For example, the region may be anterior, posterior, inferior, or RV. After step 735, the sub-process is further divided into two sub-processes, 736 and 737, which again may be executed in parallel or interleaved in any suitable manner. At step 740 of sub-process 736, an area factor A associated with

1840114 1.DOC the selected electrode is determined, for example, by taking a ratio of the electrode density in the most dense region (EDh) and the electrode density in the region of the selected electrode (EDr). Alternatively, a pre-computed area factor may simply be retrieved. In sub-process 737, a regional threshold RT is determined for the region of the selected electrode at step 745. Thereafter, at step 750, a scaling factor S for the region is determined, for example, by taking a ratio of the threshold for the anterior region (RTa) and the threshold for the region of the selected electrode (RT). Alternatively, a pre-computed scaling factor may be retrieved.

Once steps 730, 740, and 750 have been completed, the process proceeds to step 760, where STEV for the selected electrode is computed as follows: if d is less than or equal to RT, then STEV = 0; otherwise,

STEV = (d - RT) * S * A.

At step 770, this STEV is added to the accumulator TSTEV. After that, the process moves to the decision block at step 780 to determine if there is at least one more electrode to be processed. If so, the process loops back to step 710; otherwise, the total STEV is reported and the process ends.

It is to be appreciated that many variations of the process shown in FIG. 7 are also within the scope and spirit of the invention. For example, the process of FIG. 7 can be modified to compute total STDpV, instead of total STEV. To that end, step 720 may be modified so that an electrode is processed if and only if it exhibits ST depression. Step 730 may be modified so that the magnitude d is a magnitude of the observed ST depression, as a positive quantity. Similarly, the process of FIG. 7 can be modified to compute total STDV. For example, step 720 may simply be eliminated so that all electrodes are processed, and steps 730 and 760 may be modified so that d is the magnitude of elevation if the electrode is exhibiting ST elevation, and is the magnitude of depression if the electrode is exhibiting ST depression. In both cases, d, being a magnitude, is a positive quantity.

As discussed above, some embodiments of the invention also provide a method by which a physician may interpret an aggregate STDV value. In one such embodiment, total STEV values from patients with confirmed diagnoses (Ml or non-MI) are collected and stored in a database. The diagnoses may be obtained using a well-

1840114 1.DOC established method, such as testing for Troponin levels in the blood. The total STEV values of confirmed Ml patients may be sorted, and various band thresholds may be identified. For example, a threshold for diagnosing whether a patient is suffering from Ml may be determined. In addition, thresholds representing the top/middle/bottom thirds of Ml may also be determined. An exemplary method for diagnosing a new patient using these thresholds will now be discussed in connection with FIG. 8.

FIG. 8 shows a process for determining whether a patient suffers from Ml and for selecting an appropriate treatment based on the diagnosis. Particularly, the total STEV value of the patient is compared against a diagnostic threshold to determine whether the patient suffers from Ml. If the conclusion is yes, the total STEV value of the patient is further compared against one or more other diagnostic thresholds to classify the patient's condition as severe, medium, or mild. An appropriate treatment (e.g., aggressive vs. moderate) may then be selected based on the diagnosis and classification. At step 810, a patient's total STEV is obtained, for example, by calculating it from the patient's ECG data or by retrieving it from a database. At step 820, it is determined whether the patient's total STEV exceeds the Ml threshold. If the conclusion is yes, then the patient is determined to be suffering from Ml and the process proceeds to step 830. Otherwise, the patient is determined not to be suffering from Ml and the process ends. At step 830, it is determined whether the patient's total STEV exceeds the top third threshold. If the conclusion is yes, then the patient is determined to be suffering from severe Ml, and aggressive treatment is recommended at step 835 and the process ends thereafter. Otherwise, it is determined at step 840 whether the patient's total STEV exceeds the middle third threshold. If the conclusion is yes, then the patient is determined to be suffering from medium Ml. In that case, moderate treatment is recommended at step 845, and thereafter the process ends. Otherwise, the patient is determined to be suffering from mild Ml, and the process continues to step 850, where it is recommended that the patient continue to be monitored.

Turning now to FIGs. 9-12, methods for building a database comprising aggregate STDV values from patients with confirmed diagnoses (Ml or non-MI) and for determining various diagnostic thresholds are described in greater detail.

1840114 1.DOC The embodiments illustrated in FIGs 9-12 are based on a database containing approximately 400 cases. The 400 cases contain approximately 50% confirmed Ml and 50% confirmed non-MI cases. Approximately two thirds of the data is from male patients, and one third is from female patients. Furthermore, the database has a proportion of cases with other conditions, such as LBBB with and without Ml, early repolarization, left ventricular hypertrophy (LVH), pericarditis, and right bundle branch block (RBBB).

It should be appreciated that the database is not limited to the number and composition of cases described in this example. For example, the database is not limited to any particular proportions of patients from different demographic groups and/or with different medical conditions. Furthermore, even though STDV is treated as a unitless quantity in this example, a comparison between STDV values of different patients is still meaningful, because the STDV values are obtained in a consistent manner across all patients. Each of the cases in the database has an Ml or a non-MI diagnosis that is confirmed by Troponin testing. For each case, two versions of total STEV were calculated for each of four regions, anterior, posterior, inferior, and RV. In the first version, ST elevation was measured with respect to the isoelectric line (or baseline). In the second version, ST elevation was measured with respect to the following thresholds (hereinafter STO Filter thresholds): 1.5 for anterior, 0.5 for posterior, 1 for inferior, and 0.9 for RV. Similarly, two versions of total STDpV were calculated, one with respect to the isoelectric line and another with respect to the STO Filter thresholds.

As discussed earlier, it may be desirable that the contributions of the four regions are weighted before they are incorporated into an aggregate. Thus, in the illustrated embodiments, both area factors and scaling factors are used. Specifically, the area factors are: 1 for anterior, inferior and RV, and 4 for posterior. The scaling factors are: 1 for anterior, 1.5 for inferior, 1.67 for RV, and 3 for posterior.

In FIG. 9, the number of cases is plotted against total STEV, where total STEV is computed from ST elevation measured with respect to baseline. The two curves represent, respectively, data from confirmed Ml patients and data from confirmed non- MI patients. As shown, there are roughly the same number of Ml and non-MI patients

1840114 1.DOC with a total STEV value of 50. As a result, it may be difficult to determine, solely based on total STEV computed with respect to baseline, whether a patient is suffering from Ml. A much clearer separation between Ml and non-MI is observed when the STO Filter thresholds are adopted. FIG. 10 shows the number of cases being plotted against total STEV with respect to STO Filter thresholds. As shown, very few non-MI patients exhibit a total STEV value of 25 or higher with respect to STO Filter thresholds. This, therefore, demonstrates that the chosen STO Filter thresholds have been correctly chosen as they open up clear separation between the Ml and non-MI cases. Furthermore, it may be reliable to use 25 as a diagnostic threshold for determining whether a patient is suffering from Ml. The data plotted in FIG. 10 is further summarized in Table 1 below. Cutoff points for both quartiles and thirds are given. As can be deduced from the table, only a quarter of all non-MI patients exhibit a total STEV value of 0.8 or higher in this example. By contrast, three quarters of all Ml patients exhibit a total STEV value of 6.5 or higher.

Table 1. Comparison of Total STEV

In this example, an even clearer separation between Ml and non-MI is observed when LBBB cases are removed from the data from which the non-MI curve was generated. LBBB patients may exhibit ST elevation in the anterior region, even if they are not suffering from Ml. Therefore, when LBBB cases are excluded from the non-MI portion of the database, the separation between the Ml and non-MI curves may become even larger. FIG. 11 shows the number of cases being plotted against total STEV with

1840114 1.DOC respect to STO Filter thresholds, with LBBB patient data excluded from non-MI data. As shown, the non-MI curve is now almost parallel with the Y axis and very few non-MI patients exhibit a total STEV value of 15 or higher with respect to STO Filter thresholds.

Another condition, called early repolarization, is also known to be associated with ST elevation. The Applicant has recognized that removing early repolarization cases from the database may not alter the shapes of the curves noticeably. The Applicant has further recognized that leaving early repolarization in the database may provide further information. For example, if a patient is diagnosed with early repolarization and exhibits total STEV in the lower third of confirmed Ml, it may be acceptable to assume that the patient is not suffering from Ml. However, if the total STEV of the patient is in the middle third, then Ml is still suspected and more evidence may be needed.

ST depression data may be collected and plotted in a similar way as ST elevation. FIG. 12 shows Ml and non-MI curves for both total STEV (as positive quantities) and total STDpV (as negative quantities). As can be seen from FIG. 12, there is good symmetry between STEV and STDpV. Table 2 further summarizes the total STDpV data plotted in FIG. 12, with cutoff points for both quartiles and thirds. Again, a significant difference between Ml and non-MI is demonstrated. Only a quarter of all non-MI patients exhibit a total STDpV value of 0.4 or higher. By contrast, three quarters of all Ml patients exhibit a total STEV value of 0.5 or higher.

Table 2. Comparison of Total STDpV

1840114 1.DOC FIGs. 13-20 are three-dimensional representations of exemplary cases. FIGs. 13, 15, and 17 show, respectively, examples with total STEV in the low, middle, and upper thirds of confirmed Ml cases, where the ST deviation magnitudes are taken with respect to the isoelectric line. FIGs. 14, 16, and 18 show the same cases, but with ST deviation magnitudes taken with respect to the STO Filter thresholds as described above. In particular, FIGs. 13 and 14 illustrate a case with relatively mild diffuse elevation (0.82 mm in the posterior region), and the corresponding total STEV value is around 8, which is in the lower third. FIGs. 15 and 16 illustrate a case with moderate diffuse elevation (2 mm in the inferior region), and the total STEV value is around 20, which is in the middle third. FIGs. 17 and 18 illustrate a case with relatively severe diffuse elevation (5.5 mm in the anterior region), and the total STEV values is around 56, which is in the upper third.

As can be seen from these figures, total STEV values may be valuable to a physician. For example, the case shown in FIGs. 15 and 16 may appear severe because the ST deviation is widespread. However, total STEV values suggest it is less severe than the case of FIGs. 17 and 18, which exhibits very severe ST elevation concentrated in the anterior region.

FIGs. 19 and 20 show a case with early repolarization, where the ST deviation magnitudes are taken, respectively, with respect to the isoelectric line and with respect to the STO thresholds. This case shows relatively mild compact elevation (2.44 mm in the anterior region), and the total STEV value is 7, which is in the lower third. As described above, if the patient is diagnosed with early repolarization, it may be acceptable to rule out Ml when total STEV is in the lower third, but more evidence may need to be collected when total STEV is in the middle third. The above-described embodiments of the invention can be implemented in any of numerous ways. For example, the embodiments may be implemented using hardware, software or a combination thereof. When implemented in software, the software code can be executed on any suitable processor or collection of processors, whether provided in a single computer or distributed among multiple computers.

1840114 1.DOC Also, the various methods or processes outlined herein may be coded as software that is executable on one or more processors that employ any one of a variety of operating systems or platforms.

In this respect, the invention may be embodied as a computer readable medium or multiple computer readable media (e.g., a computer memory, one or more floppy discs, compact discs, optical discs, magnetic tapes, flash memories, circuit configurations in Field Programmable Gate Arrays or other semiconductor devices, or other tangible computer storage medium) encoded with one or more programs that, when executed on one or more computers or other processors, perform methods that implement the various embodiments of the invention discussed above. The computer readable medium or media can be transportable, such that the program or programs stored thereon can be loaded onto one or more different computers or other processors to implement various aspects of the present invention as discussed above.

FIG. 21 is a schematic illustration of an exemplary computer 2100 on which aspects of the invention may be implemented. The computer 2100 includes a processor or processing unit 2101 and a memory 2102 that can include both volatile and non-volatile memory. The computer 2100 also includes storage 2105 (e.g., one or more disk drives) in addition to the system memory 2102. The memory 2102 can store one or more instructions to program the processing unit 2101 to perform any of the functions described herein. As mentioned above, the reference herein to a computer can include any device having a programmed processor, including a rack-mounted computer, a desktop computer, a laptop computer, a tablet computer or any of numerous devices that may not generally be regarded as a computer, which include a programmed processor (e.g., a PDA, an MP3 Player, a mobile telephone, wireless headphones, etc.).

Computer 2100 may have one or more input and output devices, such as devices 2106 and 2107 illustrated in FIG. 21. These devices can be used, among other things, to present a user interface. Examples of output devices that can be used to provide a user interface include printers or display screens for visual presentation of output and speakers or other sound generating devices for audible presentation of output. Examples of input devices that can be used for a user interface include

1840114 1.DOC keyboards, and pointing devices, such as mice, touch pads, and digitizing tablets. As another example, a computer may receive input information through speech recognition or in other audible format.

Computer 2100 may also comprise network interface cards (e.g., 2118a-c) to enable communication via various networks (e.g., 2119a-c). Examples of networks include a local area network or a wide area network, such as an enterprise network or the Internet. Such networks may be based on any suitable technology and may operate according to any suitable protocol and may include wireless networks, wired networks or fiber optic networks. Various aspects of the invention may be used alone, in combination, or in a variety of arrangements not specifically discussed in the embodiments described in the foregoing. For example, aspects described in one embodiment may be combined in any manner with aspects described in other embodiments.

Having thus described several aspects of at least one embodiment of this invention, it is to be appreciated that various alterations, modifications, and improvements will readily occur to those skilled in the art. Such alterations, modifications, and improvements are intended to be within the spirit and scope of the invention. Accordingly, the foregoing description and drawings are by way of example only. What is claimed is:

1840114 1.DOC

Claims

1. A computer-implemented method for quantifying an extent of cardiac muscle injury, comprising: determining a magnitude of ST deviation based on electrocardiographic data obtained from at least one electrode in an electrocardiograph, the at least one electrode being associated with at least one region of a heart; determining an area factor for the at least one electrode, the area factor being associated with the at least one region; computing an ST deviation volume for the at least one electrode, based, at least in part, on the magnitude of ST deviation and the area factor; and storing the ST deviation volume in a computer-readable storage medium.

2. The method of claim 1 , wherein an anterior region has a first area factor and a posterior region has a second area factor, and wherein the first area factor is smaller than the second area factor.

3. The method of claim 1 , wherein the area factor is chosen based on a size of the at least one region and a number of electrodes that are associated with the at least one region.

4. The method of claim 1 , further comprising: displaying a representation of the ST deviation volume for the at least one electrode.

5. The method of claim 1 , wherein the magnitude of ST deviation is a scaled magnitude of ST deviation obtained, at least partially, by: determining an unsealed magnitude of ST deviation based on the electrocardiographic data obtained from the at least one electrode; determining a scaling factor associated with the at least one electrode; and computing the scaled magnitude of ST deviation by, at least partially, scaling the unsealed magnitude of ST deviation using the scaling factor.

1840114 1.DOC

6. The method of claim 5, wherein an anterior region has a first scaling factor and a posterior region has a second scaling factor, and wherein the first scaling factor is smaller than the second scaling factor.

7. The method of claim 1 , wherein the magnitude of ST deviation is an adjusted magnitude of ST deviation obtained, at least partially, by: determining an unadjusted magnitude of ST deviation based on the electrocardiographic data obtained from the at least one electrode; determining a threshold associated with the at least one electrode; and computing the adjusted magnitude of ST deviation by, at least partially, subtracting the threshold from the unadjusted magnitude of ST deviation.

8. The method of claim 7, wherein an anterior region has a first threshold and a posterior region has a second threshold, and wherein the first threshold is larger than the second threshold.

9. The method of claim 1 , wherein the electrocardiograph comprises a plurality of electrodes, and wherein the method further comprises: computing an ST deviation volume for each of the plurality of electrodes; and computing an aggregate ST deviation volume based, at least in part, on the ST deviation volume for each of the plurality of electrodes.

10. The method of claim 9, wherein the aggregate ST deviation volume is computed by summing the ST deviation volume for each of the plurality of electrodes.

11. The method of claim 1 , wherein the electrocardiograph comprises a plurality of electrodes, and wherein the method further comprises: computing an ST deviation volume for each of the plurality of electrodes; and computing an aggregate ST elevation volume based, at least in part, on the ST deviation volume for each of the plurality of electrodes detecting ST elevation.

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12. The method of claim 1 1 , wherein the aggregate ST elevation volume is computed by summing the ST deviation volume for each of the plurality of electrodes detecting ST elevation.

13. The method of claim 1 , wherein the electrocardiograph comprises a plurality of electrodes, and wherein the method further comprises: computing an ST deviation volume for each of the plurality of electrodes; and computing an aggregate ST depression volume based, at least in part, on the ST deviation volume for each of the plurality of electrodes detecting ST depression.

14. The method of claim 13, wherein the aggregate ST depression volume is computed by summing the ST deviation volume for each of the plurality of electrodes detecting ST depression.

15. A device comprising: a computer-readable storage medium encoded with computer-executable instructions that, when executed, carry out a method for quantifying an extent of cardiac muscle injury, the method comprising determining a magnitude of ST deviation based on electrocardiographic data obtained from at least one electrode in an electrocardiograph, the at least one electrode being associated with at least one region of a heart; determining an area factor for the at least one electrode, the area factor being associated with the at least one region; and computing an ST deviation volume for the at least one electrode, based, at least in part, on the magnitude of ST deviation and the area factor.

16. The device of claim 15, wherein an anterior region has a first area factor and a posterior region has a second area factor, and wherein the first area factor is smaller than the second area factor.

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17. The device of claim 15, wherein the area factor is chosen based on a size of the at least one region and a number of electrodes that are associated with the at least one region.

18. The device of claim 16, wherein the magnitude of ST deviation is a scaled magnitude of ST deviation obtained, at least partially, by: determining an unsealed magnitude of ST deviation based on the electrocardiographic data obtained from the at least one electrode; determining a scaling factor associated with the at least one electrode; and computing the scaled magnitude of ST deviation by, at least partially, scaling the initial magnitude of ST deviation using the scaling factor.

19. The device of claim 18, wherein an anterior region has a first scaling factor and a posterior region has a second scaling factor, and wherein the first scaling factor is smaller than the second scaling factor.

20. The device of claim 15, wherein the magnitude of ST deviation is an adjusted magnitude of ST deviation obtained, at least partially, by: determining an unadjusted magnitude of ST deviation based on the electrocardiographic data obtained from the at least one electrode; determining a threshold associated with the at least one electrode; and computing the adjusted magnitude of ST deviation by, at least partially, subtracting the threshold from the unadjusted magnitude of ST deviation.

21. The device of claim 20, wherein an anterior region has a first threshold and a posterior region has a second threshold, and wherein the first threshold is larger than the second threshold.

22. The device of claim 15, wherein the electrocardiograph comprises a plurality of electrodes, and wherein the method further comprises: computing an ST deviation volume for each of the plurality of electrodes; and

1840114 1.DOC computing an aggregate ST deviation volume based, at least in part, on the ST deviation volume for each of the plurality of electrodes.

23. The device of claim 22, wherein the aggregate ST deviation volume is computed by summing the ST deviation volume for each of the plurality of electrodes.

24. The device of claim 15, wherein the electrocardiograph comprises a plurality of electrodes, and wherein the method further comprises: computing an ST deviation volume for each of the plurality of electrodes; and computing an aggregate ST elevation volume based, at least in part, on the ST deviation volume for each of the plurality of electrodes detecting ST elevation.

25. The device of claim 24, wherein the aggregate ST elevation volume is computed by summing the ST deviation volume for each of the plurality of electrodes detecting ST elevation.

26. The device of claim 15, wherein the electrocardiograph comprises a plurality of electrodes, and wherein the method further comprises: computing an ST deviation volume for each of the plurality of electrodes; and computing an aggregate ST depression volume based, at least in part, on the ST deviation volume for each of the plurality of electrodes detecting ST depression.

27. The device of claim 26, wherein the aggregate ST depression volume is computed by summing the ST deviation volume for each of the plurality of electrodes detecting ST depression.

28. A method for diagnosing a patient based on aggregate ST deviation volume, the method comprising: obtaining an aggregate ST deviation volume of the patient based on magnitude and area information collected from an array of electrodes applied to the patient;

1840114_1.DOC retrieving, from a computer-readable storage medium, aggregate ST deviation volume data from a plurality of patients with confirmed diagnoses; obtaining one or more diagnostic thresholds using the aggregate ST deviation volume data; and comparing the aggregate ST deviation volume of the patient against the diagnostic thresholds.

29. The method of claim 28, wherein the diagnostic thresholds comprise a first diagnostic threshold for determining whether the patient is suffering from myocardial infarction (Ml), and wherein the first threshold is obtained based on first aggregate ST deviation volume data from confirmed Ml patients and second aggregate ST deviation volume data from confirmed non-MI patients.

30. The method of claim 29, wherein third aggregate ST deviation volume data from patients suffering from a condition other than Ml are excluded from the second aggregate ST deviation volume data.

31. The method of claim 30, wherein the condition other than Ml is left bundle branch block.

32. The method of claim 28, further comprising selecting a treatment for the patient based on a result of comparing the aggregate ST deviation volume of the patient against the diagnostic thresholds.

33. A system for quantifying an extent of cardiac muscle injury based on electrographic data obtained from a patient, the system comprising one or more processors programmed to: determine a magnitude of ST deviation based on electrocardiographic data obtained from at least one electrode applied to the patient, the at least one electrode being associated with at least one region of a heart;

1840114 1.DOC determine an area factor for the at least one electrode, the area factor being associated with the at least one region; and compute an ST deviation volume for the at least one electrode, based, at least in part, on the magnitude of ST deviation and the area factor.

34. The system of claim 33, wherein the magnitude of ST deviation is a scaled magnitude of ST deviation, and wherein the one or more processors are further programmed to: determine an unsealed magnitude of ST deviation based on the electrocardiographic data obtained from the at least one electrode; determine a scaling factor associated with the at least one electrode; and compute the scaled magnitude of ST deviation by, at least partially, scaling the unsealed magnitude of ST deviation using the scaling factor.

35. The system of claim 33, wherein the magnitude of ST deviation is an adjusted magnitude of ST deviation, and wherein the one or more processors are further programmed to: determine an unadjusted magnitude of ST deviation based on the electrocardiographic data obtained from the at least one electrode; determine a threshold associated with the at least one electrode; and compute the adjusted magnitude of ST deviation by, at least partially, subtracting the threshold from the unadjusted magnitude of ST deviation.

36. The system of claim 33, wherein the system further comprises a plurality of electrodes applied to the patient, and wherein the one or more processors are further programmed to: compute an ST deviation volume for each of the plurality of electrodes; and compute an aggregate ST deviation volume of the patient based, at least in part, on the ST deviation volume for each of the plurality of electrodes.

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37. The system of claim 36, wherein the one or more processors are further programmed to: compare the aggregate ST deviation volume of the patient against one or more diagnostic thresholds obtained using aggregate ST deviation volume data from a plurality of patients with confirmed diagnoses.

38. The system of claim 37, wherein the diagnostic thresholds comprise a first diagnostic threshold for determining whether the patient is suffering from myocardial infarction (Ml), and wherein the first threshold is obtained based on first aggregate ST deviation volume data from confirmed Ml patients and second aggregate ST deviation volume data from confirmed non-MI patients.

39. The system of claim 37, wherein the one or more processors are further programmed to: select a treatment for the patient based on a result of comparing the aggregate

ST deviation volume of the patient against the one or more diagnostic thresholds.

40. A system for quantifying an extent of cardiac muscle injury based on electrographic data obtained from a plurality of electrodes positioned on a patient in a thoracic region, the plurality of electrodes forming an array that covers a substantial portion of the thoracic region, the system comprising one or more processors programmed to: determine, for each of the plurality of electrodes, a raw magnitude of ST deviation based on the electrocardiographic data obtained from the each of the plurality of electrodes; determine, for each of the plurality of electrodes, an area factor, a threshold, and a scaling factor; compute, for each of the plurality of electrodes, a modified magnitude of ST deviation using the threshold and the scaling factor for the each of the plurality of electrodes;

1840114 1 DOC compute, for each of the plurality of electrodes, an ST deviation volume based, at least in part, on the modified magnitude of ST deviation and the area factor for the each of the plurality of electrodes; compute an aggregate ST deviation volume of the patient based, at least in part, on the ST deviation volume for each of the plurality of electrodes.

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