WO2007134289A2

WO2007134289A2 - Methods and apparatus for detecting fractionated conduction delay with an ecg

Info

Publication number: WO2007134289A2
Application number: PCT/US2007/068879
Authority: WO
Inventors: Li Zhang
Original assignee: Ihc Intellectual Asset Management Llc
Priority date: 2006-05-15
Filing date: 2007-05-14
Publication date: 2007-11-22
Also published as: WO2007134289A3

Abstract

The present disclosure provides methods and apparatus useful in the diagnosis of cardiomyopathies. The methods and apparatus may be particularly useful in the diagnosis of arrhythmogenic right ventricular dysplasia (ARVD) and Brugada syndrome (BrS). Some embodiments of the methods and apparatus include an electrode array with many electrodes that can be localized in front of or over a particular area of interest of the heart. The use of many local electrodes central or adjacent to the particular area of interest greatly increases the sensitivity of ECG to disease markers and increases the chances of early detection.

Description

TITLE

METHODS AND APPARATUS FOR DETECTING FRACTIONATED CONDUCTION DELAY WITH AN ECG

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit under 35 U.S. C. § 119(e) of U.S. Provisional Patent Application No. 60/747,249, filed May 15, 2006, which is incorporated, in its entirety, by this reference.

BACKGROUND

The present invention relates to electrocardiography and, more particularly, to methods and apparatus for analyzing a portion of an electrocardiographic signal for fractionated conduction delays.

Arrhythmogenic right ventricular dysplasia (ARVD) and Brugada syndrome (BrS) are complex cardiomyopathies. In typical cases, patients experience palpitations and recurrent syncope due to right ventricular tachycardia. The pathological process principally affects the right ventricular free wall with gradual myocardial degeneration (B) and fibrofatty infiltration (A), which results in the regional dilatation and global right ventricular dysfunction and failure. At present, most patients are brought to medical attention by the onset of ventricular arrhythmias, cardiac arrest or sudden death. At the time of diagnosis, many are already in the advanced stages, or sudden death is their first/last symptom, suggesting the ARVD, in its early stages, is largely concealed. Although symptoms can occur at any age, cardiac events often strike during the adolescent and young adult years. Rapid body development, hormonal influx, and increased physical activities may contribute to a speedy progression of the disease, and therefore trigger the onset of symptoms. Without a timely diagnosis, many young people with this condition are left untreated and unprotected from life-threatening cardiac events. Consequently, ARVD is one of the most common causes of sudden death in young people and sportsmen.

Much effort has therefore been devoted to identification of early stage of ARVD development in order to improve the early diagnosis. Identification of mild cases of ARVD, especially in childhood before the disease advanced to the stage of overt arrhythmogenic right ventricular cardiomyopathy, will clearly lead to early detection and a better prognosis. Early detection and identification of ARVD, however, remains a significant clinical challenge since routine clinical examination is typically normal and patients may have no complaint other than mild palpitations. The focus of such efforts has been on the use of electrocardiograms (ECG) to identify and detect markers of ARVD at an early stage.

Accordingly, there is a need in the art to develop methods for early detection and identification of fractionated conduction delays including LPs, VLPs, epsilon waves and coved ST elevations in ECG applications.

SUMMARY

The invention described herein may address some of the above-described deficiencies and others. Generally, the present invention relates to methods and systems for reliably detecting and identifying the presence or absence of a fractionated conduction delay (e.g. LPs, epsilon waves, and coved ST elevation) in a patient's ECG.

One aspect of the invention relates to a portable ECG electrode array adapted to be connected to the skin surface of a subject. The electrode array may comprise a plurality of unipolar precordial electrodes arranged in a fixed two-dimensional array (FRMZ-I Precordial Leads Array, Fig. 4). In one embodiment, the plurality of unipolar precordial electrodes is configured to detect fractionated conduction delays. In another embodiment, the plurality of unipolar precordial electrodes is sufficient in number and size to detect epsilon waves, late potentials, and coved ST elevation associated with a myocardial defect of a subject. In yet another embodiment, the array comprises a rectangular array of rows and columns of the unipolar precordial electrodes, wherein the number of rows and columns is within one unit of each another. In some embodiments, the number of rows and columns is equal.

In another embodiment, the array comprises a rectangular array of rows and columns of the unipolar precordial electrodes arranged in a tight pattern approximately the size of a human heart. In a particular embodiment, the array comprises fewer than thirty-two unipolar precordial electrodes. In another embodiment, the array comprises nine or more unipolar precordial electrodes arranged in an array comprising at least three aligned columns and three aligned

2 REPLACEMENT SHEET rows. In yet embodiment, the array comprises six or more unipolar precordial electrodes arranged in at least three columns and two rows. In still another embodiment, the array comprises four unipolar precordial electrodes arranged in two columns and two rows. According to another embodiment of the invention, the unipolar precordial electrodes are positioned substantially equidistant from each other. In one embodiment, the distance between the core (10 mm) of each electrode in the array ranges between about 20 and 30 mm.

In another embodiment, at least a portion of the array is positioned directly in front of a target region such as an expected myocardial defect area of the subject. The defect area may be in front of the right ventricular outflow tract (RVOT), the right ventricular inflow tract (RVIT), or the left ventricular wall of the subject. In some embodiments, at least a portion of the array is positioned in front of the right ventricular outflow tract (RVOT) of the subject. In other embodiments, all of the electrodes of the array are positioned over the right ventricular outflow tract (RVOT) of the subject. In one embodiment, the array circumscribes the right ventricular outflow tract (RVOT) of the subject. The array may be positioned adjacent to the right ventricular outflow tract (RVOT) of the subject.

One aspect of the invention relates to an ECG electrode array patch. The patch comprises a plurality of unipolar precordial electrodes disposed in an adhesive patch and configured to detect fractionated conduction delay originating from an RVOT region of a subject heart. In one embodiment, the adhesive patch comprises a geometric shape, and the density of the unipolar precordial electrodes disposed in the adhesive patch is at least six electrodes per 150 cm². In another embodiment, the density of the unipolar precordial electrodes disposed in the adhesive patch is at least six electrodes per 108.8 cm². In yet another embodiment, the density of the unipolar precordial electrodes disposed in the adhesive patch is at least six electrodes per 86.25 cm².

In one embodiment of the present invention, the adhesive patch comprises a geometric shape selected from the group consisting of: circle, rectangle, square, triangle, pentagon, hexagon, heptagon, octagon, nonagon, and decagon.

One embodiment of the invention provides an ECG electrode array patch comprising a plurality of unipolar precordial electrodes configured to be attached to the skin surface of a subject on an adhesive patch and arranged in a rectangular array. The adhesive patch may be substantially the same size as an RVOT region of a human heart. In some embodiments, the adhesive patch is sized to cover an RVOT human heart region, from IC2-V1, sternum, and IC2-V2 at a second intercostal space level, to corresponding positions at a third intercostal level, IC3-V1 and IC3- V2, respectively

In some embodiments, the rectangular array comprises as least six ECG electrodes arranged in at least three columns and at least two rows. The rectangular array may comprise as least nine ECG electrodes arranged in at least three columns and at least three rows.

According to one embodiment of the invention, the plurality of unipolar precordial electrodes comprises at least six electrodes and a maximum distance between any two electrodes is about 67 mm. The plurality of unipolar precordial electrodes may comprise at least six electrodes and a maximum distance between any two electrodes is about 45 mm. In some embodiments, the plurality of unipolar precordial electrodes comprises at least nine electrodes and a maximum distance between any two electrodes is about 85 mm. The plurality of unipolar precordial electrodes may comprise at least nine electrodes and a maximum distance between any two electrodes is about 56.5 mm. The adhesive patch may be transparent. Some embodiments of the rectangular array comprise six ECG electrodes arranged in three columns and two rows, and each electrode is connected to an associated precordial lead of a standard ECG machine. The rectangular array may comprise six ECG electrodes arranged in three columns and two rows, and each electrode may be connected to an associated precordial lead of a twelve-lead Holter ECG system. In one embodiment, the rectangular array comprises six ECG electrodes arranged in three columns and two rows, and each electrode is connected to an associated unipolar lead of an SAECG system.

One aspect provides an apparatus comprising an ECG system. The ECG system comprises a plurality of unipolar precordial electrodes arranged contiguously in a fixed coplanar two-dimensional array in sufficient number and size to detect low voltage ventricular late potentials associated with a myocardial defect of a subject, and an ECG recorder comprising leads connected to the plurality of unipolar precordial electrodes. The plurality of unipolar precordial electrodes may be paired with a posterior electrode arranged opposite of the plurality of unipolar precordial leads. The system may further comprise a pair of horizontally spaced electrodes for arrangement at opposite sides of the subject, a pair of vertically spaced electrodes for arrangement above and below a heart of the subject, and a ground electrode. One aspect provides a method of generating an ECG. The method comprises arranging at least four unipolar precordial electrodes on a subject's chest in front of the target region (which may be, for example, the RVOT region), arranging additional electrodes at other locations of the subject, connecting the electrodes to leads of an ECG machine, receiving signals from the electrodes, processing the received signals, and detecting fractionated conduction delays in the received signals. In one embodiment, detecting fractionated conduction delays comprises detecting epsilon waves. Detecting fractionated conduction delays may comprise detecting late potentials. Detecting fractionated conduction delays may comprise detecting coved ST elevation. In one embodiment, arranging at least four unipolar precordial electrodes comprises placing a patch comprising at least four, or at least six, or at least nine electrodes arranged in a rectangular array directly in front of the target region.

One aspect provides a method of generating an ECG. The method includes providing an electrode patch comprising a plurality of unipolar precordial electrodes, positioning the electrode array patch in contact with a skin surface of a subject at a position corresponding with an expected location for a myocardial defect, receiving ECG signals from the electrodes, and processing the ECG signals received to detect fractionated conduction delays associated with a myocardial defect of a subject. In one embodiment, positioning comprises arranging the patch in front of an RVOT of the subject, wherein a perimeter of the patch falls interior to a projected perimeter of the RVOT region. A projected perimeter refers to an imaginary perimeter congruent to a front view perimeter of an internal object that is projected forward to a surface such as the skin surface. Positioning may comprise arranging the patch in front of an RVOT of the subject, wherein all of the electrodes are arranged interior to a projected perimeter of the RVOT region. In some embodiments, the fractionated conduction delays comprise one or more of: epsilon waves, late potentials, and coved ST elevation. In other embodiments, the method comprises connecting the plurality of unipolar precordial electrodes and any other electrodes to leads of a standard ECG, Holter ECG, or SAECG system.

One aspect provides a method of generating an ECG, comprising: (a) arranging at least four or at least six unipolar precordial electrodes on a subject's chest in front of a particular area of interest, (b) arranging additional electrodes at other locations of the subject, (c) connecting the electrodes to leads of an ECG machine, (d) receiving signals from the electrodes, (e) processing the received signals, and (f) detecting fractionated conduction delays in the received signals. The method may further comprise: (g) rearranging the at least four unipolar electrodes on a subject's chest in front of another particular area of interest, and (h) repeating steps

(b) - (f).

In one aspect, a lead-array comprises at least three panel options capable of capturing localized late potentials from the corresponding region of right ventricular outflow tract (RVOT), inflow tract (RVIT) and left ventricle (LV) respectively (Figs. 4-5). Some ECG electrode arrangements described herein are expected to be far more sensitive than the conventional SAECG systems for detecting fractionated conduction delays such as regional LPs resulting from diseased myocardium. In one aspect, methods and systems increase the sensitivity of detecting LPs by 50-75% in patients with AMI, ARVD, Brugada syndrome and other sudden death related syndromes.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings illustrate certain embodiments discussed below and are a part of the specification. FIG. IA and IB illustrate a low resolution, ten-electrode, twelve-lead ECG arrangement.

FIG. 1C is a top view or horizontal plane which is perpendicular to the frontal plane illustrated in FIGS. IA and IB.

FIG. 2A represents a heart beat recorded on an ECG and illustrates P-QRS-T waves.

FIG. 2B is a diagram illustrating various parts of the human heart.

FIG. 3 illustrates a standard SAECG system utilizing seven bipolar, orthogonal electrodes.

6 REPLACEMENT SHEET FIG. 4 illustrates an electrode array configuration according to one embodiment of the present invention.

FIG. 5 illustrates an electrode array configuration according to two more embodiments of the present invention. FIGS 6A-6B illustrate various arrangements of electrode arrays in relation to a target region of interest according to some aspects of the present invention.

Throughout the drawings, identical reference characters and descriptions indicate similar, but not necessarily identical elements.

DETAILED DESCRIPTION

Illustrative embodiments and aspects of the invention are described below. It will of course be appreciated that in the development of any such actual embodiment, numerous implementation-specific decisions must be made to achieve the developers' specific goals, such as compliance with system-related and business- related constraints, that will vary from one implementation to another. Moreover, it will be appreciated that such a development effort might be complex and time- consuming, but would nevertheless be a routine undertaking for those of ordinary skill in the art having the benefit of this disclosure.

Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Numeric ranges recited herein are inclusive of the numbers defining the range and include and are supportive of each integer within the defined range. Unless otherwise noted, the terms "a" or "an" are to be construed as meaning "at least one of." The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. All documents, or portions of documents, cited in this application, including but not limited to patents, patent applications, articles, books, and treatises, are hereby expressly incorporated by reference in their entirety for any purpose. One skilled in the art will recognize many methods and materials similar or equivalent to those described herein, which could be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described. For purposes of the present invention, the following terms are defined as set forth below. As used throughout the specification and claims, the term "array" means a two-dimensional arrangement of elements defining an area with a perimeter, an "array" is not substantially linear or arranged in a string-like manner. A "rectangular array" is an ordered arrangement of elements in rows and columns, as in a matrix.

The term "contiguous," as used in reference to the arrangement of precordial electrodes relative to one another, means a plurality of electrodes that share one boundary.

"Circumscribe" means to draw a line around or enclose, not necessarily in any particular pattern.

An "electrode" is an element adapted to contact the skin of a subject and conduct the electrical potential changes in the heart. A standard ECG electrode may have a core (d=10 mm) comprising of a metal conductor and a silver-silver chloride filled with electrical gel. "Epsilon waves" refer to the parietal fractionated conduction delay recorded from standard low resolution ECG, manifested as low-amplitude and low-frequency deflections, appearing in the terminal QRS complex and/or on the early ST segment. In ARVD, epsilon waves are more prevalent in the RVOT region.

The words "including" and "having," as used in the specification, including the claims, have the same meaning as the word "comprising."

The term "late potential," specifically as used in reference to ventricular ECG signals, means a signal characterized by the following diagnostic criteria: QRSD: Filtered QRS duration > 114 msec

RMS40: Root mean square voltage of the last 40 msec of the QRS complex < 20 μV

LAS40: The duration of the low amplitude signals that are < 40μV of the terminal

QRS complex (LAS40) > 38 msec.

The term "lead" refers to an element that connects to an electrode. A "unipolar precordial lead" refers to an ECG lead that records electric potential changes of the heart in a cross sectional plane. In other words, a unipolar precordial lead records the electrical variations that occur directly under or behind the associated electrode. Unipolar precordial leads have a single positive recording electrode and may utilize a combination of other electrodes to serve as a composite negative electrode.

The term "signal averaged ECG" or SAECG means 135 displays of signal- averaged ECG information for normal, biased, and difference signals. Typically, in the application of signal-averaged ECG 135, of primary importance to the medical professional is the flat area immediately following the QRS complex, ST segment 133. ST Segment 133 is targeted because of its lack of signal in the ECG of a normal heart. This lack of signal allows the recognition of the presence of very small-amplitude signals that can occur in people with conduction problems indicative of a susceptibility to arrhythmia or other cardiac tissue abnormality. Further, abnormal signals may also exist within the QRS and be masked by the higher-amplitude signal present there.

"Tight" as in a "tight pattern" means a compact arrangement, or something other than a string-like or substantially linear arrangement. "Tight" or "tightness" of sensing elements means that each element is capable of detecting a particular biological defect with a comparable degree of accuracy and precision.

"Ventricular late potentials (VLPs)" or "late potentials (LPs)" refer to parietal fractionated conduction delay recorded from high resolution ECG such as SAECG. VLPs are characterized as low-amplitude, high-frequency deflections appearing in the terminal QRS complex and/or thereafter. In ARVD patients VLPs are most prevalent in the RVOT region.

The ECG is a graphical representation of the electrical potentials generated by the heart. ECG signals are received by electrodes placed on the body surface and recorded by an ECG machine. The arrangement of ECG electrodes has been standardized over the years to facilitate relatively standard reading of the measurements. For example, a standard low resolution, ten-electrode, twelve-lead ECG is arranged as shown in FIG. IA with six electrodes (V1-V6) across the chest and one electrode on each of the patients arms and legs. The right arm electrode is represented by RA, the left arm electrode is represented by LA, the right leg electrode is represented by RL, and the left leg electrode is represented by LL. FIG. IB also shows the general arrangement of FIG. IA with the addition of various angles that may be useful. FIG. 1C illustrates a top view of FIG. IB. The basic elements of each heart beat recorded on the ECG are P-QRS-T waves (FIG. 2A). The P wave reflects the excitation of the two upper chambers of the heart, the right atrium (RA) and left atrium (LA) (FIG. 2B). The QRS complex (FIG. 2A) represents the excitation conducted within the two lower chambers of the heart, the right ventricle (RV) and left ventricle (LV) (FIG. 2B). The T wave (FIG. 2A) reflects the recovery of the heart following excitation. The interval between QRS and T wave is called an ST segment. Specific changes on the ECG in sinus rhythm are indicative of diseased regions that slow conduction of electrical signals. The delayed or fragmented conduction in the myocardium is a prerequisite for reentrant arrhythmias.

As shown in FIG. 2A, an epsilon wave is an unusual ventricular postexcitation wave (referred to as a "late potential" on SAECG) that is considered a diagnostic marker for the diseased region of slow conduction associated with ARVD. An epsilon wave can be recorded in patients with ARVD. The epsilon wave is a low amplitude ventricular post-excitation wave, occurring after the QRS complex and at the beginning of the ST segment. The presence of the epsilon wave is one of the major diagnostic criteria for ARVD/C because it is a sign of delayed or fragmented conduction within the myocardium due to the presence of diseased tissue. The fragmented conduction can lead to reentry tachyarrhythmias. The epsilon wave is often a very localized phenomenon, more evident in right precordial leads V1-V3, or whichever lead is positioned closest to the disease region. Otherwise, it can be easily neglected due to the very low amplitude. The sensitivity of detecting epsilon waves by standard 12-lead ECG is low; epsilon waves are detectable in low resolution ECGs in only 33% of ARVD patients. The standard 12-Lead ECG is a widely used low-resolution instrument that records nine seconds of cardiac data. As shown in FIG. 1A-1B, the standard 12-lead system uses six positive bipolar electrodes placed on the surface of the chest over the heart in order to record electrical activity in the horizontal plane which is perpendicular to the frontal plane (FIG. 1C). A wave of depolarization traveling toward a particular electrode on the chest surface is recorded as a positive deflection in the ECG output. As mentioned above, only occasionally does the standard 12- lead ECG capture the epsilon wave on precordial leads Vl, V2 or V3. However, due to the very low voltage, most late potentials cannot be shown by the standard low resolution ECG.

The continuous ambulatory electrocardiogram (Holter ECG) has been routinely used for detecting cardiac arrhythmias and myocardial ischemia. The incidence of cardiac arrhythmia and myocardial ischemia, as well as the assessment of heart rate variability on Holter ECG obtained continuously over twenty-four hours or longer have been useful for predicting clinical disease outcomes. A high resolution digital 12-lead Holter ECG can also be used for detecting the fractionated ventricular conduction in both ARVD and BrS, especially in detecting the transitory typical BrS ECG patterns in pre-symptomatic patients. The high resolution Holter ECGs are also helpful in differentiating ARVD from patients with idiopathic right ventricular outflow tract tachycardia. In the latter group, the fragmented ventricular conduction is absent. The absence of fractionated conduction is an indication of a benign prognosis. The precordial lead positions, however, are the same as with the standard resting ECG in that they are not the best lead positions for detecting electrical heart abnormalities.

Signal averaged ECG (SAECG) systems are now widely used to obtain high- resolution ECG data in patients with cardiac disease. As shown in FIG. 3, the standard SAECG lead systems utilize seven bipolar, orthogonal electrodes. The seven electrodes comprise Z+/Z- (horizontal), Y+/Y- (vertical), anterior/posterior electrodes (labeled as Vl, V2), and a ground G lead placed in the manner shown. The Z electrodes are positioned at the forth intercostals space in both midaxillary lines, the Y electrodes are positioned on the superior aspect of the manubrium and on the left iliac crest, and the anterior Z (V2) electrode is positioned at the forth intercostals space, with the posterior Z electrode V2 directly posterior on the left side of the vertebral column. SAECG instruments are used to detect low-amplitude, high-frequency, and altered frequency components in the terminal QRS complex (FIG. 2A), referred to as late potentials (LPs). Similar to the epsilon wave (FIG. 2A), LPs result from delayed or fragmented conduction, which set the substrate for development of reentrant ventricular tachycardia. A positive ventricular LP (VLP) result is a strong indication of increased vulnerability to sustained-ventricular tachyarrhythmia and sudden death in patients with cardiac diseases. Due to the remote distance of the body surface electrodes to the disease region of the heart, large scaled studies suggest the sensitivity of detection of VLPs in high risk patients with acute myocardial infarction (AMI) by conventional SAECG is low (AMERICAN JOURNAL OF CARDIOLOGY 69: 13-21, 1992; POL. ARCH. MED. WEWN. 110(6): 1423-9, 2003). The detection rate is especially low in the early stage of ARVD. (AMERICAN JOURNAL OF CARDIOLOGY 83: 1214-9, 1999). For example, in one study, only 50% of high sudden-death risk patients with acute myocardial infarction (AMI), and only 30% of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) had LPs detected by conventional SAECGs. Such low sensitivity often yields a delayed diagnosis/treatment in patients who bear high risk to sudden arrhythmic death, significantly increasing the risk of death.

As mentioned above, the RVOT is the most common affected area in arrhythmogenic right ventricular cardiomyopathies such as ARVD and BrS. Although they differ by genotype and phenotype characteristics, in both conditions patients have an increased susceptibility to sudden arrhythmic death. Recent studies show the prevalence of ARVD is about 1 : 1,000 among the general population. The prevalence of BrS is about 1: 10,000 among the general population.

Unfortunately the early detection of such sudden arrhythmic death related diseases is not satisfactory. ARVD has often advanced to the late stages by the time it is diagnosed. ECG can be used to diagnose ARVD. The presence of epsilon waves in an ECG is considered a major diagnostic criterion, and the presence of ventricular late potentials (VLPs) is a minor criterion.

In both ARVD and BrS, the RVOT is the most frequently affected region. However as mentioned above, using standard ECG lead placement, the chance of detecting epsilon waves and VLPs in ARVD patients is poor, at best. Similarly, with BrS, the typical coved-type STS elevation pattern mostly originates from the RVOT. Referring to FIG. 3, although the precordial Vi electrode, the V₂ electrode and the orthogonal Z leads are relatively closer to the anterior infundibulum of the right ventricle, the chest RVOT corresponding region actually extends from V₁, sternum and V₂ at the second intercostal space level, to the same positions at the third intercostal level. ECG signals, if acquired from electrodes closer to or adjacent the RVOT region, have a better chance of capturing fractionated conduction delays including RVOT originated epsilon waves, VLPs and coved-ST elevations. Detecting epsilon waves, VLPs and coved-ST elevations improves clinical diagnosis of the underlying cardiac diseases.

Therefore, according to principles described herein, placement of electrodes for an ECG are strategically made to facilitate detection of fractionated conduction delays. Referring to FIG. 4, there is an electrode array such as an electrode array patch 100 according to one embodiment. The electrode array patch 100 of FIG. 4 is a condensed ECG electrode-array designed specifically to detect the fractionated conduction delay that occurs in RVOT diseases such as ARVD and BrS. The electrode array patch 100 includes an adhesive backing for convenient attachment to a subject.

According to one embodiment, the electrode array patch 100 comprises a plurality of electrodes such as unipolar precordial electrodes 102 arranged in a two dimensional array or matrix. In one embodiment, the electrode array patch 100 may replace what was a single electrode (Vi) in an SAECG (FIG. 3). The electrode array patch 100 may also be used with any other ECG system, including, but not limited to the standard 12-lead ECG and a 12-lead Holter ECG system.

In one embodiment, there may be two or four unipolar precordial electrodes 102 embedded or attached to the electrode array patch 100. For example, the unipolar precordial electrodes 102 may be arranged on the electrode array patch 100 in two rows and two columns, forming a 2x2 square array. For the electrode patch, the core (10 mm) to core distance 102 may be approximately 20-30 mm). Therefore, adjacent unipolar precordial electrodes in the same row or column are approximately 20-30 mm apart, and diagonally adjacent electrodes are approximately 28-42 mm apart (28 for 20-mm spacing, 42 for 30 mm spacing). In one embodiment, there may be six unipolar precordial electrodes 102 embedded or attached to the electrode array patch 100. For example, the unipolar precordial electrodes 102 may be arranged on the electrode array patch 100 in two rows and three columns, forming a 2x3 rectangular array. In a 2x3 rectangular array pattern, the maximum distance between any two electrodes is between about 45 and 67 mm (45 mm for 20-mm spacing, 67 mm for 30-mm spacing).

In one embodiment, there may be at least nine unipolar precordial electrodes 102 embedded or attached to the electrode array patch 100 as shown in FIG. 4. For example, the unipolar precordial electrodes 102 may be arranged on the electrode array patch 100 in three rows and three columns, forming a 3x3 rectangular or square array. In a 3x3 rectangular array pattern, the maximum distance between any two electrodes is between about 56 and 85 mm (56 mm for 20-mm spacing, 85 mm for 30-mm spacing). Other arrayed arrangements of the unipolar precordial electrodes 102 may also be used. Nevertheless, in some embodiments, the arrangement of the unipolar precordial electrodes 102 and/or the size of the electrode array patch 100 are such that a sufficient number of electrodes fits inside or falls interior to a target region such as a projected perimeter of the RVOT region 104. Similarly, the arrangement of the unipolar precordial electrodes 102 and/or the size of the electrode array patch 100 may be such that the electrodes fit inside or falls interior to a projected perimeter of an RVIT region or a left ventricular wall region. The unipolar precordial electrodes 102 and/or the electrode array patch 100 may be arranged directly in front of the RVOT in one embodiment. Other embodiments may include placing the unipolar precordial electrodes 102 and/or the electrode array patch 100 directly in front of the RVIT or left ventricle wall as shown in FIG. 5. In some embodiments, although the unipolar precordial electrodes 102 do not lie within the projected perimeter of the RVOT, RVIT, or left ventricle wall area, they are all near or adjust to the projected perimeter. In some embodiments, the unipolar precordial electrodes 102 are arranged together tightly or on a patch that is approximately the same size (in perimeter) as a human heart.

In the embodiment shown in FIG. 4, the unipolar precordial electrodes 102 are positioned adjacent to each other horizontally and vertically. Each unipolar precordial electrode 102 may labeled in order: 1-3 (top row), 4-6 (middle row), 7-9 (bottom row), etc. In one embodiment, the unipolar precordial electrodes 102 comprise a core having a diameter of approximately 10 mm, and each comprises a metal conductor such as silver-silver chloride filled with electrical gel. Around a perimeter each unipolar precordial electrode 102 may be a ring (10-15 mm wide) constructed of sticky tape or other material that tends to seal to the skin of a subject to assure electrode contact with the skin and electrically isolate each electrode to prevent short circuiting.

According to one embodiment, placement of the electrode array patch 100 is facilitated by a diagram printed on the reverse side of the patch. In one embodiment, (for example a 6-electrode patch), the #2 electrode (e.g. the middle electrode of the top row) is placed on the center of the sternum at the second intercostal space level, and the rest of the electrode array patch 100 will fall into correct placement. The electrode array patch 100 may be transparent to facilitate monitored for unipolar precordial electrode-skin contact and unipolar precordial electrode positioning.

According to some embodiments, the electrode array patch 100 may comprise different sizes. For example, one electrode array patch 100 having six electrodes may comprise a rectangle approximately 75 x 115 mm. Another electrode array patch 100 having six electrodes may comprise a rectangle approximately 85 x 128 mm. Another electrode array patch 100 having six electrodes may comprise a rectangle approximately 100 x 150 mm. Accordingly, the electrode array patch 100 may accommodate a variety of body types. Moreover, the electrode array patch 100 may be designed so that it can separate between rows and between columns if necessary in order to achieve the best fit. The electrode array patch 100 may comprise any polygonal or circular (including elliptical) shape, including, but not limited to: triangles, squares, rectangles, pentagons, hexagons, heptagons, octagons, nonagons, and decagons. In one embodiment, the electrode density of the array patch 100 is at least six electrodes per 150 cm (100 x 150 mm). In one embodiment, the electrode density is at least six electrodes per 108.8 cm² (85 x 128 mm). In one embodiment, the electrode density is at least six electrodes per 86.25 cm² (75 x 115 mm). However, any other patch size and any number of electrodes may also be used.

In one embodiment, the electrode array patch 100 is arranged with the electrodes 102 adjacent to an target area of interest such as the RVOT region 104 as shown in FIG. 6A. In one embodiment, the electrode array patch 100 is arranged with all of the electrodes 102 covering or in front of a target region such as the RVOT region 104 as shown in FIG. 6B. In the arrangement of FIG. 6B, the electrode array and the electrode array patch 100 circumscribe the RVOT region 104. In one embodiment, the electrode array patch 100 is arranged with at least a portion of the array of electrodes 102 positioned over or covering a target area such as the RVOT region 104 as shown in FIG. 6C.

According to one embodiment utilizing a standard ECG or 12-lead Holter ECG system, the electrode array patch 100 may have six unipolar precordial electrodes 102 (numbered 1-6), with each unipolar precordial electrode connected to an associated precordial lead (e.g. V₁-Ve in a standard ECG or 12-lead Holter ECG system). In so doing, the ECG signals from the RVOT 104 region are recorded from standard unipolar ECG leads. Similarly, with an SAECG system, the electrode array patch 100 may have six unipolar precordial electrodes 102 connected to the six unipolar leads to enable data acquisition. Although possibly less convenient, it will be understood by those of ordinary skill in the art having the benefit of this disclosure that the unipolar precordial electrodes 102 may be separate, and not attached to the electrode array patch 100 in some embodiments. The electrode array patch 100 (or an arrangement of individual electrodes placed manually) with six unipolar precordial electrodes 102 can be used in with standard ECG and 12-lead Holter ECG systems with no alterations to the ECG devices. However, it may be necessary to add a unipolar ECG panel to SAECG systems to use the electrode array patch 100. This can be easily done by one of ordinary skill in the art having the benefit of this disclosure. Moreover, standard ECG, 12-lead Holter ECG, SAECG systems and any other ECG system may be made to accommodate any number of electrodes in an array or array patch 100. With the use of many unipolar precordial electrodes 102 directly in front of the RVOT, it is believed that the ECG signals acquired from the RVOT region will greatly increase the sensitivity of detecting fractionated conduction delays such as late potentials in patients with in ARVD and Brugada syndrome.

In one embodiment, a twelve-lead array patch (3 x 4) of electrodes is arranged in three rows and four columns. The placement of the third electrode of the third row (or the 3^rd lead on 3rd column) may be removable with a match marker to the main the patch 100 and may be placed to the V₂ position, (left side of the sternum at the forth intercostal space). The rest of the electrodes fall into the place once the patch is matched with V₂ by the marker.

For patients with VTs originating from the RVIT and with negative LP results in RVOT region, the electrode array patch 100 may be placed in front of the RVIT region as shown in FIG. 5. The corresponding chest leads are V4R and V5R. In such an application, the first lead on the second row (second lead of first column) may be detachable with a match marker to the electrode array patch 100, and is positioned in V5R. Moreover, for patients with acute myocardial infarction (AMI), if the infarction is located in the left ventricular wall, the third lead on the third row can be placed on V5 position (FIG. 5) in front of the left ventricular wall, with the rest of the electrode array patch 100 falling into place. This will provide a better window to detect LPs in AMI patients if a negative result is obtained by other electrode arrangements.

The methods and systems described herein are simple to implement in clinical applications. In addition, the methods and systems described will significantly increase the sensitivity of detecting late potentials and other fractionated conduction delays in patients at high risk for sudden arrhythmic death related diseases, especially in arhythmogenic right ventricular dysplasure/cardiomyopathy (ARVD/C) and Brugada syndrome. The methods and systems may also be useful in detecting LPs in the early or concealed stages of the disease. The preceding description has been presented only to illustrate and describe certain aspects, embodiments, and examples of the principles claimed below. It is not intended to be exhaustive or to limit the described principles to any precise form disclosed. Many modifications and variations are possible in light of the above teaching. Such modifications are contemplated by the inventor and within the scope of the claims. The scope of the principles described is defined by the following claims. It will be understood that the figures and accompanying text are exemplary in nature, and not limiting.

Claims

CLAIMS What is claimed is:

1. A portable ECG electrode array adapted to be connected to the skin surface of a subject, comprising: a plurality of unipolar precordial electrodes arranged in a fixed two- dimensional array.

2. A portable ECG electrode array according to claim 1, wherein the plurality of unipolar precordial electrodes is configured to detect fractionated conduction delay.

3. A portable ECG electrode array according to claim 1, wherein the plurality of unipolar precordial electrodes is sufficient in number and size to detect epsilon waves, late potentials, and coved ST elevation associated with a myocardial defect of a subj ect.

4. A portable ECG electrode array according to claim 1, wherein the array comprises a rectangular array of rows and columns of the unipolar precordial electrodes, wherein a number of rows and a number of columns is within one unit of one another.

5. A portable ECG electrode array according to claim 1, wherein the array comprises a square array of rows and columns of the unipolar precordial electrodes, wherein a number of rows and a number of columns is equal.

6. A portable ECG electrode array according to claim 1, wherein the array comprises a rectangular array of rows and columns of the unipolar precordial electrodes arranged in a tight pattern approximately a size of a human heart.

7. A portable ECG electrode array according to claim 1, wherein the array comprises an efficiently compact arrangement of the unipolar precordial electrodes.

8. A portable ECG electrode array according to claim 1, wherein the array comprises fewer than thirty-two unipolar precordial electrodes.

9. A portable ECG electrode array according to claim 1, wherein the array comprises nine or more unipolar precordial electrodes arranged in an array comprising at least three aligned columns and three aligned rows.

10. A portable ECG electrode array according to claim 1, wherein the array comprises six or more unipolar precordial electrodes arranged in an array comprising at least three columns and two rows.

11. A portable ECG electrode array according to claim 1, wherein the array comprises four unipolar precordial electrodes arranged in an array comprising two columns and two rows.

12. A portable ECG electrode array according to claim 1, wherein the unipolar precordial electrodes are positioned substantially equidistant from each other.

13. A portable ECG electrode array according to claim 1 , wherein the distance between a core of each electrode of the array ranges between about 20 and 30 mm.

14. A portable ECG electrode array according to claim 1, wherein at least a portion of the array is positioned directly in front of an expected myocardial defect area of the subject.

15. A portable ECG electrode array according to claim 1, wherein at least a portion of the array is positioned in front of the right ventricular outflow tract (RVOT) of the subject.

16. A portable ECG electrode array according to claim 1, wherein all of the electrodes of the array are positioned over the right ventricular outflow tract (RVOT) of the subject.

17. A portable ECG electrode array according to claim 1, wherein the array circumscribes the right ventricular outflow tract (RVOT) of the subject.

18. A portable ECG electrode array according to claim 1, wherein the array is positioned adjacent to the right ventricular outflow tract (RVOT) of the subject.

19. A portable ECG electrode array according to claim 1, wherein at least a portion of the electrodes are positioned over a right ventricular inflow tract (RVIT) of the subject.

20. A portable ECG electrode array according to claim 1, wherein all of the electrodes are positioned in front of the left ventricular wall of the subject.

21. A portable ECG electrode array according to claim 1 , wherein a density of the unipolar precordial electrodes comprises at least six electrodes per 150 cm².

22. A portable ECG electrode array according to claim 1, wherein a density of the unipolar precordial electrodes comprises at least six electrodes per 108.8 cm².

23. A portable ECG electrode array according to claim 1, wherein a density of the unipolar precordial electrodes comprises at least six electrodes per

86.25 cm²

24. A portable ECG electrode array according to claim 1, wherein the fixed two-dimensional array comprises a patch, and further comprising adhesive to attach the patch to a subject.

25. A portable ECG electrode array according to claim 1, wherein the fixed two-dimensional array comprises the plurality of unipolar precordial electrodes disposed in an adhesive patch and configured to detect fractionated conduction delay originating from an RVOT region of a subject heart.

26. A portable ECG electrode array according to claim 25, wherein the adhesive patch comprises a geometric shape and a density of the unipolar precordial electrodes disposed in the adhesive patch comprises at least six electrodes per 150 cm

27. A portable ECG electrode array according to claim 25, wherein the adhesive patch comprises a geometric shape and a density of the unipolar precordial electrodes disposed in the adhesive patch comprises at least six electrodes per 108.8 cm

28. A portable ECG electrode array according to claim 25, wherein the adhesive patch comprises a geometric shape and a density of the unipolar precordial electrodes disposed in the adhesive patch comprises at least six electrodes per 86.25 cm

29. A portable ECG electrode array according to claim 25, wherein the adhesive patch comprises a geometric shape selected from the group consisting of: circle, rectangle, square, triangle, pentagon, hexagon, heptagon, octagon, nonagon, and decagon.

30. A portable ECG electrode array according to claim 1 wherein the plurality of unipolar precordial electrodes comprises at least six electrodes and a maximum distance between any two electrodes is about 67 mm.

31. A portable ECG electrode array according to claim 1 wherein the plurality of unipolar precordial electrodes comprises at least nine electrodes and a maximum distance between any two electrodes is about 85 mm.

32. A portable ECG electrode array according to claim 1, wherein the fixed two-dimensional array comprises an array patch, the array patch comprising: the plurality of unipolar precordial electrodes configured to be attached to the skin surface of a subject on an adhesive patch and arranged in a rectangular array.

33. A portable ECG electrode array according to claim 32, wherein the adhesive patch is substantially the same size as a human heart.

34. A portable ECG electrode array according to claim 32, wherein the adhesive patch is sized to substantially cover the RVOT region of a human heart.

35. A portable ECG electrode array according to claim 32, wherein the adhesive patch is sized to cover an RVOT human heart region, from IC2-Vi, sternum, and IC2-V₂ at a second intercostal space level, to corresponding positions at a third intercostal level IC3-V1 and IC3-V2 respectively.

36. A portable ECG electrode array according to claim 32 wherein the plurality of unipolar precordial electrodes comprises at least six electrodes and a maximum distance between any two electrodes is about 67 mm.

37. A portable ECG electrode array according to claim 32 wherein the plurality of unipolar precordial electrodes comprises at least nine electrodes and a maximum distance between any two electrodes is about 85 mm.

38. A portable ECG electrode array according to claim 32 wherein the adhesive patch is transparent.

39. A portable ECG electrode array patch according to claim 32 wherein the rectangular array comprises six ECG electrodes arranged in three columns and two rows, wherein each electrode is connected to an associated precordial lead of a standard ECG machine.

40. A portable ECG electrode array according to claim 32 wherein the rectangular array comprises six ECG electrodes arranged in three columns and two rows, wherein each electrode is connected to an associated precordial lead of a twelve-lead Holter ECG system.

41. A portable ECG electrode array according to claim 32 wherein the rectangular array comprises six ECG electrodes arranged in three columns and two rows, wherein each electrode is connected to an associated unipolar lead of an SAECG system.

42. A portable ECG electrode array according to claim 32, wherein at least a portion of the array patch is positioned over the myocardial defect of the subject.

43. A portable ECG electrode array according to claim 32, wherein at least a portion of the array patch is positioned over the right ventricular outflow tract (RVOT) of the subject

44. A portable ECG electrode array according to claim 32, wherein the electrodes are positioned over the right ventricular inflow tract (RVIT) of the subject.

45. An ECG electrode array patch according to claim 32, wherein the electrodes are positioned over the left ventricular wall of a subject.

46. A portable ECG electrode array according to claim 32 wherein each of the plurality of unipolar precordial electrodes is connected to an associated precordial lead of a twelve-lead Holter ECG system.

47. A portable ECG electrode array according to claim 32 wherein each of the plurality of unipolar precordial electrodes is connected to an associated unipolar lead of an SAECG system.

48. An apparatus, comprising: an ECG system, the ECG system comprising: a plurality of electrodes arranged contiguously in a fixed coplanar two-dimensional array in sufficient number and size to detect low voltage ventricular late potentials associated with a myocardial defect of a subject; an ECG recorder comprising leads connected to the plurality of electrodes.

49. An apparatus according to claim 48, wherein the electrodes comprise unipolar precordial electrodes.

50. An apparatus according to claim 49, wherein the plurality of unipolar precordial electrodes is paired with a posterior electrode arranged opposite of the plurality of unipolar precordial leads; and further comprising: a pair of horizontally spaced electrodes for arrangement at opposite sides of the subject; a pair of vertically spaced electrodes for arrangement above and below a heart of the subject; a ground electrode.

51. A method of generating an ECG, comprising: arranging at least four electrodes on a subject's chest in front of a target region contiguously in a fixed two-dimensional array; arranging additional electrodes at other locations of the subject; connecting the electrodes to leads of an ECG machine; receiving signals from the electrodes; processing the received signals; detecting fractionated conduction delays in the received signals.

52. A method according to claim 51 wherein the at least two electrodes comprise unipolar precordial electrodes.

53. A method according to claim 51, wherein the detecting fractionated conduction delays comprises detecting epsilon waves.

54. A method according to claim 51, wherein the detecting fractionated conduction delays comprises detecting late potentials.

55. A method according to claim 51, wherein the detecting fractionated conduction delays comprises detecting coved ST elevation.

56. A method according to claim 51 wherein the target region comprises an RVOT region.

57. A method according to claim 51, wherein the arranging at least four electrodes comprises placing a patch comprising at least six electrodes arranged in a rectangular array substantially in front of the target region.

58. A method according to claim 51, wherein the arranging at least fourt electrodes comprises placing a patch comprising at least nine electrodes arranged in a rectangular array substantially in front of the target region.

59. A method of generating an ECG, comprising providing an electrode patch comprising a plurality of unipolar precordial electrodes; positioning the electrode array patch in contact with a skin surface of a subject at a position corresponding with an expected location for a myocardial defect; receiving ECG signals from the electrodes; processing the ECG signals received to detect fractionated conduction delays associated with a myocardial defect of a subject.

60. A method according to claim 59, wherein positioning comprises arranging the patch in front of an RVOT of the subject, wherein a perimeter of the patch falls interior to a projected perimeter of the RVOT region.

61. A method according to claim 59, wherein positioning comprises arranging the patch in front of an RVOT of the subject, wherein all of the electrodes are arranged interior to a projected perimeter of the RVOT region.

62. A method according to claim 59, wherein the fractionated conduction delays comprise one of: epsilon waves, late potentials, and coved ST elevation.

63. A method according to claim 59, wherein the method comprises connecting the plurality of unipolar precordial electrodes and any other electrodes to leads of a standard ECG, Holter ECG, or SAECG system.

64. A method of generating an ECG, comprising:

(a) arranging at least four unipolar precordial electrodes on a subject's chest in front of a particular area of interest;

(b) arranging additional electrodes at other locations of the subject; (c) connecting the electrodes to leads of an ECG machine;

(d) receiving signals from the electrodes;

(e) processing the received signals;

(f) detecting fractionated conduction delays in the received signals.

65. A method according to claim 64, further comprising:

(g) rearranging the at least four unipolar electrodes on a subject's chest in front of another particular area of interest;

(h) repeating steps (b) - (f).

66. A method according to claim 64 wherein the arranging at least four unipolar precordial electrodes comprises arranging at least six unipolar precordial electrodes on a subject's chest in front of a particular area of interest.

67. A method of generating an ECG, comprising:

(a) arranging at least four precordial electrodes on a subject's chest in front of a particular area of interest;

(b) arranging additional electrodes at other locations of the subject;

(c) connecting the electrodes to leads of an ECG machine; (d) receiving signals from the electrodes;

(e) processing the received signals;

(f) detecting fractionated conduction delays in the received signals.

68. A portable ECG electrode array adapted to be connected to the skin surface of a subject, comprising: a plurality of electrodes arranged in a fixed two-dimensional array.