U.S. patent application number 10/078355 was filed with the patent office on 2002-09-26 for system for analysis of biological voltage signals.
Invention is credited to Guerrero, Juan C., Guerrero, Juan R..
Application Number | 20020138013 10/078355 |
Document ID | / |
Family ID | 26800137 |
Filed Date | 2002-09-26 |
United States Patent
Application |
20020138013 |
Kind Code |
A1 |
Guerrero, Juan R. ; et
al. |
September 26, 2002 |
System for analysis of biological voltage signals
Abstract
Method of analyzing biological signals, including obtaining a
magnetic recording media having an analog biological signal
recorded thereon, using digital processing software to digitize the
biological signal, displaying the digitized biological signal in
analog form on a display, and visually analyzing the biological
signal on the display. The biological signal may be an
electrocardiogram. Preferably, independent channel enhancement of
the dynamic range of the analog biological signal is performed
prior to digitizing The displayed biological signal is preferably
presented in time compressed form. Digitizing is performed by
sampling the biological signal at at least approximately 44,100 Hz
per second per channel and quantization of at least 16-bits per
sample per channel. The digital processing software is preferably
digital audio processing software.
Inventors: |
Guerrero, Juan R.; (Durham,
NC) ; Guerrero, Juan C.; (Durham, NC) |
Correspondence
Address: |
NIXON & VANDERHYE P.C.
8th Floor
1100 North Glebe Rd.
Arlington
VA
22201-4714
US
|
Family ID: |
26800137 |
Appl. No.: |
10/078355 |
Filed: |
February 21, 2002 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10078355 |
Feb 21, 2002 |
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09405233 |
Sep 24, 1999 |
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6370423 |
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60103154 |
Oct 5, 1998 |
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Current U.S.
Class: |
600/509 |
Current CPC
Class: |
G16H 50/30 20180101;
A61B 7/003 20130101; A61B 5/7232 20130101; A61B 5/369 20210101;
A61B 5/7275 20130101; G16H 30/40 20180101; A61B 5/389 20210101;
A61B 5/7257 20130101; A61B 5/339 20210101; A61B 5/35 20210101; A61B
5/7445 20130101; G16H 50/20 20180101; A61B 7/04 20130101 |
Class at
Publication: |
600/509 |
International
Class: |
A61B 005/04 |
Claims
What is claimed is:
1. Method of analyzing biological signals, comprising obtaining a
magnetic recording media having an analog biological signal
recorded thereon, using digital processing software to digitize
said biological signal, displaying said processed biological signal
in analog form on a display, and visually analyzing said biological
signal on said display.
2. Method of claim 1, wherein said biological signal is an
electrocardiogram.
3. Method of claim 1, further including performing independent
channel enhancement of the dynamic range of said analog biological
signal prior to said digitizing.
4. Method of claim 1, wherein displaying includes displaying said
biological signal in time compressed form.
5. Method of claim 1, wherein visually analyzing includes
attempting to match patterns in said biological signal with a given
library of patterns.
6. Method of claim 1, wherein electronic independent optimization
of the dynamic range in each channel is done prior to said
digitizing.
7. Method of claim 1, wherein said digitizing is performed by
sampling said biological signal at at least approximately 44,100 Hz
per second per channel.
8. Method of claim 7, wherein said digitizing is performed using
quantization of at least 16-bits per sample per channel.
9. Method of claim 1, wherein said digital processing software is
digital audio processing software.
10. Method of claim 1, further including the step of using time
intervals in the biological signal to asses internal functional
harmony of the biological signal.
11. Method of claim 1, wherein digitizing includes using computer
sound cards to digitize the biological signal.
12. Method of claim 1, wherein visually analyzing said displayed
signal includes looking for abnormalities from the group consisting
of: myocardial ischemia, arrhythmia, repolarization, depolarization
heterogeneity, and pacemaker malfunction.
13. Method of claim 1, wherein said displaying includes magnifying
said displayed biological signal in a Y axis to enable at least
microsecond levels of said biological signal to be viewed.
14. Method of claim 1, wherein said displaying includes magnifying
said displayed biological signal in an X axis to enable at least
microvolt levels of said biological signal to be viewed.
15. Method of claim 1, further including using said method for mass
screening of the human population for abnormalities.
16. Method of claim 1, wherein said magnetic recording media is a
cassette tape and said digitization includes using a slow playback
speed for said cassette tape.
17. Method of claim 16, wherein said slow playback speed is
selected to be approximately 40 mm per second.
18. Method of claim 8, wherein said magnetic recording media is a
cassette tape and said digitization includes using a slow playback
speed for said cassette tape.
19. Method of claim 1, wherein said biological signal is an
electroencephalogram.
20. Method of claim 1, wherein said biological signal is a
myogram.
21. Method of claim 1, wherein said biological signal is a
phonocardiogram.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application hereby claims priority on U.S. Provisional
Application No. 60/103,154 filed Oct. 5, 1998, the disclosure of
which is hereby incorporated by reference herein in its
entirety.
FIELD OF THE INVENTION
[0002] The instant invention relates to improved methods and
systems for analysis of dynamic electrocardiograms and other
similar waves of biological origin with the purpose of facilitating
improved diagnosis of pathological states in human and veterinary
medicine. More particularly, the instant invention advantageously
uses advances in sound wave technology to improve the recovery,
preservation, enhancement and cost effective analysis of biological
signals to aid research as well as medical and veterinary
diagnosis.
BACKGROUND OF THE INVENTION
[0003] Coronary heart disease is the main cause of death in many
countries. About 50% of those affected do not reach the hospital
due to poor recognition of the disease before a cataclysmic, often
terminal event has occurred. The present invention facilitates
improved recognition of myocardial ischemia in and out of the
hospital by lay people with minimum training. Once the nature of
the event is recognized, prompt treatment can then be obtained with
a net effect in the decrease of morbidity and mortality and thereby
providing substantial gains in life span and in quality of
life.
[0004] Heretofore, visual analysis of the ambulatory
electrocardiogram, in its original analog format, has been and
remains unsurpassed and it is superior to any and all current
computerized forms of analysis. Visual analysis is a very time
consuming (hence costly) process, which required an operator with
intimate knowledge of electrocardiography and cardiology. For this
reason the use of visual analysis has been limited to academic
research and it has not been possible to extend its benefit to
patient care in the community. The instant invention overcomes this
problem and enables identification of the abnormal patterns by any
person with normal intelligence with a minimum (few hours) amount
of training in the recognition of the discrete visual patterns
which are repetitive between and within patients.
[0005] The instant invention, referred to herein as the
Computerized Visual Analysis Technique or "CVAT", generally relates
to the use of state-of-the-art electronics, computer hardware and
software and forward looking signal analysis principles of
technology for the evaluation of biological signals obtained from
isolated cells, tissues, human and animal species to aid research
and diagnosis of medical and veterinary disease states. CVAT can be
used to process biologic signals such as, but not limited to: 1)
the electrocardiogram in all it's forms, and in particular, the
continues electrocardiographic signal such as that obtained with
the Holter technique or during on-line, real time monitoring of a
patient; 2) the electroencephalogram; 3) the myogram; 4) the
phonocardiogram; and 5) Respiratory sound waves including their
correlation with the electrocardiogram and encephalogram to
diagnose sleep disorders in the hospital and in out of hospital
settings.
[0006] CVAT remedies major limitations of the current Holter
analysis paradigm which is useful only to detect gross arrhythmia
on the 24-hr electrocardiogram (ECG). Current computerized analysis
of the ambulatory ECG is done without due regards for protection of
the integrity, fidelity, resolution or dynamic range of the analog
signal recorded. The current methods are unable to reliably detect
ambulatory ischemia or risk for potentially lethal arrhythmia. Such
risks are not detectable in a cost-effective manner with prior art
techniques. These shortcomings of the prior art have a significant
impact on cardiovascular morbidity and mortality. CVAT remedies the
failure of the current methodology by making full use of the
valuable information encoded in the ambulatory electrocardiogram.
By failing to disclose evidence of risks for catastrophic events,
current Holter analysis lulls clinicians into the falsehood of
absence of evidence misrepresented as evidence of absence of
potentially lethal risks. Consecutive obsolete methodologic steps
in current Holter analysis severely diminish the quantity and
degrade the quality of the signal encoded in original Holter
recording media.
[0007] Mass screening for patients silently at risk for potentially
lethal cardiovascular events could save hundreds of thousands lives
in the United States alone. Well done ambulatory ECG monitoring is
the only method able to detect transient myocardial ischemia and
spontaneously occurring electrical alternans. More than half of the
myocardial infarcts and sudden cardiac deaths happen without any
prior history of cardiac disease. The instant inventor has
determined that these occult and lethal risks can be detected and
lives saved if Holter analysis is done with all the resources made
available by the fast advances constantly made in signal analysis
and computer technology.
[0008] As many as 80 to 100% of the myocardial ischemic episodes in
a patient can be asymptomatic or have uncharacteristic
manifestations known as "anginal equivalents" by cardiologists but
frequently undetected by non-cardiologists. Silent and or
uncharacteristic ischemic events are common especially in females,
diabetics, hypertensives, smokers, hypercholesterolemics, etc.
Endothelial cell dysfunction and occult coronary heart disease are
frequently hidden pathophysiologic causes of catastrophic or lethal
cardiac events.
[0009] Silent ischemia, especially that which is not induced by
physical stress, can be detected only by ambulatory ECG. However,
today, the only reliable form of Holter analysis is visual scanning
of the magnetic tape itself, not the "over reading" of the expunged
and distorted digital file which misrepresents the original signal.
Visual analysis by an expert electrocardiographer is a very time
consuming method used only by highly motivated experts in research
programs. Due to time and cost involved, visual analysis of the
analog signal cannot be applied to clinical practice or mass
screening of at risk population with known methods. To detect
ischemia, special attention must be paid to microvolt range changes
in the ECG, which are not preserved or duly analyzed by current
Holter algorithms. There is a need in the art to develop an
improved method of Holter analysis that can be made cost effective
by not requiring highly sophisticated operator skills. In
accordance with the invention, preservation of the signal
integrity, dynamic range, fidelity and resolution in the time and
voltage domains are of paramount importance for accurate diagnosis
of electrocardiographic abnormalities. These considerations are
literally of vital importance especially regarding the microvolt
region of the ECG where the ventricular repolarization is
encoded.
[0010] The current computerized methods of Holter analysis use
communications engineering techniques and thoroughly obsolete
computer hardware and software. Communications engineering
paradigms and techniques are best limited to the evaluation of
non-biological signals where reproducibility and repetition of
waves and other phenomena are the norm. Biologic signals, such as
the electrocardiogram, arise from complex biological entities where
individuality, constant variation and irreproducibility are
expected. A major drawback of engineering autocorrelation is that
it is sensitive to waveform changes in the time domain (X-axes) and
poorly sensitive to changes in the voltage domain (Y-axes). In
current Holter analysis, autocorrelation is wrongly applied to a
small sample of degraded biological signal with poor dynamic gain
which magnifies the limitations of autocorrelation to recognize
voltage changes. Non-biological techniques used to analyze
biological data yield, at best, mediocre results, which become poor
when analysis is done using a distorted, minuscule fraction of the
original signal recorded.
[0011] The present invention remedies the deficiency of the current
art by completely turning away from over reliance in engineering
paradigms not applicable to biology and technology and methodology
which has long become obsolete. Rather than using autocorrelational
techniques, CVAT analyzes morphology, visual patterns and internal
harmony in the time intervals. Since it's discovery at the
beginning of the century, electrocardiography remains a highly
visual, pattern and morphology based discipline. Despite
sophisticated efforts (such as neural network or fractal
strategies) to advance computer science, humans still do better
visual pattern recognition than computers. In CVAT, morphologic
patterns are quickly and easily recognized by non sophisticated
technicians. Expansion of abnormal, visually compressed, ECG
patterns lead to precise identification of important, classical
electrocardiographic signs that can not be identified by current
Holter analysis. CVAT evaluates time intervals as reflection of
harmony or disharmony within the recording; comparisons with the
"norm" are done with caution. Current Holter computer analysis
relies on quantification of duration and voltages in a digital file
degraded in quantity and quality to compare these findings to
idealized "normal" values obtained with different and better
equipment.
[0012] There are two basic types of ambulatory ECG recording
systems. The "retrospective" system (commonly known as Holter
recording) analyzes the collected data after completion of the
signal recording phase. The "real-time" system analyzes data as it
is being recorded. Retrospective systems record the ECG on magnetic
tape (usually the cassette type) or flash cards to subsequently
analyze the data. In either system, the recording is done through a
plurality of input leads attached through electrodes to various
points on the patient's chest. To analyze the ECG, real-time
systems generally include a microprocessor in conjunction with the
electronic storage device. Both the real-time and the retrospective
recording systems are designed to interface with a scanner through
a magnetic tape reader or an electronic interface to download the
collected information for analysis, editing, storage, and
reporting.
[0013] To record sound, cassette decks use a magnetic tape speed of
55 mm per second across the recording head. For Holter recording
the tape speed is reduced 50 to 100 times to speeds of 1.1 to 0.55
mm per second. Such drastic speed reduction is necessary to do 24
hours recordings without changing cassettes. Speed fluctuation in
the 10% range is a signal acquisition problem; the best research
efforts have dropped it to 3%, which is still too high for accurate
quantitative ECG analysis. The time-base fluctuation is magnified
when the low-speed recording is played back at very high speeds.
The magnetic tape is orders of magnitude richer in signal quantity
and quality than the very small digital file used for current forms
of analysis. The norm today is to digitize the analog signal by
playing back the cassette tapes at speeds as fast as 480 times real
time; this is the beginning of major degradation of the analog
ECG.
[0014] Cassette tape decks used for Holter processing are
inexpensive, less than precise instruments. High-speed playback
degrades fidelity by limiting frequency response. Inaccuracy and
signal deterioration is also introduced by biasing and/or
misalignment of the tape on the play back head during high-speed
play back. Tape stretching due to repeated stopping and starting of
the tape is another source of signal degradation. CVAT solves these
problems, in part, by using the high quality decks to play back the
tape once, in an uninterrupted manner, at a speed preferably lower
than 37 times real time. The digital signal may, for example, then
be copied from a hard drive and archived in a compact disc.
[0015] Independent channel enhancement of the dynamic range is an
important step introduced by CVAT and not done in the current
Holter art. The signal encoded in each channel of the magnetic tape
is fed into a sound mixer for independent expansion of the dynamic
range prior to digital encoding using the best possible or high
quality sound card. In accordance with the invention, sampling of
the analog signal is preferably done at rates of 44,100 to 96,000
Hz with 16-bits quantization, per sample, per channel. Higher
sampling and quantization rates may also be used. The current
Holter art samples, at best, at 8,000 Hz with 8-bits cards without
preservation of the signal integrity or enhancement of dynamic
range prior to analog to digital conversion.
[0016] Current Holter analysis is entirely dependent upon the
extraction of an unselected fraction of the analog signal encoded
in a 24-hour Holter tape. Current algorithms use elision and
omission of vast amounts of the originally recorded ECG signal to
achieve extreme, unnecessary and deleterious data compression. For
instance, at the June 1999 Drug Information Association meeting,
Mortara et al. announced, as a novel achievement, the launch of 24
hr 12 leads Holter that will be stored in 16 megabytes of a flash
card (over 100,000 heart beats in 1.33 MB per lead per 24 hr).
Obsolete clipping and distortion of the signal housed in novel
media.
[0017] On the surface, the quest for radical compression strategies
("decimating") would seem to be adequate in that it saves memory
and greatly enhances the portability of Holter data. However,
extreme digital compression gravely decreases the integrity,
fidelity, resolution and most importantly the dynamic range of the
stored electrocardiogram or any other signal. Furthermore, in the
current art, Fast Fourier Transformation is used to artfully create
"imaginary points" to replace discarded original data and "smooth"
the now partially fictitious signal. Such creative approach is done
after drastic lossy compression has irretrievably discarded more
than 90% of the original signal with great loss of integrity,
dynamic range, resolution and fidelity. The end product is the
current art's inability to detect ischemia, pacemaker malfunction,
arrythmogenic risk or any condition other than gross ventricular
arrhythmia.
[0018] Gross data clipping and "imaginary" data points only
partially explain the major limitations of today's Holter analysis.
The continuing use of vastly outmoded computer and signal
processing technology impede the use of Dr. Norman Holter's
invention to it's full diagnostic potential to save human lives.
Data compression strategies used in current Holter analysis date
back to the accidental creation of the Y2K problem. Obsolete and
unnecessary compression strategies reduce 24-hours worth of analog
Holter data down to a little more than a single megabyte digital
file. When the algorithms for Holter analysis were created, extreme
limitations in available memory existed. Thus, extreme data
compression was needed. It is not accidental that the 1 megabyte
and fraction file was perfectly portable in a single 3.5" magnetic
floppy disk and suitable for telephonic transmission with now
grossly obsolete modems. The fact that Apple Computers, Inc. has
altogether ceased to issue computers with 3.5" magnetic floppy disk
drives is an indication of how outmoded such a standard for
data-volume has become. Thirty years ago, in the infancy of the
computer industry, when silicon chips were as expensive as they
were limited in their RAM or ROM capacity, data compression was a
necessary evil. The Y2K problem was created by a generation of
computer programmers who, squeezing every last bit of possibly
available data space from the mainframes and PCs of the past,
deemed it frivolous to reserve then-precious RAM or ROM memory for
the two digits `19` in any and all indications of the year. Now
that computer memory is as cheap as it is truly vast in capacity,
data compression is an undesirable tool mainly used by producers of
entertainment and other non-essential computer applications, i.e.
whenever loss of data is deemed acceptable for reasons of
practicality and/or fast transmission over consumer-level internet
connections.
[0019] Like all biologic signals, ECG, as audio data are remarkably
hard to compress effectively. All compression routines are known to
deteriorate dynamic range, signal quantity and quality. For 8-bit
data, a Huffman encoding of the deltas between points has been used
in current Holter analysis but deterioration of the signal is quite
evident. For 16-bit data, companies like Sony and Philips are
spending millions of dollars to develop proprietary schemes that as
yet are not fully successful. If somehow, truly non-lossy audio
compression would become able to compress 350 megabytes (the size
of a CVAT 24 hr ECG file) of data and, even more importantly,
preserve high fidelity, resolution and dynamic range intact within
a single megabyte of memory, such a compression strategy would be
almost a miraculous gift to the computer industry and technology in
general. Although great strides of innovation are now being made in
techniques of data compression, a 350:1 data compression ratio
keeping the integrity of the signal is as yet impossible, nor is it
necessary. The fundamental pitfalls of current Holter algorithms
are the same than those which were silently at work in the creation
of the Y2K bug: automated data compression algorithms which discard
data deemed inessential to the projected application. To be of any
value, pre-compression selection of data to be invisible,
inaudible, illegible, or otherwise useless, is a must. The problem
is that such pre-compression decision regarding ambulatory ECG
signal is not and can not be made without rendering compressed
Holter files useless except for detection of gross arrhythmia.
[0020] The much-hyped MPEG Layer 3 (or `MP3`) strategy of digital
audio compression, for instance, uses a psychoacoustic algorithm to
determine which sonic frequencies in a given audio recording remain
ultimately audible to the ear of a listener. The data corresponding
to all `irrelevant` frequencies are then omitted from the resulting
compressed sound files. Although the algorithm used in MP3
compression is quite advanced, the process still degrades the
quality of the original signal in an invariably noticeable (almost
`trademark`) fashion. Such degradation, however, lies within an
`acceptable` window of loss for the consumer-oriented purposes of
the technology, i.e. exchanging recordings of popular songs over
the Internet. Boasting a powerful 12:1 compression ratio, MP3 is a
fairly new compression strategy. Even newer, `better` strategies
are being invented on almost a quarterly basis, but all of them,
even the latest `fractal` compression strategies, still ultimately
boil down to the same compression paradigm: automation of the a
priori decision to selectively preserve or omit certain types of
data. Detection of microvolt and lower voltage changes in the ECG
is relatively new in the electrophysiology lab and now brought to
ambulatory ECG with the instant CVAT method. It is not yet known
which voltage changes are unimportant and to be disposed with
impunity.
[0021] One overriding fact remains clear: the application of any
inherently omissive data compression strategies to a 24 hr ECG
recording prior to any and all analysis of the totality of the
signal is wrong. The only possible use of such indiscriminately
selected file is detection of conditions expected to be apparent
within the grossly compressed version of the ECG signal. For the
current Holter analysis, that condition was and remains gross
arrhythmic events. For a phenomenon as eponymously elusive as
`silent ischemia`, for instance, such a stark predetermination of
what will and will not be detectable in an electrocardiogram is,
literally, the most fatal omission of all. Detection of silent
ischemia and risk of fatal arrhythmia is done in the microvolt
region of the signal, the area that suffers the most from dynamic
range and signal quality deterioration due to obsolete signal
processing schemes. Current Holter analysis continuing reliance
upon obsolete signal and data handling strategies limits access
only to that portion of ECG data which was thought worth
representing within a single megabyte of computer memory more than
10 years ago. Holter analysis remains a vastly under addressed
technological obsolescence which is an obstacle for detection of
risk for lethal events and in doing so puts lives directly at
risk.
[0022] The numbers speak for themselves: Digital compression of 24
hours of recorded signal down to as low as a single megabyte
unnecessarily omits about 99.6% of the ECG which can be easily
retrieved from the average 24-hour magnetic Holter tape. It is like
attempting to "read" a book while missing 99.6% of the words or
"watch" a film with 99.6% of the celluloid frames omitted.
Diagnosis of potentially life threatening conditions can and should
not be made based on such scanty and non-discriminatingly selected
fraction of the ECG stored in the original recording media. Human
life protection deserves better than that.
[0023] The instant CVAT process for Holter analysis utilizes a
completely different method of "data compression" altogether, one
which does not omit any portion or aspect of the originally
recorded ECG Holter data. Instead of destructive fast play back of
the tape and digital compression of the Holter data, CVAT improves
the dynamic range electronically prior to slowly encoding the
whole, unmodified analog signal using the highest possible sample
rate and quantization. CVAT decodes the digital file into an
optimum analog display which itself can be visually compressed,
magnified at will and processed without suffering any loss, but
rather being enhanced by various different processes which are made
available by CVAT and its related software. In addition, the only
limits containing further development and refinement of the CVAT
process are those temporarily imposed by the ephemeral and upwardly
spiraling limits of computer and signal analysis technology. The
CVAT process remains an infinitely upgradeable, high-quality system
which takes Holter analysis orders of magnitude beyond current
techniques.
[0024] Referring now to FIG. 1, there is shown a exemplary Holter
electrocardiogram. The P wave is the ECG representation of the
atrial depolarization which cause its contraction. PQ is the
segment between the P and the Q; it represents the delay of the
electrical wave of depolarization at the atrioventricular node to
allow the contraction of the atria and fill the ventricles before
the latter depolarize and expel blood into the body. Ta (a
microvolt shift in the PQ not present in this figure) is due to
abnormal atrial repolarization caused by ischemia. The QRS is the
ECG representation of ventricular depolarization which cause
ventricular contraction. The ST segment represents the initial
repolarization of the ventricles. The ascending limb of the T wave
represents epicardial (outer surface of the ventricle)
repolarization which changes into endocardial (inner surface of the
ventricle) and mesocardial repolarization at the apex of the
upright T wave. Ventricular repolarization is complete when the T
wave returns to the isoelectric line. Several different
morphologies of the T wave are associated with non-homogeneous
repolarization, a sign of myocardial cell hypoxygenation and risk
for lethal arrhythmia. TP is the isoelectric segment between the
offset of the T and the onset of the P waves. TP must be considered
as the isoelectric line when Ta is present. The second beat is a
premature depolarization characterized by abnormal QRS and T
morphology as well as greater voltage and duration than the normal
beats.
[0025] Experts in non-ambulatory electrocardiography do visual
analysis of the 12 lead ECG using 10.times. optical magnification
for which special tracings are taken at two or four times the
normal paper speed (i.e. 50 to 100 mm per second paper speed) with
at least twice the electrical gain (i.e. 1 millivolt inscribing a
20 mm deflection). The tracings are done using good quality, well
maintained and well-calibrated stationary electrocardiographs. The
best examples of this art are in research done in Scandinavia.
There is a pressing need to apply similar or better care to the
processing and analysis of the ambulatory electrocardiogram.
[0026] Norman J. Holter Ph.D. created Holter technology using
radio-transmitted electrocardiograms in the 1940's. The method was
used for diagnosis of arrhythmia. The first algorithms for computer
assisted analysis were designed to detect and classify premature or
aberrant beats for the diagnosis of arrhythmia. Attempts to
automate detection of myocardial ischemia started in the early
1970's. Systems to do Holter ECG processing and evaluation are well
known as disclosed in U.S. Pat. Nos. 3,229,687; 4,006,737;
4,098,267; 4,183,354; 4,211,238; 4,316,249; 4,333,475; 4,336,810;
4,633,881; 4,667,682; 4,883,065; 4,989,610; 5,205,295; 5,398,183
and 5,433,209.
[0027] Automated evaluation of ST segment shifts was attempted with
only minor modifications of the basic signal processing and
algorithms used for arrhythmia detection. The ischemia algorithm
compares the voltage at one 8-bits point in the ST segment (located
60 to 100 milliseconds beyond the J point--the junction of the QRS
and the ST segment) to the voltage at another 8-bits point on the
PQ taken as the isoelectric line. Correction for presence of Ta
(atrial ischemia) is unheard off in the current art, since it is
unable to visualize this subtle but important change. Hence, in the
current art, the ST segment (a line and, as such, defined by at
least two points) is represented by a single point. The analytic
paradigm and totally obsolete limitations in computer technology
imposed this major source of false negative reports.
[0028] Identification of the isoelectric line in the ECG is of
paramount importance for detection of atrial and ventricular
ischemia as well as for evaluation of the QT segment and T wave
changes indicative of abnormal repolarization and arrhythmogenic
risk.
[0029] Current Holter algorithms can not detect ECG signs of
abnormal repolarization in a reliable and reproducible manner.
lschemic events, represented by ECG signs of abnormal
repolarization and depolarization, are usually unexpected and
transient. Abnormal repolarization is visualized as microvolt
shifts in the PQ segments (Ta) if atrial or ST segment and T wave
if ventricular. In the current Holter art, Ta is undetected and
mistakenly chosen as the isoelectric point. This false isoelectric
point and spill over of the Ta negative voltage into the ST segment
are common pitfalls that introduce error in ischemia detection by
current algorithms. Down shift of the ST by Ta depends on the
degree of atrial ischemia, the heart rate, atrioventricular
conduction velocity, etc. CVAT can easily recognize such problems
and use the TP segment, instead of the PQ, as the isoelectric
reference line. The TP segment is inscribed from the end of the T
to the beginning of the P waves in two consecutive beats. CVAT can
also identify the influence of Ta into the ST segment and
discriminate false positive up sloping ST depression (starting from
a depressed J point) from up sloping ST depression likely to be due
to ventricular ischemia.
[0030] The prior art taught by conventional Holter monitoring
systems cannot retrieve, store, display or analyze high fidelity
signals in the microvolt or microsecond range. Fast magnetic tape
play back done without optimizing the dynamic range, scanty
sampling, poor quantization and extreme data compression
deteriorate and diminish the signal. However, computer memory (1.2
Megabytes) and processing time are saved and telephonic
transmission of a scanty, low fidelity, low resolution, low dynamic
range signals file is facilitated. Fast Fourier Transformation and
other algorithmic manipulations are used to automate processes,
reduce operator time and level of skill, speed analysis and
decrease cost. All the above contribute to the poor diagnostic
performance of current Holter technology for conditions other than
gross arrhythmia.
[0031] The present invention (CVAT) preferably uses: the best
possible electronic technology for integral signal recovery with
preservation and enhancement of the dynamic range, fidelity, time
and voltage resolution of biologic waves encoded in any recording
media; the best possible computer and signal analysis technology to
digitize the analog biologic signals for storage, further
enhancement, and archival preservation of the signal; and the best
possible electronic, computer and signal analysis technology for
the recovery, display and evaluation of the signals for basic
research, medical and veterinary diagnosis.
[0032] Ambulatory electrocardiography done according to the Holter
technique was used for the initial testing of the CVAT method and
system. CVAT can be used in research, clinical practice and mass
screening as an aid to diagnose cardiovascular conditions which
include, but are not limited to: 1) Myocardial ischemia in all it's
forms; and 2) Repolarization (including but not limited to QT
prolongation and electrical alternans) and depolarization
heterogeneity as signs of increased cardiovascular risk.
[0033] The instant CVAT invention enables extension of Holter
monitoring analysis to the detection and interpretation of ECG
signals at and beyond the microvolt and micro second range. These
minute changes encode important diagnostic and prognostic
information not discernible from current Holter techniques or other
forms of electrocardiographic analysis. Conventional Holter
monitoring and ECG systems cannot detect, preserve or recover
signals at or beyond the microvolt or microsecond range. Exception
is made of techniques limited to the electrophysiology laboratory
not applicable to mass screening or daily clinical practice outside
of specialized centers.
[0034] The CVAT invention provides a method for biologic signal
analysis by trained but not medically skilled technicians. Cost
effective processing is aided by a variety of well identified
morphologic patterns obtained by visual compression, in the X
(time) axes of the played back signal. The visually compressed
patterns are highly suggestive or patognomonic of important
electrocardiographic changes which are confirmed by examination of
the expanded ECG tracing.
[0035] The purpose of algorithms in current use is to provide an
ECG evaluating system, as automated as possible, which scans the
tape as fast as possible with minimal or no operator interaction.
Undue reliance is placed on a physician over reading of very small
depictions of low fidelity greatly deteriorated ECG tracings
recovered from the digital file. Unless the over reader reviews the
whole analog signal encoded in the original recording media (in
addition to editing the computer findings), ischemic and other
events missed by the computer can not be detected. This is the most
common and potentially fatal shortcoming of the current Holter art.
Visual examination of the analog recording is exceptional; it is
done only in very few research centers and not by Holter analysis
services that support clinical practice or research in general.
[0036] Current computerized Holter analysis algorithms use
heartbeat superimposition and template-matching schemes to
recognize departures from normal. Which beats, in a pool of about
100,000 in 24 hours, are the norm for a patient? This is a basic
problem which has to be dealt with even when neural networks, used
in research only, select beats to "train" the computer to recognize
"normal" beats. After digital conversion, each heartbeat becomes a
series of digital values representing XY points of the waveform at
various intervals. In current Holter analysis the number of digital
points per heartbeat is, at best, 33 or lower if the heart rate
goes above 60 beats per minute. The computer does beat matching to
evaluate the difference between values at various points of the
waveform and to compare such values with corresponding points of
templates. A match is defined as any sum of the absolute value of
each of the differences within a preset range. The closest match is
called the matching template. If no template matches, the operator
must classify. The degraded signal preserved by the current art
allows only the grossest matching which cannot go beyond
identification of largely aberrant beats. In addition, current
algorithms include software to analyze the series of waveforms
according to a nondeterministic logic state analysis. This analysis
permits the systems to indicate when waveforms correspond to
ventricular ectopy (VE), bigeminy, VE pair, and ventricular
tachycardia, only.
[0037] A standard waveform has a P wave, a QRS complex and a T
wave. As it is well known in the prior art, the QRS complex is
generally identified by its major peak, usually the R wave. The T
wave is then identified as the first peak after the R wave. A T
wave template is used to process the wave quickly and inadvertent
recognition of a T wave as an R wave is minimized but still exists.
The T wave template is a classification that the operator may apply
when asked to classify the `beat`. Thereafter, any peak that
matches the T wave template is totally ignored, as though no peak
had been found at the position. If the operator incorrectly
classifies a T peak that is or looks like a real beat, that type of
beat will be ignored. Therefore, the method is used as a last
resort, when setting the other parameters does not help, which can
occur with patients who have peaked T waves. Peaked T waves are a
common early manifestation of ischemia. Whenever the ST segment
shifts up or down due to myocardial ischemia, the T morphology is
usually abnormal and not amenable to template classification. While
templates work well for arrhythmia, over reliance in abnormal beat
classification using predetermined templates is a reason for the
poor performance of computer automated Holter analysis in the
diagnosis of conditions other than arrhythmia.
[0038] The template matching method is probably good enough for
ventricular and other gross forms of arrhythmia, which manifest
themselves by millivolt range changes in the QRS. However
superimposition of fast played back, scantily sampled, mercilessly
compressed, filtered, smoothed and/or Fast Fourier Transformed
beats cannot be trusted, since it processes a signal different from
that originally encoded in the magnetic tape. Template detection
may be convenient, but applied to a digital file which lacks
integrity, dynamic range, fidelity and resolution, it cannot be
sensitive or specific nor can it detect abnormalities in microvolt
regions such as the PQ, ST segments or the P and T waves.
[0039] The sophisticated cardiology community is aware of the
current Holter analysis shortcomings; hence, this method is not
routinely used as an aid in the diagnosis of highly lethal
cardiovascular risks.
[0040] The following passage is taken verbatim (bolding added) from
U.S. Pat. No. 5,398,183 issued on Dec. 10, 1990. This algorithm is
widely used in patient care and research and further demonstrates
the disadvantages of current Holter processing techniques.
[0041] "As another feature of the invention, a full disclosure file
representing the entire series of waveforms on the tape is
generated. The file comprises compressed data of limited resolution
and limited sampling rates. The original data is reduced in
resolution by skipping, averaging, or otherwise "decimating"
samples, only using samples at a rate near 33 samples per second
with reference to the patient data. (This is an equivalent rate of
33 samples/sec. of the data generated when the patient was
originally monitored by the analog Holter monitor. Of course, the
data reading rate off the tape is much faster.) In this system 100,
this is accomplished by averaging 4 samples, or by picking one out
of every fourth sample. The data is scaled in amplitude (and
limited) so that the total excursion is 32 levels. The 32 levels
are sufficient resolution to plot on a laser plotter at 200
dots/inch, producing a 0.15" tall waveform. The sample frequency
(referenced to patient) is sufficient to see all R-peaks of normal
beats by position, and to display the waveforms of ventricular
beats sufficiently clearly to be identified. The data is then
further compressed by using a series of coding steps. First the
data is converted to differential coding. (This is a version of
DPCM, `Differential Pulse Code Modulation` in the
telecommunications industry). Each sample has the previous sample
subtracted from it (as the example in FIG. 7 shows). This is a
simple, and computationally efficient means to produce codes which
consist mostly of the smaller integers near 0. In fact, the output
will often have runs of 0s, or +1s, 0, and -1s. Less frequently the
differences will be larger numbers (6 to 31), mostly near the R
peaks. The differential output is limited to the range -31 to +31.
The data is then encoded further using a variation of `Huffman`
coding, or other codes which use few bits for symbols which occur
frequently, and more bits for symbols which occur infrequently.
(The symbols to be coded are the 63 integers in the range -31 to
31). This may be combined with run length coding, which is the
coding of a repeated sequence of the same symbol with a code
representing the sequence in fewer bits than repetitions of the
code representing the symbol singly. The result of this coding is
to bring the number of bits to represent a data point down to
around 2 to 3 bits. This typically allows 24 hours of data to
occupy less than 1 megabyte, where a byte is 8 bits. (3/8 byte/
sample*33 sample/sec*60 sec/min*60 min/hr*24 hr/tape=1.07
Megabyte/tape). This allows the full disclosure to typically be
stored on a single IBM PC compatible 1.2 Megabyte diskette, or
transferred by telephone in 10-20 minutes using the new 9600 Baud
Modems."
[0042] "Taking every third sample provides a limited sampling rate
and scaled differential coding provides limited resolution. Further
compression, such as run length and Huffman coding, may then be
used so that the full disclosure file can be even further
significantly reduced in size. The differential values 0, +1, -1,
+2, -2 may be seen to occur more frequently than the larger values
of 6 to 31 and -6 to -31. If the smaller integer values are
represented by codes using two or three bits, then the size of the
file can be further reduced. FIG. 8 is an example of a part of a
limited resolution, full disclosure file recreated from
differentially encoded, compressed data. The circled areas indicate
ventricular ectopy and supra-ventricular ectopy which is clearly
recognized even though this portion of the file was created from
compressed data."
[0043] The best resolution to be expected with the algorithm
described in this patent are 33 points in the X axes and 32 points
in the Y axes to inscribe one heart beat if the heart rate is 60
beats per minute. If the heart rate goes to 120 per minute there
will be, at best, 16 points to describe the whole cycle length.
[0044] After the "decimating compression" it is only benign to say
that the algorithm driven file will have poor resolution and
fidelity. A 24-hour Holter recording is housed in 1.2 Megabytes,
and yet a 3-minute song, reproduced with any decent degree of
fidelity, takes about 30 to 40 times the memory currently allocated
to a 24 hours Holter recording. This is a grave problem that needs
immediate redress. In contrast, CVAT encodes the same 24 hours
Holter recording in about 350 megabytes. The CVAT file improves the
dynamic range and preserves the integrity, fidelity and resolution
of the signal recorded. It is not surprising that the quality of
the ECG recovered from current Holter analysis algorithms is too
poor to identify anything but arrhythmia with some degree of
certainty. The substantial difference made by CVAT's preservation
and enhancement of the signal has been demonstrated in a
retrospective study done comparing CVAT with the best current
algorithm analysis. The results of this study are provided
below.
[0045] The passage below, taken from the U.S. Pat. No. 4,989,610
issued on Feb. 5, 1991, illustrates problems in another crucial
point of current Holter analysis (bolding added).
[0046] "The first step in this portion of the program reads the six
items contained in the beat time log (BTL) for a particular beat
1220 (see FIG. 55). The data in the BTL is 16 bits wide. It
includes the bin number (to be assigned by the binning operation
(BIN#)), a 32-bit number indicating the time of occurrence of the
beat in terms of {fraction (1/120)} second samples of time (BTH and
BTL), a TEMP location for temporary storage of data, a FLAG word,
an 8-bit ST measurement, and an 8-bit ST-slope measurement."
[0047] "The data representing one channel of the present beat
consists of thirty-two samples. The tenth sample corresponds to the
location of the R-wave, as determined by the beat detection
software. Nine samples preceding the location of the R-wave and
twenty-two samples immediately following the location of the R-wave
constitute the remainder of the samples."
[0048] "Then, the DSP chip 300 performs the Fast Fourier Transform
(FFT) on the thirty-two samples of the channel 1 data, producing
sixteen pairs of real and imaginary data."
[0049] "The pattern describing the members of this first bin are
the twelve points in the complex plane 1236, with each point being
associated with either channel 1 or channel 2 and with one of the
six frequencies. The six pairs of numbers that describe the pattern
for the second and following beats are compared, according to their
channel and frequency, with the groups of points that defines the
bins already in existence. If the twelve points characterizing the
morphology of a beat whose bin is being determined are sufficiently
close, on a point-by-point basis, to the twelve points of an
already existing bin, that beat may be associated with that bin. If
the twelve points describing the morphology of a present beat do
not come sufficiently close to all twelve points describing all
already-existing bin, a new bin is defined. The twelve points
defining the new bin are the twelve points characterizing the
morphology of the most recent beat. The twelve points describing a
beat need not match precisely with the twelve beats defining a bin
for the beat to possibly be placed in the bin. The twelve points
describing the morphology of the beat are sufficiently close to the
twelve points defining the bin if each of the twelve points falls
within windows centered on the points defining the bin."
[0050] The passage teaches that 32 samples represent a heartbeat in
each channel and that these samples are subjected to Fast Fourier
Transform to generate "sixteen pairs of real and imaginary data".
These sixteen pairs of "real and imaginary" data cannot be expected
to fully describe the complex morphology of each heartbeat. With
this algorithm, all the microvolt nuances will certainly be
irretrievably lost. These brief passages provide strong reasons to
render this algorithm useless for anything but arrhythmia
detection.
[0051] The current automated systems for Holter analysis retrieve
only a small portion of the analog signal. Excessively fast play
back speed of the tape, low sampling and quantization rates,
"lossy" and drastic data compression, Fast Fourier Transform to
interpolate imaginary data, filtering, smoothing, etc. are done to
accommodate the need for very small data files suitable for
telephonic transmission and automated analysis. The price paid is
extremely poor ECG data unsuitable for recognition of ischemic and
other dire electrocardiographic signs with any degree of
certainty.
[0052] Myocardial ischemia is the result of oxygen debit in the
heart muscle and conduction system due to increased demand or
decreased supply of oxygen which cannot be fulfilled because of: 1)
organic, fixed, coronary artery stenosis such as that seen in
patients with atherosclerotic plaques in the luminal wall of their
coronary arteries; 2) functional, episodic, often unpredictable
constriction of normal or atherosclerotic coronary arteries; or 3)
clot formation over an atherosclerotic plaque.
[0053] Although spasm was historically suspected to be a cause of
coronary occlusion, from the 1940's to the 1960's the common wisdom
was that atherosclerotic arteries were unable to constrict. In the
70's experts in the field demonstrated that atherosclerotic plaques
are mostly eccentric with a small free arterial wall (opposite to
the atheromatous plaque) likely to cause total occlusion when minor
spasm of such small free wall occurs. When coronary artery spasm
happens, gaps between the endothelial cells happen, collagen
protrusion induces platelet aggregation and in-situ clot formation.
Thrombosis can also lead to partial or total occlusion following
the arterial spastic episode.
[0054] Fixed, organic, atherosclerotic arteries can be readily
identified. The conventional 12-lead electrocardiogram can disclose
patognomonic signs of permanent (not episodic) ischemia of the
heart. The 12-lead electrocardiogram is not expected or designed to
detect transient and unpredictable episodes of myocardial ischemia
or arrhythmia since it depicts only 3 of the 100,000 or more heart
beats we have in 24 hours. For detection of sporadic arrhythmic or
ischemic events, usually triggered by diverse stressful stimuli of
daily living, properly done Holter recording is the only available
method, electrocardiographic or otherwise.
[0055] Permanent (not episodic) myocardial ischemia due to fixed
coronary artery occlusion can be detected by several methods other
than Holter. Electrocardiography and or echocardiography done
during standardized exercise challenge can detect ischemia and/or
arrhythmia induced by physical stress. Other, more invasive
methods, such as drug induced stress testing (the pharmacologic
induction of increased cardiac oxygen demand by administration of
drugs which elevate the heart rate), nuclear radiology or cardiac
catheterization, are designed to detect fixed coronary artery
occlusion.
[0056] All methods available today, other than the Holter
technique, are unable to detect myocardial ischemia due to
transient spastic and/or thrombotic causes of decreased coronary
blood flow. Coronary artery spasm frequently happens without
preceding elevation of the heart rate and/or blood pressure and is
commonly triggered by neurohormonal, emotional and/or environmental
(e.g. exposure to cold, second hand smoking etc) factors, not
inducible in controlled cardiovascular laboratory circumstances.
Hence, this grave condition escapes detection unless Holter
recordings are done under the fleeting and often difficult to
identify forms of daily life stress that induces the attacks in a
given patient. The current Holter recording equipment has enough
fidelity to detect these episodes. The limiting factor is the
current computerized Holter analysis that is unsuitable for
detection of anything but gross arrhythmia. The current art suffers
from false negative findings which have dire consequences for
patients considered healthy when they are not. Today, the only
reliable method to analyze Holter recordings for ischemia is the
direct visual inspection of the analog tape by a competent
electrocardiographist. Such visual Holter analysis is time
consuming and hence, done only in few research efforts and not cost
effective or applicable to daily clinical practice or mass
screening.
[0057] Computerized Holter analysis was designed for the detection
of arrhythmia, and has remained essentially unchanged. Arrhythmia
induces gross changes in the time and voltage domains of the
recording. Algorithms to detect arrhythmia rely on large, millivolt
range. lschemia-induced abnormalities are in the microvolt range
and are unlikely to stand the decimating affects of current
algorithms devoted to minimize file size. Norman J. Holter, Ph.D.
originally designed his valuable method and technology (U.S. Pat.
No 3,229,687. January 1966. Holter et al.) for the study of heart
rate and rhythm. The minor changes introduced by computer
algorithms are not sufficient for reliable detection of ischemia or
risk for potentially lethal arrhythmia.
[0058] In cardiovascular diagnosis, it is important to monitor the
level of the ST segment of the heart beat signal since the
amplitude and direction of the shift correlate well with the oxygen
balance in the patient's heart. A heart receiving insufficient
oxygen experiences predictable anomalies in the ST segment called
"ST Depression" or "ST Elevation". The names relate to the
directional shift (negative or positive microvolts in reference to
the isoelectric line) and shape of the ST segment of the ECG
waveform during periods of insufficient heart oxygenation. The
magnitude and morphologic changes of the T wave are additional
indicators of ischemia which the current algorithms are unable to
detect. The CVAT method makes full use of morphologic changes in
all portions of the ECG to aid in the diagnosis of ischemia and
arrhythmia risk.
[0059] The normal ST segment is located at the isoelectric level
which usually aligns with the PQ or TP segments. PQ segment shift
is frequently due to artifacts or ischemia of the atria (Ta). The
normal condition is generally referred to as the "isoelectric
alignment" of the ST segment. ST segment shifts, measured in
microvolts, above or below the isoelectric line are a reflection of
abnormal myocardial repolarization due to inadequate oxygenation of
the heart. Ischemia not felt by the patient is generally referred
to as "silent ischemia", while ischemia which is painful is called
"angina". All or most ischemic events may be silent. Frequently 80
to 90% of the ischemic episodes can be asymptomatic or have
uncharacteristic manifestations known as angina equivalents.
However, silent or symptomatic, ischemia can equally induce
arrhythmia, myocardial infarction or sudden death. It is suspected
that silent ischemia is the underlying problem in the 50% of
patients who have myocardial infarctions or die suddenly without
having had any premonitory symptoms or signs.
[0060] It is very important to identify the isoelectric line and
the level of the ST segment in the patient's normal heartbeats in
order to be able to properly identify departures from normality.
U.S. Pat. No. 5,433,209 issued on Jul. 18, 1995 includes the
following passage (not direct quotes and bolding not in the
original document):
[0061] For each ECG signal channel, the QRS peak location is
approximated from the point at which a beat is detected over a beat
detection threshold. Then, the ST algorithm backs up 10 samples
from the peak of the QRS complex to approximately land on the PR
interval of the beat wave form. Next, a region of "minimum
activity" is located and the baseline offset, identified as "Base
Corr (i)", is found. The "minimum activity" region is found by
finding the smaller of the two 3-point absolute value derivatives
in a 5 sample window on the PR interval. The baseline offset is
taken for the sample which is located 30 samples forward of the QRS
peak which is thereafter identified as the ST segment. The baseline
offset at the region of "minimum activity" is subtracted from the
sample value at this point and the difference, measured in
millimeters, is taken to be the ST level. Each time a ST level is
calculated, a last eight beats ST level average is also calculated.
Each ST level average during the minute is compared to the last
eight beat minimum and maximum ST level average to find the minimum
and the maximum eight beat average for the minute. Hourly and
monitoring period minimum and maximum ST levels are also determined
in the above fashion. ST level sums are also maintained in the
minute summaries, hour summaries and the end of monitoring period
summary, with the corresponding normal beat counts. The minute ST
level averages are calculated by dividing the minute ST level sum
by the normal beat counts during the minute. The hour ST level
averages are also calculated in a similar fashion. The minimum,
maximum, and average ST levels are each stored as a signed byte of
information. Each value is used along with the gain set for each
channel and the analog to digital range set for each channel in
order to calculate the ST depression or elevation value. Since, the
ST averages all require extensive computations, the computational
load is spread over several periodic interrupt cycles. Minute ST
level averages are monitored over the entire monitoring period to
determine an ST "episode". An "episode" is detected if the minute
ST level average in any channel is at least less than -1.0 mm an
dissustained at this depressed level for more than a minute. ST
episodes of less than -1.0 mm, -2.0 mm, and -3.0 mm and their
duration time in minutes are recorded.
[0062] All these intensive computational niceti es are done on a
digital file known to be incomplete and with major fidelity,
resolution and dynamic range deficiencies. Hence, it is not
surprising that current algorithms miss 9 out of 10 patients whose
ischemia can be identified with visual analysis.
[0063] In the current practice of cardiology, the goal of therapy
for patients with coronary artery disease is being upgraded from
simply controlling anginal pain to a more rational and forward
looking reduction or elimination of silent and symptomatic ischemic
episodes. Any form of ischemia, symptomatic or not, short or long
can kill or induce myocardial infarction. Properly done, the Holter
method is t he only way to detect silent or a typically symptomatic
ischemia and has to play an increasingly important role in the
management of this serious condition. To play that important role
in the detection and monitoring of ischemia the current Holter art
risk of false negative analysis must be eliminated. Biologic signal
analysis can and should make a quantum leap using, electronic
technology, hardware and software developments achieved in the last
decade.
[0064] Sudden cardiac death (SCD) claims over 350,000 lives
annually in the United States; 50% of which had no premonitory
symptoms or signs. SCD usually follows an abrupt disruption of
heart rhythm primarily due to ventricular fibrillation.
Fibrillation occurs when transient triggers impinge upon an
electrically unstable heart causing normally organized electrical
activity to become disorganized and chaotic. Complete cardiac
dysfunction results and may end in sudden death. An episode of poor
oxygenation of the heart (myocardial ischemia) is probably the most
frequent cause of ventricular fibrillation and death.
[0065] A major, and as yet elusive, objective of preventive
cardiology is to detect patients at risk for catastrophic
arrhythmic cardiac events, including sudden cardiac death.
Methodology used to identify subjects at risk must be improved.
Electrical alternans is the electrocardiographic manifestation of
heterogeneous myocardial repolarization and depolarization.
Electrical alternans and ischemia are prominent indicators of risk
factors for major catastrophic or lethal cardiac events. Gradual
microvolt changes are seen in the ST segment and the T wave and are
not as abrupt as the onset of abnormal QRS. Microvolt signals are
easily obliterated by poor dynamic range, "decimating" compression
algorithms, creation of "imaginary" points, etc used by algorithms
in the quest for automation and trans-telephonic transmission of
minimized Holter files.
[0066] Cost effective, non-invasive, techniques for mass screening
and identification of individuals at risk for catastrophic cardiac
events that affect close to 2 million persons per year in the US
alone are needed. Diagnostic technology must be constantly revised
to make full use of the ever improving developments in electronics
as well as computer hardware and software. Prompt risk detection,
will lead to immediate confirmatory diagnosis, interventional
cardiac catheterization, coronary artery by-pass, pharmacologic
management, etc., thereby allowing the saving of hundreds of
thousand of lives in the world. There is need to develop an
improved Holter analysis that can be cost effective in time and
level of operator skill and still precise enough to avoid
potentially catastrophic false negative reports.
[0067] Advent of Holter analysis as a reliable method to detect
ischemia and risk for severe arrhythmia will also facilitate
targeted new drug development by providing valid objective
therapeutic end points, instead of unreliable surrogate end-points.
Cutting age technology has to be used to preserve the fidelity,
dynamic range, time and voltage resolution of the recorded signal,
a step of paramount importance for the accurate diagnosis of
electrocardiographic abnormalities in the microvolt region. Holter
analysis obsolescence is the medical counterpart of the Y2K problem
with the difference that it's cost in mortality and morbidity is
orders of magnitude greater than the Y2K can ever be. This problem
is greatly reduced, if not completely solved, by the teachings of
the present invention.
[0068] The use of the instant invention to process analog
electrocardiographic signals makes it possible to evaluate every
single beat of the ambulatory electrocardiogram by compacting the
signal in a manner that will disclose sui-generis visual patterns
which correspond to and readily identify classic, discrete
anomalies of the electrocardiogram, described by experts in the
field as part of pathologic conditions compromising the
cardiovascular system. The understanding of these patterns make it
possible to identify the abnormal elements of the
electrocardiogram.
[0069] The immediate value to mankind provided by the instant
invention is that it makes possible identification in a
non-invasive and cost-effective manner, patients who have silent
myocardial ischemia and hence are at high risk for myocardial
infarction, sudden death and other catastrophic events. About one
half of patients with myocardial infarction, sudden death, lethal
arrhythmias, etc. are patients who have no history of coronary
heart disease and are probably carriers of silent myocardial
ischemia, which triggers the terminal events leading to the
patient's demise. The instant invention enables timely discovery of
this covert condition and enables timely anti-ischemic therapy
which will result in the saving of millions of lives as well as a
decrease in hospital use, disability and improvement of the quality
of life of those affected by silent ischemia a potentially lethal
condition.
[0070] As explained in detail above, instead of visual analysis,
computer programs implementing mathematic algorithms are presently
routinely used to perform analysis of electrocardiograms in an
attempt to detect abnormalities therein. Such computer programs
have had only limited success in diagnosing pathological conditions
which compromise a patient's cardiovascular system. Due to their
cost-effectiveness, however, such mathematical techniques are
widely used today. As a result, many patients have had pathological
conditions go undetected.
[0071] Thus, a need exists for improved methods and systems which
enable improved detection of pathological conditions during
analysis of the electrocardiogram and other waves of biological
origin.
[0072] The instant invention advantageously uses algorithms and
computer programs created for the purpose of editing, manipulating
and/or analyzing sonic and/or electromagnetic waves, such as music
processing programs.
SUMMARY OF THE INVENTION
[0073] A primary object of the instant invention is to increase the
accuracy and decrease the cost of biologic signal analysis for use
in mass screening, clinical practice and research.
[0074] The instant invention, referred to herein as the
Computerized Visual Analysis Technique or "CVAT", generally relates
to the use of up-to-date signal processing technology with
state-of-the-art electronic and computer technology for the
evaluation of biologic signals obtained from isolated cells,
tissues, human and animal species to aid basic research and
diagnosis of medical and veterinary disease states. CVAT can be
used to process biologic signals such as, but not limited to:
[0075] The electrocardiogram in all it's forms, and in particular,
the continues electrocardiographic signal such as that obtained
with the Holter technique or during on-line, real time monitoring
of a patient.
[0076] The electroencephalogram
[0077] The myogram
[0078] The phonocardiogram
[0079] Respiratory sound waves including their correlation with the
electrocardiogram and encephalogram to diagnose sleep disorders in
the hospital and in out of hospital settings, etc will be
evaluated.
[0080] The invention also enables the generation of a report of the
evaluation and the triggering of alarms in the real time monitoring
mode.
[0081] CVAT is different from current forms of biological signal
analysis in that it preserves the integrity of the analog signal,
enhances dynamic range, the fidelity and resolution of the original
signal obtained. All these features lead to better interpretation
of the signal using compressed visual patterns, which, in turn,
leads to quick and easy identification of abnormalities suggestive
of pathologic states. CVAT is based on the application to
biological signal analysis of advances made in the software,
hardware and electronic technology used to process and analyze
sound waves. This is a major departure from current obsolete ways
to digitize analog signals, which include the use of extreme lossy
digital compression, Fast Fourier Transformation and other
mathematical and autocorrelational engineering based algorithms
which markedly deteriorate the quantity and quality of the signal
to be evaluated.
[0082] A main application of the present invention is to improve
the analysis of the Holter electrocardiogram. The invention departs
from the current Holter ambulatory electrocardiogram analysis in
that it replaces auto-correlational communications engineering
techniques and quantification-dependent analysis of the
electrocardiogram done with obsolete computer technology which
eliminates most of the original signal and distorts the fidelity,
resolution and dynamic range of the small fraction kept in the
digital file for algorithm driven analysis.
[0083] Instead, CVAT relies on morphologic and pattern evaluation
signal analysis complemented with quantification when necessary.
The totality of the signal originally recorded is preserved with
protection and enhancement of dynamic range, resolution and
fidelity of the signal.
[0084] The following features represent the main aspects of the
instant CVAT invention, and together enable the invention to
provide optimal processing and analysis of biologic waves:
[0085] Prior to analog to digital conversion, each lead of the ECG
or other biologic signal undergoes electronic enhancement of the
dynamic range;
[0086] Analog to digital conversion is done with the best possible
equipment and the slowest possible play back speed of the
originally recorded signal;
[0087] An optimum quality sound card is used for analog to digital
conversion using the highest possible sample (preferably 44,100 Hz
per second per channel or higher) and quantization (preferably
16-bits per sample per channel or higher) rates;
[0088] Digital sound processing software and techniques are used
for the processing and analysis of biological signals. The inventor
has determined that one suitable sound processing software is SOUND
FORGE, which is designed for processing digital audio. Other
similar software programs (such as, but not limited to
seismographic and geologic software) used for wave analysis may
also be used in accordance with the present invention. Such
software allows various steps to be performed to enhance the signal
(without introducing distortion) in the voltage and time domains
and enhances pattern visualization and other forms of analysis;
[0089] The invention preferably used file formats originally
created for sound wave applications (such as, but not limited to
.wav and other similar file extensions) to process the biological
signals;
[0090] Computer sound cards (such as but not limited to the Montego
Bay card) are used to code and decode the analog biologic
signal;
[0091] Visual compression of the analog signal is used to display
the signal with high fidelity, resolution and dynamic range to
identify visual patterns used as indicators of abnormalities which
can be confirmed by expanding the signal;
[0092] Use of visual pattern libraries to train technicians with
low level skills to facilitate the cost effective use of CVAT for
mass screening, clinical practice and research;
[0093] Use of time interval measurements in the biologic signal to
asses internal functional harmony as a reflection of normality or
pathology. Such time intervals can be measured with a precision at
or below 10,000.sup.th of a millisecond and will be even more
reliable when better recording techniques are introduced. Normal
standards applicable to the method used will be created to replace
normal values extrapolated from data obtained with better equipment
and in different circumstances. Extrapolated quantitative standards
lack precision; and
[0094] Use of screen capture software (such as, but not limited to,
Paint Shop Pro) to document the findings of the analysis and to
transfer the images to graphic processing programs (such as but not
limited to Adobe PhotoShop). This software is used for
magnification and preparation of the report of the analyses.
[0095] In accordance with another aspect of the invention, internal
harmony in the duration of different intervals of the
electrocardiogram is advantageously used, and relies more on
relative than on absolute duration. Internal harmony is done to
evaluate repolarization of the myocardial cell according to the
relationship between:
[0096] Cycle length duration measured as the J-J interval
[0097] Total duration of ventricular repolarization measured as
[0098] J-Te and related to cycle length as (J-Te/J-J).times.100
[0099] Transmural repolarization time measured as Tp-e related to
the total duration of ventricular repolarization as
(Tp-e/J-Te).times.100
[0100] In accordance with another aspect of the invention, the
method is used to detect microvolt and lesser changes in the ST
segment, T wave, etc., as an indication of myocardial ischemia or
electrical alternans or non-homogeneous repolarization and/or
depolarization in ambulatory, cost effective conditions.
[0101] In accordance with another aspect of the invention, the
method is used for evaluation of microvolt and lesser changes in
the PQ interval shown as Ta changes suggestive of atrial
ischemia.
[0102] In accordance with another aspect of the invention,
morphologic patterns are used to detect transient or intermittent
myocardial ischemia when other forms of Holter analysis are useless
in evaluating recordings with artifacts, bundle branch block,
ventricular hypertrophy, previous myocardial infarctions, etc.
[0103] In accordance with another aspect of the invention,
morphologic patterns are used to detect intermittent
atrioventricular or intraventricular blocks potentially caused by
cardiac pathology such as, but not limited to, ischemia.
[0104] In accordance with another aspect of the invention, the
method is used to detect traditionally minor (less than 1 mm shift
in the current art) considered "non-specific" ST segment shifts as
sign of important ischemia risk. This is done by correlating the ST
shift to the QRS as percent of the preponderant wave of the QRS
normalized to its maximum potential using the CVAT software
described herein.
[0105] In accordance with another aspect of the invention, the
method is used for on-line monitoring of the electrocardiogram and
other biologic signals.
[0106] In accordance with another aspect of the invention, the
method is used to analyze simultaneously obtained upper airway
breath sounds and the electrocardiogram to detect sleep apnea at
home or elsewhere.
BRIEF DESCRIPTION OF THE DRAWINGS
[0107] These and other objects, features and advantages of the
instant invention will become apparent from review of the following
detailed description with reference to the accompanying drawings,
in which:
[0108] FIG. 1. Shows waves and segments of the
electrocardiogram;
[0109] FIG. 2. Shows inaccuracy of the voltage calibration signal
in current Holter recordings;
[0110] FIG. 3. Shows examples of voltage calibration differences
across and within Holter recordings;
[0111] FIG. 4. Shows evaluation of ST segment shift as percent of
the QRS;
[0112] FIG. 5. Shows calibration and voltage changes during a
recording;
[0113] FIG. 6. Shows examples of voltage optimization in a
recording done without enhancing the dynamic range;
[0114] FIG. 7. Shows an expanded view of FIG. 6 to show visually
identifiable electrical alternans;
[0115] FIG. 8. Shows visually compressed CVAT pattern to illustrate
normal elements thereof;
[0116] FIG. 9. Shows examples of CVAT patterns compatible with ST
segment elevation and depression;
[0117] FIG. 10. Shows expanded ECG showing ST elevation and T wave
changes;
[0118] FIG. 11. Shows a CVAT pattern of ST depression and T wave
inversion;
[0119] FIG. 12. Shows a CVAT pattern compatible with ischemia
showing slow onset and offset of the ST shift;
[0120] FIG. 13. Shows expanded ECG to illustrate Ta, ST depression
and T wave inversion;
[0121] FIG. 14. Shows a CVAT pattern of brief period of ST
depression;
[0122] FIG. 15. Shows ST shift which becomes apparent only after
voltage optimization;
[0123] FIG. 16. Shows a CVAT pattern of ST depression and atrial
flutter;
[0124] FIG. 17. Shows ST depression and atrial flutter in an
expanded ECG;
[0125] FIG. 18. Shows a CVAT pattern of intermittent 2.sup.nd
degree atrioventricular (AV) block;
[0126] FIG. 19. Shows 2.sup.nd degree AV block in an expanded
ECG;
[0127] FIG. 20. Shows a CVAT pattern of ST elevation and
intraventricular conduction delay;
[0128] FIG. 21. Shows intraventricular conduction delay (ICD) and
ST elevation in an expanded ECG;
[0129] FIG. 22. Shows intermittent, shifting ICD;
[0130] FIG. 23. Shows a P wave marching on the T wave visible
through voltage optimization;
[0131] FIG. 24. Shows an example of resampling and voltage
optimization;
[0132] FIG. 25. Shows beat to beat change on T wave morphology;
[0133] FIG. 26. Shows ST depression in the beats opposite to those
in FIG. 25;
[0134] FIG. 27. Shows an example of ST depression and biphasic T
waves;
[0135] FIG. 28. Shows ST depression in the recording from which
FIG. 27 was taken;
[0136] FIG. 29. Shows biphasic T waves;
[0137] FIG. 30. Shows Ta, ST depression and elevation in the
recording from which FIG. 29 was taken;
[0138] FIG. 31. Shows expanded and magnified ECG to show double
hump T wave;
[0139] FIG. 32. Shows marked and quick change in T wave
morphology;
[0140] FIG. 33. Shows continues tracing to show beat-to-beat
changes in T wave morphology prior to a premature beat;
[0141] FIG. 34. Illustrates use of the calibration signal to find
the number of samples per second of clock time during the recording
period;
[0142] FIG. 35. Illustrates measuring cycle length in a resampled
and voltage optimized tracing;
[0143] FIG. 36. Shows expunged QRS to magnify microvolt range
waves;
[0144] FIG. 37. Shows measuring of J-Te;
[0145] FIG. 38. Illustrates reason for algorithm failure to measure
biphasic T waves;
[0146] FIG. 39. Shows time conversion to measure pacemaker
function; and
[0147] FIG. 40. Shows pacemaker triggered beats evaluated.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0148] As described below, all the steps of the CVAT method, the
electronic equipment, hardware and software used are preferably
selected and devoted to the preservation and enhancement of the
dynamic range, fidelity, resolution and integrity of the biological
signals being processed. Compact visual analysis is done on an
optimum analog signal retrieved preferably using the best possible
technology. Various steps are taken to enhance visualization and
facilitate analysis to aid basic research, medical and veterinary
diagnosis. The quantity and quality of the signal is protected
during analog to digital conversion using techniques such as: 1)
independent electronic channel dynamic range modulation; 2) slowest
possible play back speed of the magnetic tape; and 3) maximum
possible sampling and quantization rate.
[0149] For the same reason, digital compression, smoothing of the
data, filtering, Fast Fourier Transformation etc., are preferably
avoided to preserve the integrity and quality of the biological
signal. The CVAT methodology, electronic equipment, hardware and
software used in accordance with the instant invention are
preferably upgraded over time to keep pace with the fast
development of signal analysis electronics and computer
technology.
[0150] The following described equipment and software are
preferably used when implementing the CVAT method to process and
analyze the Holter ambulatory electrocardiogram.
[0151] A Denon cassette recorder model 770 R for the slow play back
of the cassette tapes in which the 24 hr electrocardiogram was
recorded. The right and left channel outputs of the cassette deck
being connected (using high quality, well shielded RCA type cables)
into the input jacks of a Stereo Sound Mixer.
[0152] A Radio Shack SSM-60 Stereo Sound Mixer, wherein the cable
connected to the right channel output of the Denon cassette deck is
fed into the right channel input of the CD Line 2 jack in the audio
mixer. The cable connected into the left channel output of the
cassette deck is fed into the left channel input of CD Line 1 in
the audio mixer. The fading slider in the Audio Mixer is preferably
placed exactly in the middle position to feed equal signals from
Line 1 and 2 into the audio mixer output jack. High quality, well
shielded RCA cables are preferably used to connect the right and
left channel output jacks of the audio mixer using an RCA to mini
(3.5 mm) stereo jack conversion piece into the stereophonic input
of a sound card.
[0153] A high quality sound card is preferably used, such as (but
not limited to) the Turtle Beach Montego A3D 64 Voice PCI Sound
Card installed in a Dell mini tower. This card has greater than 90
decibels signal to noise ratio, sampling rates as high as 96 kHz
per channel at 16-bit per channel digital, coder/decoder software
for recording and play back of high fidelity, high resolution, high
dynamic range signals. Another sound card installed in a Gateway
Solo 9100 Multimedia Notebook has also been determined by the
instant inventor to provide suitable functionality for use with the
instant invention.
[0154] Windows 98 PC platforms are preferably used, such as a Dell
Dimensions XPS R400 MHz PENTIUM Mini tower with MMX technology with
348 MB SDRAM memory and a Gateway Solo 9100 Multimedia Notebook
with a Pentium MMX 266 MHz and 192 MB of RAM. It is noted, however,
that any other suitable computer platform me be used in accordance
with the instant invention.
[0155] In accordance with an important aspect of the instant
invention, software dedicated or otherwise used for signal analysis
of waves including, but not limited to, software used in the
processing of digital sound, seismography, identification of
extraterrestrial radio waves, etc. is advantageously used to
process the biological signal. The instant invention is applicable
to the use of all different combinations of programming,
mathematical analysis techniques, etc., devoted to the retrieval,
storage, display, analysis, etc., of biological waves indicative of
the function of any and all organs or tissues, intact or isolated
from human or other biologic species. Such processing of biological
waves includes retrospective (e.g. analysis of ambulatory
recordings of electrocardiograms or electroencephalograms), as well
as real time analysis of a stream of signals such as (but not
limited to) continues monitoring of electrocardiograms or
encephalograms. The CVAT method is dedicated to preserve the
integrity and enhance the dynamic range, fidelity, resolution, and
other important parameters of such waves.
[0156] In accordance with the invention, use of existing (and
future) digital audio processing programs, such as Sound Forge XP
(offered by Sonic Foundry, 754 Williamson St, Madison, Wis. 53703)
and all the like sound processing and editing programs are
advantageously applied to the analysis of biological waves. Sound
Forge XP has been determined by the inventor to work well in
connection with the method described herein. Other similar software
programs for use in PC, Apple, Linux, Unix and any other computer
platforms may also be used.
[0157] It is noted that Sound Forge supports an extensive set of
file formats dedicated to digital audio editing and processing.
Historically, almost every type of computer platform used it's own
file format for audio data, some files are more generally
applicable, and conversions between almost any pair of formats is
possible, but losing information is a risk. The invention
advantageously uses any of these or similar file formats for the
specific use of biological wave analysis. Examples of some of the
files which can be used are:
[0158] Active Streaming Format (.ASF)
[0159] Ad Lib Sample (.SMP)
[0160] Amiga SVX (.VSX/.IFF)
[0161] Covox V8 (.V8)
[0162] Creative Labs VOC (.VOC)
[0163] Dialogue VOX (.VOX)
[0164] Gravis Patch (.PAT)
[0165] InterVoice (.IVC)
[0166] Macintosh AIFF (.AIF/.SND)
[0167] Macintosh Resource (.SND)
[0168] MIDI SDS (.SDS)
[0169] NeXT/Sun(Java) (.AU/.SND)
[0170] Raw Files (.RAW/.*)
[0171] Real Media (.RM/.RA)
[0172] Sample Vision (.SMP)
[0173] Sonic Foundry Sample Resource (.SFR)
[0174] Sound Designer 1 (.DIG/.SD)
[0175] Sounder/Sound Tool (.SND)
[0176] Video for Windows (.AVI)
[0177] Wave (.WAV) etc
[0178] The signal analysis software is used in accordance with the
instant invention to code and decode (codec) the biological waves
as well as to retrieve, display, process and analyze biological
waves for basic research, medical and veterinary diagnosis.
[0179] The analog signal retrieved from the source is displayed, in
the analog compressed (compacted) or expanded formats, using
maximum fidelity, resolution, color depth and refresh rates. A
cathode ray tube (Dell Computer) as well as a liquid display system
(Gateway Solo notebook) were used. Both and all-future forms of
compacted or compressed analog display of digital data in the
fashion described herein may be used whether it is from
retrospectively obtained (e.g. from any recording media) or real
time signals from patients, animals, isolated organs, tissues,
cells, etc.
[0180] To document and preserve findings displayed on the screen,
to further magnify the signal or subject it to image enhancement,
etc., a screen capture software program is preferably used, such as
Paint Shop Pro 5. Photoshop 5 may be used to process the image,
enhance contrast, enter legends, further magnify etc. Microsoft
Word and Microsoft Publisher are preferably used for the
preparation of reports to summarize the findings of the signal
analysis. JPEG encoded images may inserted within the text. The
above and similar programs and digital image files for the
different processes needed for visual or instrumented analysis,
image enhancement etc of the analog signal representing biological
waves processed using digital sound or other wave technology
process are preferably used. The images obtained can be printed
using, for example, an inkjet Hewlet Packard Printer Model
1120C.
[0181] The CVAT method of the instant invention is designed to
process and analyze biological waves using digital sound or any
other computerized wave analysis software or techniques, including
but not limited to the use of digital audio acquisition, editing,
reproduction etc., as tools to facilitate computer aided visual as
well as algorithmic and mathematical analysis. The purpose of CVAT
is to enhance the use of signal analysis as an aid to basic
research, medical and veterinary diagnosis. The CVAT method of the
instant invention preferably includes, but it is not limited to,
the following sequential steps:
[0182] Transferring the analog signal from the original media into
the computer hard drive. This is preferably done using the best
possible electronic equipment, enhanced dynamic range and optimum
play back speed.
[0183] Using computer software for high sampling and quantization
rates (at least 44,100 Hertz at 16 bits per sample, per channel
where the sampling rate is the number of frames per second), to
preserve the dynamic range, integrity, fidelity and resolution of
the analog signal encoded in the original recording media.
[0184] Allocation of optimum amount of computer memory to preserve
the integrity, dynamic range high fidelity and resolution of the
signal. Digital compression algorithms, filtering, smoothing or any
other signal deteriorating or diminishing manipulation likely to
compromise the integrity, fidelity, resolution and dynamic range of
the original analog signal are preferably avoided at all times.
[0185] CVAT is preferably done with the high quality hardware
(codec chips, etc.) and software to code and decode the analog
signal to recover and display it in a high fidelity-high resolution
mode in a computer monitor at or above 1600.times.1200 pixels with
32-bit color and high refresh rate.
[0186] CVAT is preferably done using a high quality computer system
to magnify waves in the X and Y-axes. Magnification along the X and
Y-axes is done to allow precise measurement beyond microvolt and
microsecond levels to facilitate visual morphologic analysis in the
compressed or expanded modes. Enhanced resolution, fidelity and
dynamic range further facilitate detection of morphologic changes
of biologic waves such as the ECG, encephalogram, miograms, etc.
Since its discovery at the beginning of this century,
electrocardiography has been a visual pattern recognition
discipline. Computers can be used to facilitate such pattern
recognition but in final analysis trained technicians are still
superior to computers to discriminate normal from abnormal
patterns.
[0187] Use of high quality programs for screen capture and further
image processing of selected representative portions of the
recordings is also an integral part of CVAT.
[0188] Each of the above-mentioned steps will be described in
greater detail below. The caveat is that keeping pace with the fast
improvement in electronic equipment, computer hardware and
software, the tools and techniques used in each step of this method
will continue to improve and translate technologic advances to the
benefit the different patient populations served by CVAT. For
instance, 24-bit quantization as well as 192 kHz sampling rates are
envisioned to soon become an integral part of the CVAT
technology.
[0189] The invention may also employ Direct Stream Digital (DSD)
technology for the analysis of biological waves for basic research,
medical and veterinary diagnosis. DSD uses Delta Sigma modulation
to generate a bitstream that represents the analog signal being
recorded. Instead of sampling the signal at a particular instant
determined by a converter clock, the DSD converter does something
quite different. It keeps the previous sample in memory (actually
in a feedback loop, since the system does not record signal levels)
and monitors the waveform as it continues to change. If the signal
value is higher than that of the previous sample, the converter
records a one, if not, it records a zero. In this manner, full
positive signals are represented by a string of 1's and full
negative signals by a string of zeros. Silence (or the isoelectric
line in the ECG or EEG) is represented by alternating ones and
zeros. It is not linear pulse code modulation. The density of the
pulses represents the instant amplitude of the signal. Since DSD is
not organized into 16 or 24 bit samples, DSD simply records the
bitstream itself and it is and looks "analog-like". DSD claims 120
dB signal-to-noise ratio through what is known as noise shaping.
The DSD analog/digital converter uses 64 times oversampling
achieving four times the density of current music CDs recorded at
44,100 Hz and 16-bit quantization. This technology will allow
simultaneous processing and analysis of up to 72 channels (signal
streams) for use in CVAT analysis of electroencephalograms and
12-lead electrocardiograms.
[0190] The invention is, for example, applicable to analysis of 24
hours ambulatory electrocardiograms recorded with current art
Holter technology. The CVAT Holter analysis aims to find
classically described electrocardiographic signs compatible with
silent, atypically symptomatic or symptomatic ischemia, a major
cause of morbidity and mortality. Detection of Risk for lethal
arrhythmias is also improved by CVAT. Ischemia is probably the most
common cause of lethal arrhythmia and sudden death. Hence,
electrocardiographic signs of increased risk of serious arrhythmia
(such as depolarization and repolarization heterogeneity and
preservation of the within patient harmony of the repolarization
periods) are described herein. CVAT may also be used to detect
increased risk of arrhythmia and sudden death in patients with
congestive heart failure (CHF).
[0191] Cassette format magnetic tape is still the most commonly
used media to record the ambulatory electrocardiogram from leads
attached to a patient. To facilitate 24 hr recording without
changing cassettes, the tape transport speed is slowed to 1.1 or
0.55 mm (depending on the manufacturer) per second instead of the
55 mm per second used to record music or other sonic waves.
Differently from current Holter analysis and to preserve the
quality of the analog electrocardiographic signal, CVAT technology
uses as-slow-as-possible play back speeds. As described above, a
Denon cassette deck model 770 R that normally plays back at 47.6 mm
per second may be used. This model has variable play back speed.
For CVAT, the slowest play back speed is preferably used at a
transport tape rate of 40.4 mm per second. Hence, Holter tapes
recorded at 1.1 mm per second are preferably played back at 36.7
times real time. In CVAT, slow play back speed is an important step
in the preservation of the fidelity and resolution of the signal
during the analog to digital conversion of the file. The slow speed
used in CVAT should be compared to the much faster play back speeds
used in current Holter analysis to accelerate analog to digital
conversion despite deterioration of the signal quality. Current
Holter analysis play back speeds between 60 and 480 times real
time, 240 and 480 times real time are probably the most common play
back speeds.
[0192] CVAT preferably uses 44,100 and 96,000 Hz-16 bits per
channel as the standard sampling and quantization rates. At 44,100
sampling rate, a single sample is taken every 0.000023 seconds of
clock time. A 24 hr Holter recording (more than 100,000 heart
beats) is digitized by conventional art using, at best, 8,000 Hz
samples per second followed by drastic lossy compression schemes
that reduce the digital file to about 1.2 megabytes. The same file
is encoded by CVAT in 350 megabytes, using 44,100 Hz, 16-bits
quantization and no compression schemes. This 1.2/350 ratio in the
richness of the digital file is a reflection of the difference in
sampling and quantization rates, tape play back speed, and the
use-no use of "lossy" digital data compression.
[0193] The sampling rates used by current Holter analysis are
frozen in the early 90's and are, at best, 8,000 samples per second
of clock time. When fast play back speed is factored in, the result
is about 33 samples per second recorded time if the play back speed
is 240 times real time. In CVAT at sampling rates of 44,100 or
96,000 Hz there are 1,188 to 2,376 per second of recorded time
respectively.
[0194] Even the recently introduced flashcard technology is
subjected to the artificial limitations imposed by the desire to
transmit compressed data over telephone lines. An ambulatory
recording system with 500 samples per second, 10 bits per sample,
three channels, and 24 hours recording, requires the storage of
about 162 MB. To accommodate this data on a 20 MB flash memory card
requires a compression ratio of 8:1 or higher. However, the
perceived need for transtelephonic transmission limits the flash
card files to about 8-MB which require more drastic compression
schemes and/or 8-bit quantization. The signal retrieved is still
incomplete and of poor quality.
[0195] Conversion of the analog signal to digital format is a
crucial step which determines the final quality of the signal
preserved for analysis. Neither the magnetic cassette play back
speed or the sampling rate undergo modulation to compensate for
acceleration of the heart rate which are likely to happen during
the recording period. The number of digital samples per heartbeat
of the ECG can be referred to a normal heart rate of 60 beats per
minute or one heart beat per second of recorded time. The table
below compares the number of digitally sampled points per heart
beat using current Holter analysis art at different play back
speeds and CVAT at two different sampling rates
1 SAMPLES PER PLAY BACK POINTS PER SECOND SPEED HEART BEAT* CURRENT
8000 240 .times. REAL 33 PER HB ART TIME CURRENT 8000 480 .times.
REAL 16.6 PER HB ART TIME CVAT 44,100 36.7 .times. REAL 1201.6 PER
HB TIME CVAT 96,000 36.7 .times. REAL 2615 PER HB TIME *Digital
data points available to reconstruct one ECG cycle length (one
heartbeat) at 60 beats per minute
[0196] In the time domain, at 60 beats per minute, the current
Holter art has, at best, only 2.7% of the sampling points of the
lowest CVAT rate (33 vs 1,201 points per heartbeat). The fastest
(and probably most common) sampling rate used in the current Holter
art has only 0.61% of the time points CVAT offers (16.6 vs. 2,615).
Hence, starting with the analog to digital conversion and prior to
any of the other data degrading steps, the current art deletes
between 97.3 and 99.39% of the signal encoded in the magnetic tape.
The data loss increases with increasing heart rate. If the heart
rate goes from 60 to 120 per minute, only one half of the above
points will be converted from the analog to the digital format and
enter the computer file. For the current Holter analysis, this loss
happens prior to further signal degradation due to lossy
compression, replacement of real for imaginary points (through Fast
Fourier Transformation), filtering, etc which is not the case when
CVAT is used. This data elision is compounded by the current Holter
analysis use of 8-bit instead of 16-bit cards. Quantization with
8-bit cards gives only 0.39% (256 points per channel) of the
voltage resolution afforded by 16-bit cards (65,536 points per
channel). This calculation does not include the signal
deteriorating effect of failure to do independent control of
dynamic range prior to digital conversion.
[0197] The importance of quantization rate and independent channel
gain control for the preservation and enhancement of dynamic range
will now be described. It is being increasingly recognized in
electrophysiology of the heart that microvolt level and lesser
magnitude voltage changes encode very important diagnostic and
prognostic information. Current computerized 25 Holter analysis
sacrifices dynamic range, fidelity and resolution to high-speed
analog to digital conversion and the need to fit the 24-hr signal
in a small digital file to facilitate telephonic transmission. It
is well known that lack of dynamic range affects foremost the lower
voltage changes in the signal. If dynamic range is not optimized
prior to digital encoding of the analog signal, the range of
voltage describing points above and below the isoelectric line is
not fully utilized; hence the ST-T changes in the ECG are less
apparent. A primary difference between CVAT and the conventional
art is that CVAT strives for the preservation and enhancement of
the dynamic range to facilitate identification and interpretation
of microvolt and lesser voltage changes used to detect ECG signs of
potentially lethal conditions. Independent channel modulation of
the dynamic range, slow tape play back, high sampling and
quantization rates achieve optimum storage, recovery and display of
microvolt range signals. CVAT is preferably done with 16-bit
quantization rate, but 24-bits and higher may also be used. The
signal to noise ration at 16-bits per sample and 44,100 Hz is about
90 dB. Current Holter analysis use of 8-bits quantization drops the
signal-to-noise ratio to 40 dB or less. Noise is known to induces
more interference in the quieter periods in music and around the
isoelectric line and the ST-T region of the ECG. Signal smoothing
and filtering done in current Holter analysis further deteriorate
discrimination of microvolt range changes in the signal.
[0198] In CVAT independent electronic gain control is possible
because morphologic analysis relies on the internal harmonic
relationship of the electrocardiographic waves and relative rather
than quantitative changes in the signal. Microvolt measurement in
current Holter analysis is based on numerical conversions using
voltage calibration (1 millivolt=10 mm deflection) signals which
often are faulty and hence unreliable. In CVAT, independent
electronic gain is adjusted in order to use the Y-axes to it's full
extent with the QRS deflection as (or near) 100% of it's potential
height. This is done to expand the dynamic range and to obtain the
greatest possible benefit of the 16-bit quantization rate. By
optimizing dynamic range prior to digital conversion, as much of
the potential 65,536 points available per channel in the Y-axes are
used. High dynamic range and resolution in the Y-axes facilitates
evaluation of microvolt and lesser voltage changes in the ECG.
These steps are essential for the detection of ischemia and
arrythmogenic risk. Current Holter analysis does not optimize
dynamic range prior to digitizing at 8-bits per sample. these
results in only partial use of the 256 points provided by 8-bits in
the Y-axes. Hence, the effective difference in dynamic range
preservation and voltage resolution between the conventional art
and CVAT is well beyond 65,536/256. Hence, the current Holter
quantization has 0.39% of the resolution offered by CVAT
quantization rate. Additionally, during CVAT analysis a voltage
optimization (VO) bit interpolation process can be used to magnify
the Y-axes. Voltage optimization can be applied to selected regions
of the visually compressed file, individual heartbeats or selected
waves within it. Voltage optimization takes the selected part of
the signal to 100% of it's potential above or below the isoelectric
line. In the current electrocardiographic art, reliable detection
of microvolt changes is confined to costly and time consuming
techniques such as signal averaging done in the electrophysiologic
laboratory and not useful for mass screening or applicable to
Holter analysis. Detection of certain types of microvolt changes is
valuable as tool to identify serious risk for arrhythmia. Such
changes are usually more evident at times of physical and/or
emotional stress. Ambulatory detection of microvolt changes,
applicable to mass screening is now made possible by CVAT and
should result in major improvement in cardiovascular diagnosis for
prompt intervention and important reduction of mortality and
morbidity.
[0199] Current Holter analysis relies upon signal amplitude
(voltage) calibration done prior to recording by introduction of a
1 millivolt signal directly into the magnetic tape. In theory this
calibration signal should be equal in both channels and should
render an even 10 millimeters deflection when visualized in the
electrocardiogram. If all goes well, a 1 mm (0.1 mV) shift of the
ST above or below the isoelectric line is to be taken as an
electrocardiographic sign of ischemia. This concept is a direct
extension of the very long experience with exercise tolerance
testing done with stationary 12-lead electrocardiographs, more
precise instruments than the average Holter recorder. In 12-lead
electrocardiographs, the electronic gain can be adjusted at the
time of calibration. In current Holter art, gain adjustment in the
recorder is not possible. The Holter recorder calibration signal
frequently has significant variation within and across recorders
and it does not give as reliable conversion factor for microvolt
evaluation as the 12-lead electrocardiographs.
[0200] FIG. 2 shows an example of uneven calibration signal in a
Holter recording. The size of the QRS voltage in the lower lead
could be 4.4 or 3.1 mm depending on which part of the calibration
signal would be chosen to represent 1 millivolt as a 10 millimeters
deflection.
[0201] FIG. 3 shows the difference in the size of the calibration
signal obtained from 3 different recordings, also note the
difference in the height of the signal in the lower channel of
Holter C.
[0202] Reliance on the calibration signal to quantify the severity
of microvolt range changes around the isoelectric line is not as
precise and useful in Holter recording as it is in 12-lead
electrocardiography. Conversion based on unreliable calibration
hampers within and most importantly across patients comparisons.
Furthermore, the voltage of the electrocardiographic waves does not
remain constant during the 24 hr Holter recording period. Voltage
changes may be due to physiologic (e.g. positional, respiratory
cycles, etc) as well as pathologic reasons (ventricular distention
and mechanical incompetence of the ischemic ventricle is an
important reason for change). Under these conditions, absolute
quantification of the ST segment, using the calibration signal as
valid gage, may lead to erroneous conclusions. This is probably a
reason for the poor performance of current Holter analysis in
detection of myocardial ischemia.
[0203] More than 20 years ago, Marvin Ellestad M.D. called
attention to the importance of judging ST segment shifts as a
percent of the QRS in the same heartbeat. This work has been
recently quoted in Ellestad M; American College of Cardiology
Educational Highlights; Summer 1998: 15-21 from which FIG. 4 was
taken. This figure is used by Ellestad to emphasize the importance
of describing ST segment deviation as a percent of the major
deflection in the respective QRS. Ellestad observation is the
product of intensive and classic work in exercise stress testing
done with 12 lead electrocardiographs, better and more reliable
instruments than Holter recorders. Ellestad suggested 10% shift of
the ST as the cutoff point for the diagnosis of ischemia. However
recent data ("Association of Nonspecific Minor ST-T Abnormalities
With Cardiovascular Mortality", Daviglus M. L. et al. JAMA. 1999;
281:530-536) indicates than even lower degrees of ST shift are
likely to carry increased risk of mortality and morbidity. In CVAT
voltage changes are evaluated as percent of the dominant spike in
the QRS deflection for which voltage is optimized to 100% of it's
potential. Using CVAT, non-cardiology trained technicians can
detect ST segment shifts as small as 2% of the QRS.
[0204] The CVAT methodology for detection of myocardial ischemia
using ST segment shift will now be described. Evaluation of the ST
segment in isolation leaves most of the repolarization events out
of diagnostic consideration with consequent loss of valuable
information. Most of the epicardial, and all the endocardial and
mesocardial repolarization data are not encoded in 60 to 100
milliseconds of the ST segment adjacent to the J point. To be able
to properly evaluate the T wave in the standard 12 lead ECG, it is
necessary to increase the paper recording speed from 25 mm per
second to 100 mm per second. The voltage gain must be doubled to
inscribe 1 mV as a 20 mm deflection using a well maintained and
calibrated electrocardiograph. ECG recordings done in this manner
have enough detail to visualize all the repolarization nuances,
especially, T wave morphology.
[0205] Current computerized Holter analyses compares only two 8-bit
points. One 8-bit point in the ST segment (placed 60 to 100 ms
beyond the J point) is compared to an 8-bit point in the PQ segment
which is taken to be the isoelectric line without regard or
correction for the presence of atrial ischemia (Ta). This is done
with strict quantitative adherence to the 1 mm shift (compared to
the calibration signal) concept derived from 12-lead
electrocardiography. Current Holter analysis considers less than 1
mm shift as being normal, this results in a high rate of false
negative Holter reports when algorithm analysis is not compared to
visual analysis of the analog signal by expert cardiologists.
Current computerized Holter analysis does not do morphologic
evaluation of the T wave. In current Holter analysis the digital
ECG file is not a complete and accurate representation of the
originally encoded analog signal. To properly evaluate the ST
segment and the T wave it is imperative to have a high fidelity and
resolution signal with optimum dynamic range. The ECG signal
recovered by CVAT has enough detail in the microvolt region to
render precise details for accurate evaluation of all the ECG.
Current Holter algorithms lack detail in the data stored and do not
have the means to render a faithful depiction of the T waves
recorded in the magnetic tape.
[0206] In Holter analysis, unreliable voltage calibration and
unexpected voltage changes during the recording render the 1 mm
shift at one point in the ST segment a handy but imprecise
extrapolation from 12 lead electrocardiography. It will be a major
improvement to evaluate the ST segment shift as what it is, a line,
and not a single point as current algorithms do. The extent of the
shift from the isoelectric line is best described as a percent of
the largest voltage element of the QRS, as proposed by Ellestad
more than 20 years ago. CVAT is able to do a thorough evaluation of
the ST segment and complement it with a complete morphologic
evaluation of the T wave, a major index of myocardial
repolarization. CVAT can quickly identify shifts as small as 2%
above or below the isoelectric line. Traditionally, minor changes
in the ST segment and the T wave have been dismissed as "non
specific" and without prognostic or diagnostic importance. However,
recent data ("Association of Nonspecific Minor ST-T Abnormalities
With Cardiovascular Mortality", Daviglus M. L. et al. JAMA. 1999;
281:530-536) link these "minor" abnormalities to increased
mortality risk.
[0207] FIG. 5 shows the difference between the 1.sup.st and
2.sup.nd calibration signals in the lower lead as well as the
marked voltage differences found within the recording period.
Quantification of the ST segment shift will depend on which complex
is taken as a gage; the changing QRS voltage is another source of
error. The morphology of the T wave is a valuable confirmation of
abnormal repolarization which is not used by current computerized
Holter analysis. The recording from which this figure was taken was
not processed with voltage or dynamic range optimization.
[0208] FIG. 6 show a minor example of the advantage of voltage
optimization in a recording digitized without optimizing dynamic
range. In FIG. 6, a "minor" (less than 1 mm) ST segment depression
in the lower lead becomes evident and important after the signal is
voltage optimized in the lower lead. Current Holter analysis would
consider this to be a non-diagnostic ST shift. The morphology of
the inverted T wave, which has a fast inscribing initial limb that
makes it symmetric and arrow-point-like (best seen in alternating
beats), validates the ischemic nature of the ST depression. The
alternating morphologic difference (arrow point like versus
slightly rounded top) in the T waves is suggestive of
repolarization heterogeneity probably due to ischemia. Two
consecutive voltage optimized T waves from the lower lead are
further magnified in FIG. 7. In this figure, the ST shift is more
evident in the second beat and the morphologic differences in
consecutive T waves are obvious. Flutter waves are seen as the
downward small spikes going down from the isoelectric line.
Detailed morphologic analysis of a high fidelity enhanced quality
signal is possible with CVAT and impossible with conventional
Holter algorithms. With CVAT, much greater degrees of magnification
than shown above are possible if necessary.
[0209] The visual compression and morphologic evaluation of the
ambulatory electrocardiogram will now be described. CVAT visual
analog signal compression is a powerful tool to expedite and add
precision to Holter analysis. FIG. 8 is CVAT's visually compressed
pattern of a normal ECG tracing showing the different components of
the compressed signal. This recording was done without optimizing
the dynamic range prior to analog to digital conversion. Most of
the lower lead has been voltage optimized and it shows the
difference CVAT does when applied to a recording done without
independent channel modulation of the dynamic range. Normally, the
P, PQ, J, ST, T and TP (PT band) are superimposed to each other to
form a solid band in the middle of the visually compressed analog
signal. The QRS band surrounds the PT band as a lighter component
where the individual heartbeats can be seen. The density of the QRS
band increases and decreases with increasing and decreasing heart
rates respectively. The QRS also shows the regularity or
irregularity of the heart rate in characteristic patterns which
allow quick recognition of a single heart beat blocked (dropped).
Pathology such as intermittent conduction defects, sick sinus node
(tachy-brady) syndrome atrial flutter, fibrillation, etc have
distinctive patterns in the QRS band. The best rate of visual
compression depends on the sampling rate and heart rate. It ranges
between {fraction (1/64)} to {fraction (1/256)}. The lowest rates
of compression works best when the heart rate is fast or when the
sampling rate is low and vice versa. Expansion of the pattern in
the window with resampling to higher rates or limitless
magnification, whenever necessary, allow precise identification of
classic electrocardiographic signs.
[0210] FIG. 9 is a composite of different recordings shown examples
of how CVAT compressed analog displayed facilitate quick
identification of ST segment shifts by technicians without
biomedical training or skills in electrocardiography. The upper
lead shows compact patterns of ST depression. The PT band is seen
with a solution of continuity in it's middle portion. The white
area which hugs the isoelectric line is composed by the PQ and
portions of the T (depending on the changes in T morphology) and
TP. The lower band which moves into the negative voltage area
represents down shift of the J point, ST and portions of the T
(depending of the morphology of the T wave). The black space
separating the PT band into two diverging portions is patognomonic
of ST shift. In the lower lead examples of ST elevation are
collected. Notice that the arm of the bifurcated PT band which
departs from the isoelectric line has moved into the positive
voltage area denoting ST segment elevation. A library of patterns
can be used for training technicians who will do CVAT analysis.
Expansion of this tracings show the classic signs of ischemia
described in the PQ for atrial ischemia and the J point to the end
of the T wave for ventricular ischemia. Transient conduction
blocks, which can be secondary to ischemia, also have
characteristic patterns.
[0211] FIG. 10 shows ST segment elevation and T wave changes in an
expanded view used to confirm the findings on the compressed
pattern. FIGS. 11 and 12 show visually compressed patterns of
episodes of ST depression with inversion of the T wave. FIG. 11
shows best the gradual onset and offset of the ST segment shift
characteristic of a true ischemic episode. FIG. 13 shows an
expanded view of ST depression with inverted T wave. FIG. 14 shows
a short episode of ST depression with T inversion. This episode
most likely would not have been detected with conventional Holter
analysis. If detected, it would have been dismissed since it does
not last one minute which is a convention for acceptance of an
episode in current Holter analysis. FIG. 13 also shows Ta as a sign
of probable atriai ischemia. This ECG sign is not commonly seen
because of the lack of dynamic range, fidelity and resolution of
current ECG tracings.
[0212] FIG. 15 shows non-consecutive segment (two beats each) from
a recording done without independent gain modulation. In both
leads, the first wave is the 1 mV calibration signal followed by
pairs of consecutive beats taken from different parts of the
recording. The first beat of each pair is as it was originally
recorded (O) and the second (V) is voltage optimized using CVAT
software. Both the upper and lower leads are similarly treated. The
5.sup.th pair in the lower lead, which has the lowest QRS voltage
in the original signal, is the one which shows the most distinct ST
segment elevation in the voltage optimized beat in the lower lead
and depression in the opposite lead. The ST elevation can not be
seen in the original beat. If we quantify the S wave in the
original beat of the 5.sup.th pair according to the calibration
signal, this S wave would be about 6 mm in total and the ST
elevation would not be equal to the 1-mm criterion. However the
voltage optimized, second beat of the 5.sup.th pair, shows that the
ST elevation is about 20% of the S wave. This figure shows well the
constant variation in the QRS voltage for which there is no
adjustments possible in the calibration-based ST shift quantitative
approach.
[0213] In FIG. 16, the QRS band shows the regular irregularity of
the heart rate due to atrial flutter in a patient who also has ST
depression. Both are readily identified in the visually compressed
CVAT pattern.
[0214] FIG. 17 is an expanded tracing of the pattern showing atrial
flutter and ST depression; the flutter waves are visible showing a
4:1 ventricular capture rate. This degree of visualization of the
ECG is not possible with conventional Holter analysis.
[0215] Next, intermittent atrioventricular and intraventricular
conduction defects are described. The conduction system is
relatively more resistant to ischemia than the rest of the
myocardium; hence when it is affected enough to show conduction
blocks, a severe degree of ischemia must be suspected.
Atrioventricular and intraventricular blocks can be readily found
using CVAT. The nature of the conduction abnormality can be further
defined by expanding and magnifying the signal if necessary. In the
compressed CVAT mode, conduction blocks have characteristic
patterns.
[0216] FIG. 18 shows the compressed CVAT pattern of intermittent
second degree AV block. The QRS band in the right size of the
figure has gaps which resemble a comb with broken teeth. FIG. 19 is
an expanded view of this record in which the second-degree
atrioventricular block is readily visualized. Two P waves are
identified, the first does not conduct to the ventricle, and the
second triggers a ventricular contraction. The pattern is repeated
in consecutive cycles. Independent channel gain was not used in
this recording.
[0217] FIGS. 20 and 21 show the visually compressed and expanded
patterns of ventricular ischemia (ST elevation) and
intraventricular conduction delay. Atrial ischemia (Ta) is readily
apparent in FIG. 21.
[0218] FIG. 22 shows alternating intermittent intraventricular
conduction defect (ICD) in the 1.sup.st beat of the upper lead and
the second beat of the lower lead. The beats are not contiguous,
are placed next to each other for comparison only. This patient had
changes in the upper lead alternating with changes in the lower
lead, suggesting a shifting location of the ischemic area of the
heart. Note the widened QRS and the initial slurring of the
deflections in the 1.sup.st upper and 2.sup.nd lower beats. Compare
these beats with their counterparts in the opposite leads which
have a near normal configuration. Note also that the T waves
following the beats with abnormally conducted QRS have a different
configuration of the T waves compared with the other beats. The
abnormal T waves reflect the disarray in repolarization consequent
to the aberrant intraventricular conduction in the preceding
QRS.
[0219] Current Holter algorithms lack integrity, dynamic range,
fidelity and resolution and can not match human ability to
recognize morphologic patterns. For these and other reasons,
current Holter analysis can not benefit from the wealth of ECG
signs of ischemia and it is limited to dubious quantification of
one point in the ST segment. CVAT is designed to identify all the
valuable electrocardiographic signs described in the peer-reviewed
literature (mainly from studies done in exercise testing
laboratories) to improve Holter analysis and facilitate ischemia
detection.
[0220] T wave morphology changes as sign of abnormal repolarization
will now be described. Current Holter analysis algorithms rely on
mathematical formulae which use calculated slopes and intersects in
an attempt to identify electrocardiographic landmarks that are
difficult to precise even with visual magnification of specially
taken 12 lead ECG's. Analog reconstruction of the T wave with
current algorithms is poor due to lost data, and poor fidelity,
resolution and deterioration of the dynamic range of the scanty
signal preserved. Morphologic evaluation of incomplete
electrocardiographic signal of poor quality is questionable, at
best. The low quality of the highly compressed and filtered ECG
signal encoded by the current Holter algorithms does not permit
retrieval of the analog electrocardiogram as it was encoded in the
magnetic tape. CVAT recovers the intact signal and enhances it to
create a rich digital file using state-of-the-art software
dedicated to preservation of the dynamic range, high fidelity and
resolution. CVAT can accurately magnify at will both the time and
voltage domains rendering ECG's of optimum quality suitable for all
kinds of measurements and morphologic evaluation.
[0221] The four beats in the upper and lower rows of FIG. 23 are
the same beats, duplicated from the same lead. This portion of the
file has been resampled from 44,100 Hz to 96,000 Hz in both rows.
In the Y-axes, the voltage has been optimized in the lower row
only. Note, in the lower row, the marching of the P wave into the T
wave (second beat) to merge with the T in the third beat. This kind
of evaluation is not possible with current Holter algorithms.
[0222] Repolarization abnormality is a harbinger of potentially
lethal arrhythmia (see "Electrical Alternace" below) myocardial
infarction, or sudden death. Abnormal T wave morphology suggests
myocardial intracellular changes which alter orderly, normal,
cardiac cell repolarization. Abnormal repolarization can be a
consequence of abnormal depolarization or ischemia and the cause of
serious arrhythmia.
[0223] Under normal conditions, the T wave has the same polarity
than the QRS deflection. Inscription of the T wave starts when the
plateau of the action potential of the epicardium separates from
that of the mid myocardial cells (mesocardium). As the voltage
gradient between the epicardium and the mesocardium continues to
expand, the ascending limb of the T waves is inscribed in the ECG
at a slower rate than the descending limb of the T wave. The
ascending limb inscribes the peak of the T wave when the epicardium
is fully repolarized. In the opposite side of the ventricular wall,
the plateau of the endocardial cell action potential separates from
that of the mesocardial cell generating an opposing voltage
gradient that limits the amplitude of the T wave and starts
inscription of the descending limb of the T wave. The full
repolarization of the mesocardium marks the end of the T wave. The
time elapsed from the peak to the end of the T wave is an index of
the degree of transmural dispersion of repolarization. A
disproportionate prolongation of the action potential in the
mesocardium prolongs the time from the peak to the end of the T
wave (Tp-Te) and widens the T due to slower rate of descent of the
distal limb. This prolongation of the Tp-Te may be also out of
phase with changes in the R-R interval; i.e. it does not shorten or
elongate proportionally when the heart rate increase or decrease,
respectively.
[0224] The internal harmony of repolarization intervals will now be
described. When electrocardiographic intervals are measured to
assess repolarization, the standard reference for comparison is
correction to an "ideal" heart rate of 60 beats per minute. More
important than this comparison is the lack of pari passu shortening
of repolarization with shortening of the cycle length. The
corrected QT (QTc) interval is considered a surrogate of the
cellular action potential duration. The QT interval includes
electrical depolarization and repolarization of the ventricles and
is a limited reflection of the complex electrogenesis of
ventricular repolarization. The QTc has been shown to be of no
value to predict mortality or arrhythmic events (Circulation 1998;
97:2543-2550). A study (J Am Coll Cardiol 1987; 10:1313-21) in
which 19 automated QTc measurement systems were compared found
standard deviations as large as 30 ms when locating the end of the
T wave compared with 6 ms for the QRS onset. This study compared
recordings done with conventional 12-lead electrocardiographic
equipment. The inferior quality of the Holter recordings would give
similar or greater standard deviations if subjected to the same
type of study. Any evaluation of T wave duration is complicated by
the T wave changing morphology within a recording period. Valid
diagnostic conclusions can not be based on imprecise landmarks,
measurements "normalized" with formulae established for more
precise and complete signal obtained with superior type of
equipment and when the standard deviation of the method is probably
larger than the elongation supposed to be clinically
significant.
[0225] There are researchers who believe that T wave morphology is
more important than its total duration. The duration of
repolarization usually changes in unison and in harmony with the
duration of each heartbeat. Harmonic change is probably more
important for diagnosis and prognosis than milliseconds of
difference in "corrected" QT. The concept of measuring the interval
between the peak and the end of the T wave as a measure of
ventricular repolarization has been proposed several years ago
(Antzelevitch et al J Am Col Cardiol; 1994; 23:259-77). This time
interval represents the transmural dispersion of repolarization:
the longer it is the more fragmented and abnormal repolarization is
likely to be. Evaluation of the morphologic features of the ST
segment and the T wave, looking for manifestation of electrical
alternans, assessing the internal coherence of the repolarization
intervals and their concordant change with heart rate variation are
more valuable than the simple determination of the QTc.
[0226] The instant CVAT method proposes that better measurements of
repolarization and its accommodation to changing heart rate
are:
[0227] Duration of repolarization measured from the J point to the
end of the T excluding the QRS since this complex reflects
ventricular depolarization.
[0228] Time from the J point to the end of the T (J-Te) reflects
epicardial, mesocardial and endocardial repolarization time
[0229] Tp-e stands for the time from the peak (Tp) to the end (Te)
of the T wave as an expression of ventricular transmural
repolarization time
[0230] Time from J point to J point (J-J) as a measure of one heart
beat duration
[0231] (Tp-e/J-Te).times.100 represent the relative duration of
transmural repolarization time as a percent of the total duration
of the repolarization. Prolongation of the transmural
repolarization, in disproportion to the total duration of
repolarization, is likely to reflect transmural repolarization
dispersion, prolongation of the vulnerable period and heightened
risk for ventricular arrhythmia. This percent value, determined
continuously or at regular intervals (such as every 15 to 60
minutes) plotted, in the Y-axes, against clock time of Holter
recording, in the X-axes, represent circadian variation in the
relative duration of transmural repolarization.
[0232] (J-Te/J-J).times.100 express the relative duration of total
repolarization time (epicardial plus transmural) as part of total
cycle length and correlates total repolarization to heart rate.
Normally, J-Te should shorten as J-J shortens. Plotting this
percent value versus clock time will give an idea of the circadian
variation in total repolarization time as part of it's own cycle
length (and hence heart rate) from which valuable diagnostic and
prognostic information could be derived.
[0233] Preliminary data suggests that normal repolarization (J-Te)
may be at or below 30% of the cycle length (J-J) and transmural
(epicardial to endocardial) repolarization (Ta-Te) should also be
at or below 30% of J-Te. Further work is being done by the instant
inventor to further precise these relationships.
[0234] In FIG. 24, the two consecutive beats in the upper row were
copied in the lower row. The ECG signal was resampled from 44,100
to 96,000 Hz, in both leads. Only the lower lead was voltage
optimized. This process can be used to expand the time and voltage
domains for precise identification of electrocardiographic
landmarks. In this figure, the T wave has a symmetric (arrow point
like) shape, different from normal where there is a slower
ascending than descending limb. The J-J is 791.5 ms (heart rate=76
beats per minute). J-Te is 237.5 ms, Tp-e is 50 ms. Hence, the
transmural repolarization (Tp-e) is 21% of the total repolarization
time (J-Te) and the total repolarization time (J-Te) is 30% of the
total cycle length (J-J).
[0235] In FIG. 25, two consecutive beats are duplicated in the
lower row, both were resampled, only the lower row was voltage
optimized the cycle length is 1054.1666 ms (heart rate=56.9 beats
per minute). The first T wave J-Te is 279 ms; Tp-e is 96.6 ms or
34.6% of J-Te. The second T wave J-Te is 291.6 ms; Tp-e is 83.3 ms
or 28.5% of J-Te. The relative longer duration of the transmural
repolarization of the first T wave (Tp-e of 34.6% vs. 28.5% of
their respective J-Te) coupled with the distinctly different
morphology and height (the first T is 2.5 times taller and more
peaked than the second) suggest heterogeneous repolarization
(electrical alternans).
[0236] FIG. 26 shows the opposite lead to that shown in FIG. 25,
the two beats opposite to those shown in FIG. 25 have been
isolated. Significant horizontal ST segment depression is shown.
Electrical alternans and heterogeneous repolarization may be caused
by myocardial ischemia.
[0237] In FIG. 27, ST segment depression and biphasic
(+-configuration) T waves are present in both leads. The cycle
length (J-J) is 783.3 ms (heart rate=76, 5 beats per minute), J-Te
is 458.33 ms, Tp-e is 195.83 ms. Transmural repolarization (Tp-e)
takes 42.7% of the total repolarization time (J-Te) which
represents 58.5% of the cycle length (J-J). The relative
prolongation of both the total and the transmural repolarization
times is in keeping with the ST segment depression seen in both
leads. Current Holter analysis would have placed the end of the T
at an intersect with the isoelectric line based only on a line fit
onto the down sloping arm of the first (positive) phase of the
biphasic T. The negative phase of the biphasic T would have been
excluded by the placement of the slope. Furthermore, its unlikely
that the degraded signal would have shown the negative phase of the
biphasic T. The ST segment depression has an upsloping trend;
however, the ST fails to return promptly to the isoelectric line.
The morphology of the ST in conjunction with that of the T wave
strongly suggests ventricular repolarization abnormality probably
due to ischemia.
[0238] FIG. 28 is a tracing from the lower lead of the recording
shown above a little later in the recording period. Distinctly
horizontal ST segment depression with T wave inversion is
documented which confirm the likelihood of myocardial ischemia in
this patient.
[0239] The T waves in both leads of FIG. 29 are biphasic. In the
lower lead J-J is 912.5 ms (HR=65.7 bpm), J-Te is 458.3 ms (50.2%
of J-J) and Tp-Te is 270.1 ms; hence, 58% of the total
repolarization is taken by transmural repolarization. ST segment
depression in the upper lead and elevation in the lower lead are
also present.
[0240] FIG. 30 is a tracing taken later in the same recording as
FIG. 29. Compared with the previous figure, note the more
pronounced horizontal ST depression in the upper lead and the ST
elevation in the lower lead, confirmation of myocardial ischemia in
this patient.
[0241] FIG. 31 shows three heartbeats in the same lead duplicated
and resampled. Only the lower tracing was voltage optimized. The T
wave has double hump morphology. This tracing raises the question:
Is the transition from epicardial to endo-mesocardial
repolarization at the peak of the first hump?
[0242] FIG. 32 shows two heart beats (1stB and 2.sup.nd B) located
in the same recording, same lead, 20 seconds apart. The 1.sup.st
and 2.sup.nd QRS constitute one cycle length and the 3.sup.rd and
4.sup.th, the second cycle length.
[0243] The following measurements were taken from the first cycle
length in FIG. 32:
2 J-J 770.83 ms (77.8 beats per minute) J-Te 362.50 ms (47.0% of
J-J) Tp-e 187.50 ms (51.7% of J-Te)
[0244] For the second cycle length:
3 J-J 883.33 ms (67.9 beats per minute) J-Te 406.25 ms (45.9% of
J-J) Tp-e 220.83 ms (54.3% of J-Te)
[0245] The positive phase of the biphasic T wave in the second beat
is 4.3 times (apex of the T to the isoelectric line) taller than
the T wave which follows the first QRS. The double hump morphology
shown in FIG. 31 was observed in the same recording of the
patient.
[0246] Work is ongoing by the instant inventor to further identify
additional morphologic patterns, internal correlation of intervals
and voltages in normal subjects and patients with different
cardiovascular pathology as well as during percutanoeus
transluminal coronary artery balloon dilatation.
[0247] The electrical alternans will now be described. Temporal
heterogeneity in repolarization can be expressed in an individual
beat (spatial heterogeneity seen as repolarization dispersion
comparing the same ST-T in two or more different leads) or in a
sequence of beats (dynamic heterogeneity shown as differences in
duration and/or amplitude) also known as electrical alternans.
Electrical alternans represents heterogeneity of cardiac muscle
repolarization and/or depolarization as a consequence of myocardial
ischemia and other forms of cardiac disease. It can be considered a
harbinger of malignant arrhythmias.
[0248] Beat-to-beat microvolt alternation of the amplitude,
unstable morphology and/or changing polarity of the T wave are
markers of vulnerability to potentially lethal ventricular
arrhythmia. There are research efforts to identify patients who
have this electrocardiographic risk marker using sensitive spectral
signal-processing techniques in specialized laboratories, by highly
skilled electrophysiology experts. Electrical alternans documented
during exercise induced tachycardia is a better predictor of
arrhythmia vulnerability than signal averaged electrocardiography
(Estes NA et al. Am J Cardiol 1997; 15:1314-8) or
electrophysiologic testing in the cardiac catheterization
laboratory (Hohnloser S H et al J. Cardiovasc Electrophysiol 1996;
7:1095-111).
[0249] FIG. 33 is a 16 seconds consecutive strip from a recording
analyzed with CVAT. Macroscopic beat-to-beat variation of the T
wave morphology is noticeable; especially the peculiar morphology
of the T wave that precedes the premature beat (PB). CVAT allows
visual identification of beat-to-beat T wave morphologic changes
which correspond to microvolt beat-to-beat variations in
repolarization. Current Holter analysis lacks signal quality and
quantity to match CVAT accurate morphologic analysis. CVAT brings
into daily clinical practice a diagnostic tool heretofore available
only as a costly experimental tool in few research laboratories and
not yet applicable to patient care or large scale risk screening,
both possible with CVAT.
[0250] Measuring time intervals in the Holter electrocardiogram is
now discussed. As it is the case with data on microvolt range ECG
signals, knowledge on electrocardiographic time intervals is the
result of studies and experienced acquired using well maintained,
standardized and calibrated stationary 12-lead electrocardiographs.
Concepts arrived at in this manner were extended to Holter
analysis. However, the following are some of the reasons to believe
that the 12-lead ECG intervals are not necessarily applicable to
the evaluation of ambulatory electrocardiography:
[0251] Holter recordings are done with relatively simple,
battery-driven motors which run at very slow speeds without
feedback regulation of the speed drive. The magnetic tape runs
across the recording head at critically low speeds of 1.1 to 0.55
mm per second. Ten percent fluctuations in speed are said to be
common in Holter recordings, and probably a 3% variation is the
best that can be expected with the best equipment available today
which is not used outside of few research centers. This factor of
error in the conversion from time in the recording to real (24 hr)
time is usually not accounted for. Servo control and closed loop
technology can improve the steadiness of the tape transport speed
at the critically low speeds needed but have not yet been
incorporated into commercial Holter recording. The instant inventor
is researching better technology and media to be used for the
ambulatory recording of biologic waves.
[0252] Very fast play back of Holter recordings done at critically
low speeds are another factor for the potential distortion of the
time intervals and variation both within and across equipment
used.
[0253] Tape stretch, wow, flutter, tape biasing etc. are likely to
introduce more problems leading to less than precise determination
of the duration of the intervals in the ambulatory
electrocardiogram.
[0254] In current Holter analysis, duration of the QT and other
intervals is measured in milliseconds. CVAT technology can measure
down to one 10,000.sup.th of a millisecond of real time in
recordings digitized at 44,100 or 96,000 Hertz per second.
Recordings digitized at 44,100 Hz can be resampled at 96,000 Hz.
Sampling rates higher than 96,000 Hz are being tested. Lacking
steady recording speed during Holter recording, absolute time
measurements have to be interpreted with caution as useful to judge
relative duration of different elements within a recording, but
difficult to extrapolate and compare across recordings or across
patients. Hence, in CVAT, internal concordance, as an expression of
harmonic relationships within the electrocardiographic intervals of
a given patient, is considered more important than absolute time
measurements. It is believed that judging intervals relationship as
an expression of harmonic continuity of electrophysiologic cardiac
function is more useful than "correcting" time intervals using
formulas developed for 12-lead electrocardiography. Basset's QTc
and other formulas correct the QT interval using as reference
"normal" population intervals at an ideal heart rate of 60 beats
per minute. The formulas were derived from and for 12-lead
electrocardiography. Critically low recording speeds, variable play
back rate, tape stretch, wow flutter etc do not exists as factors
of error in 12-lead ECG interval measurement. Hence, correction
factors developed for 12-lead ECG are probably unsuitable for
application to conventional Holter analysis.
[0255] Until better Holter recording equipment (e.g. with servo
controlled recording speed and with precise 10, 100 and 500 Hz
calibration) will be commonly available, the advantages of the CVAT
mode of analysis can be applied to Holter recordings done with
currently available equipment.
[0256] The 1 millivolt per second signal used today can be a used
as a gage to measure time intervals. Across patient and across
recorders comparisons may not be as precise as CVAT can be, but
search for within a recording harmony of time intervals can be done
until better recording equipment will be available.
[0257] Using Sound Forge, a window is opened to record 5 to 10
seconds of silence (a blank canvas) at identical sampling rate than
that used to store the analog signal into the hard drive. The input
format used should be samples per second. A 12 to 15 cycle length
calibration signals is copied into the canvas from the middle or
most stable part of the calibration period in the recording to be
analyzed. Any beats, or waves within a beat, which need to be
measured are also copied from the recording being analyzed into the
canvas.
[0258] The first step is to expunge the areas of each beat which do
not require precise duration measurement. Unless there is a need to
measure QRS duration it is best to eliminate the QRS from the
canvas. If not expunged, the height of the QRS becomes an obstacle
for maximum magnification of the P and T waves using the voltage
optimization feature of CVAT. Magnification of the P and T waves
using pixel interpolation is a great aid for precise identification
of the beginning and end of the waves. Resampling to a higher
sampling rate expands the time domain and adds precision to time
intervals measurement. Using CVAT time intervals can be measured to
the 10,000 th of a millisecond.
[0259] FIG. 34 shows a canvas in which the signal in the upper
channel was copied into the lower channel for the purpose of
demonstration of the steps described above. Both channels were
resampled from 44,100 to 96,000 Hz. Only the lower channel was
voltage optimized. The record calibration voltage waxed and waned
in height between 68 and 100%. This is a reason not to trust
voltage measurements from Holter recordings. Six calibration cycle
lengths on either side of the tallest signal in a period located
about the middle of the calibration segment were transported into
the canvas. In FIG. 34, 10 calibration cycle lengths were isolated;
cursors were placed at the apex of the first and last signal with
the recording opened at 1:1 scale for best visualization and
precise placement of the markers. The 10 cycle lengths measured as
23,274 samples; hence
One cycle length=1 second=2,327.4 samples.
[0260] This is the constant used to calculate the time periods in
this recording and in the FIGS. 35 to 38.
[0261] FIG. 35 shows one heartbeat with the cursors placed at the
apex of two consecutive R waves with the screen opened at 1:1
ratio, to fit the figure into a size suitable for reproduction, the
window was contracted to 1:2 ratio. There were 2,153 samples from R
to R, hence 2,153/2,327.4=0.9250665 seconds which gives an
instantaneous heart rate of 64.86 beats per minute.
[0262] To obtain the full benefit of voltage optimization of the P
and T waves, the central portion of the QRS was excised in FIG. 36.
After voltage optimization the tracings were further magnified to
best visualize the microvolt components of the ECG and allow
precise identification of the T and P morphology. The small sharp
spikes between the P and the T waves are the take off of the R wave
and the return to the isoelectric line of the S wave. These
landmarks have been left to identify the PR and J points
respectively, as noted in the figure.
[0263] FIG. 37 is a close-up of the beat used to calculate the
instantaneous heart rate in FIG. 34. Cursors were placed at the J
point and at the end of the T wave (Te) located visually with the
window opened at 1:1 scale. Precise placement of the cursor at the
end of the T was verified as the intersect of end of the negative
phase of the biphasic T with a line traced from the beginning of
two consecutive P waves taken as the isoelectric line. The number
of samples from the J point to the end of the T wave were 1,163
which divided by the number of samples for one second (2,327.4)
equals 0.4996992 seconds.
[0264] FIG. 38 shows time measurement from the apex of the T (Tp)
to the end of the T (Te) for the same beat in a 1:1 scale. Tp-Te
equals 692samples divided by the constant 2,327 equals 0.2973274
seconds for mesocardial and endocardial repolarization time. FIG.
38 also shows the difference (black area) that would exist between
an automated slope based T wave measurement and CVAT. The
algorithms for automated QT interval measurement from Holter tapes
would fit a slope on the descending limb of the positive (first
half) segment of the biphasic T wave. By doing so the algorithms
would disregarded the 450 samples of the negative phase of this
biphasic T. A slope based measurement would have resulted in 450
samples, or 0.1933488 seconds, shorter T wave (J-Te at 0.3063504
seconds instead of 0.4996992 seconds), a greater difference than
that between normal and pathologic states
[0265] JT dispersion and circadian variation and relationship with
R-R (J-J) changes can be measured by selecting 5 to 10 beats at
regular intervals depending on the purpose of the measurement.
Within the constrains imposed by variation in the tape recording
speed, CVAT gives a better measurement of time intervals than
current algorithms.
[0266] Next, the evaluation of implanted pacemakers function in
accordance with CVAT will be described. The high fidelity, high
dynamic range of CVAT makes it suitable for pacemaker function
evaluation.
[0267] FIG. 39 shows an excerpt of one lead of a recording showing
calibration signals and paced beats. The average duration of one
cycle length of the calibration signals is 992.5 samples, which is
to be taken as being equal to one second in this recording. The
time between the first and second pacemaker spike is 979 samples
divided by 992.5 equals 0.9863979 seconds. There are 14 samples
from the beginning of the pacemaker spike in the 1st beat to the
apparent take off of the ventricular depolarization which equals
0.0141057 seconds. The 4th ventricular depolarization is not
pacemaker triggered and happens at 0.6811083 seconds (676samples)
from the previous pacemaker spike. The 5.sup.th ventricular
depolarization is pacemaker triggered at 1.0448362 seconds from the
onset of the non-pacemaker triggered ventricular depolarization. It
seems that the 5.sup.th pacemaker spike happened when spontaneous
ventricular depolarization had just started similarly to the
8.sup.th depolarization which started 1.0508816 seconds after the
onset of the spontaneous 7.sup.th depolarization in this series of
consecutive paced and non paced beats. FIG. 40 is a close up of
these paced beats. To the best of the inventors' knowledge, this
kind of evaluation is not possible with current Holter
algorithms.
[0268] CVAT's application to on-line electrocardiographic
monitoring in intensive care areas will now be described. It is
known that traditional on-line electrocardiographic monitoring is
efficacious for arrhythmia detection done with QRS driven
algorithms. However, on line detection of ischemia is unreliable
and alternative methods, such as vectocardiography, are being
intensively tested. Vectocardiography requires very skilled
operators and it is not cost effective for widespread use. CVAT
compressed patterns facilitates ischemia detection by those
unskilled in electrocardiography, including patients, after a very
brief instruction period.
[0269] For on-line use of CVAT, the ECG signal is split and fed to
an oscilloscope and to the sound card of a computer (including palm
and lap tops). The signal is displayed in one CRT or LCD screen
with two windows. One window shows the real time ECG, another shows
the {fraction (1/64)} to {fraction (1/256)} (according to the heart
rate) visually compressed CVAT signal corresponding to the last 2
or more minutes. The CVAT visually compressed analog ECG clearly
shows ischemic patterns which in the real time display are likely
to go unnoticed because of their slow onset, observers lack of
electrocardiographic sophistication, visual fatigue etc.
[0270] CVAT's application to sleep apnea will now be described. A
small microphone is used to record respiratory sounds preferably
from the area surrounding the upper airway between the soft palate
and the larynx. The sound signal is fed into one channel of a
Holter recorder which is used to simultaneously monitor two ECG
leads (one right and one left precordial lead). Sound frequency
analysis is used to recognize normal breathing sound from snoring
and apneic spell induced by central or peripheral sleep apnea. The
simultaneously recorded electrocardiogram is used to monitor the
impact of sleep apnea in cardiac electrophysiology, and determine
the need for appropriate therapy. This apparatus and method can
replace costly in-hospital somnographic studies and provide a
cost-effective mean to diagnose and monitor sleep apnea patients at
home.
[0271] Experimental Results
[0272] A Comparison of the Results of Paired Analysis of Holter
Tapes Using a Conventional Algorithm and CVAT
[0273] Objective
[0274] The purpose of this study was to compare the relative
efficacy of two different computer-aided 24 hours Holter monitoring
analysis techniques to detect ischemia in 24 hours magnetic tape
Holter recordings.
[0275] An officer of the company which provided the Holter tapes
and a copy of the corresponding report, selected the tapes to be
analyzed. Initially, at the request of the CVAT inventors and
analyzer, tapes known to have signs of ischemia were selected.
Later in the study, random tapes were sent for CVAT analysis.
Hence, a selection bias was initially introduced, at the request of
the CVAT analyzer; such conscious bias should work against CVAT and
in favor of the algorithm method.
[0276] A total of 67 tapes were analyzed by both methods and the
findings are reported below. The Holter recorded analog signal, as
retrieved by the CVAT technology, is archived in compact discs to
avoid tape stretch and other artifacts, should reanalysis be
desired. The reports are identified by the five-digit number
assigned at the source of the Holter tapes followed by a capital
letter which identifies the compact disc in which the analog signal
is kept.
[0277] A state-of-the-art computer algorithm was compared to the
instant CVAT method for the retrieval, uploading and analysis of
the ECG signal encoded in the Holter magnetic tapes. All the
electrocardiographic signs detected with CVAT are classical for
ischemia as described in standard electrocardiography textbooks and
peer reviewed journals.
[0278] Results
[0279] The following table identifies the tapes which had:
4 No ischemia Ischemia found by both the algorithm and CVAT
Ischemia detected by the algorithm but not by CVAT and Ischemia
identified by CVAT but not by the algorithm ISCHEMIA ISCHEMIA FOUND
BY FOUND BY ISCHEMIA CVAT AND ALGORITHM FOUND BY NO ISCHEMIA
ALGORITHM ONLY CVAT ONLY N = 5 N = 12 N = 1 N = 49 87247 A 87250 A
87251 A 87138 A 87240 B 87246 B 87245 B 87133 B 87083 C 87015 C
87016 C 86952 C 87084 D 87115 D 87132 D 87143 D 87253 E 87321 E
87344 E 87331 F 87337 F 87339 F 87341 F 87325 G 87327 G 87340 G
87442 G 87438 H 87441 H 87443 H 87450 H ISCHEMIA ISCHEMIA FOUND BY
FOUND BY ISCHEMIA CVAT AND ALGORITHM FOUND BY NO ISCHEMIA ALGORITHM
ONLY CVAT ONLY 87356 J 87369 J 87371 J 87372 J 87376 K 87377 K
87378 K 87379 K 87380 L 87383 L 87385 L 87479 L 87490 M 87495 M
87497 M 87499 M 87480 N 87494 N 87498 N 87496 N 87500 O 87507 O
87513 O 87536 O 87510 P 87523 P 87525 P 87526 P 87527 Q 87528 Q
87529 Q 87533 Q 87535 R 87537 R 87538 R 87544 R Hence 62 of the 67
tapes analyzed had ischemic electrocardiographic signs. Of these
62, one (1.5%) was detected by the algorithm only, 12 (20%) by both
the algorithm and CVAT, 61 (98.4%) by CVAT and 49 (78.5%) by CVAT
only.
[0280] The following results deserve comment:
[0281] Holter No 87084 D
[0282] Was the only tape in which the algorithm found
electrocardiographic signs of ischemia and CVAT did not. This is a
single lead recording of less than optimum quality, the algorithm
found ST elevation in this single lead. CVAT did not find ST
elevation but J depression with biphasic and inverted T waves. To
keep the bias constant and against CVAT, this will not be
considered a false positive finding.
[0283] Holter Tapes in which Ischemia was Found by Both, the
Algorithm and CVAT
[0284] 87250 A
[0285] The algorithm found ST depression in the upper lead only
CVAT found ST depression in both leads
[0286] 87251 A
[0287] The algorithm found ST depression in the upper lead only
CVAT found ST depression in both leads
[0288] 87240 B
[0289] The algorithm found ST segment "sagging" in the upper lead
only CVAT found ST depression in the upper lead and elevation in
the lower lead
[0290] 87083 C
[0291] The algorithm found slight ST depression in the upper lead
CVAT found ST depression in the upper lead and elevation in the
lower lead
[0292] 87016C
[0293] The algorithm found ST depression in the upper lead CVAT
found ST depression in the upper lead and elevation in the lower
lead
[0294] 86952 C
[0295] The algorithm found ST depression in the upper lead CVAT
found ST depression in the upper lead and elevation in the lower
lead
[0296] 87441 H
[0297] The algorithm found ST depression in the upper lead only
CVAT found ST depression in the upper and lower lead with shifts to
ST elevation in the lower lead
[0298] 87356 J
[0299] The algorithm found ST depression in the upper lead only
CVAT found ST depression in the upper and lower leads
[0300] 87372 J
[0301] The algorithm found ST depression in the upper lead CVAT
found ST depression in the upper lead and elevation in the lower
lead
[0302] 87526 P
[0303] The algorithm found 2 minutes of ST depression in the upper
lead CVAT found constant ST depression in the upper lead with ST
depression shifting to elevation in the lower lead.
[0304] The algorithm and CVAT had concordant ST segment findings in
tapes No 87138 A and 87253 E only. In both instances, the ST
segment depression was in the upper lead only. In 10 out of 12
tapes the algorithm did not find ST shifts in the lower lead which
were detected by CVAT. The right precordial lead seems to be the
one recorded in the lower lead and frequently it is of lower
voltage (and hence dynamic range) than the upper lead. The lower
voltage probably renders the right precordial lead more susceptible
to greater obliteration of the signal by the under-sampling,
compression, smoothing and filtering used by the algorithm.
[0305] Conclusion
[0306] Of the 62 patients who had ischemic electrocardiographic
signs in the Holter tapes, 61 (98.4%) were detected by CVAT and 13
(20.9% including a probably false positive finding) by the
algorithm. This ratio is similar to previous experience comparing
algorithms versus visual analysis of the magnetic tape where eight
or nine out of ten patients known to have ischemia were missed by
different algorithms tested. In 10 of 12 instances of ischemia
detected by both methods, the algorithm failed to detect ischemic
signs in the right precordial lead. The high rate of ischemia found
in the total sample is not representative of the general population
but probably reflects pre-selection bias introduced by the
perceived need for Holter evaluation as part of a cardiovascular
work up. It is known that a common reason for arrhythmia is
myocardial ischemia, be it symptomatic or silent.
[0307] As explained in detail above, the instant invention uses
algorithms and software in a novel way for the analysis of
electric, magnetic and/or pressure waves of biological origin with
the purpose of facilitating the diagnosis of pathologic states in
human and veterinary medicine. The technique is applicable (but not
limited to) the analysis of signals encoded in the
electrocardiogram, electroencephalogram, myography, nerve
conduction, plethysmography and other respiratory functions, blood,
intracardiac, intracerebral and other vital fluid pressures.
[0308] As explained above, an actual reduction to practice has been
done using the algorithm encoded in the SOUND FORGE XP, VERSION 4.0
software, developed and marketed by SONIC FOUNDRY, a company
located at 754 Williamson St. Madison, Wis. 53703. Another program
used is the EASY CD CREATOR, DELUXE EDITION, developed and marketed
by Adaptac, Inc. 691 South Milpitas Blvd., Milpitas Calif. 95035.
The signal processed to test the instant invention was obtained
through Holter recordings of the ambulatory electrocardiogram.
[0309] In accordance with the invention, the analog signal from,
for example, a Holter recording, is digitized, not to subject the
digital file to analyzes through mathematical, algebraic, neural
network or any other type of algorithms, but to optimize the high
fidelity reproduction, reconstruction, compaction, etc. of the
signal to facilitate quick visual scanning of the dynamic
electrocardiogram. Improving the state of the art sensitivity and
specificity of the analysis while preserving cost effectiveness are
primary objects of the present invention.
[0310] The digital file is used to reconstruct a high fidelity
rendition of the originally recorded analog signal for visual
analysis using different rates of compression (compaction) of the
original wave form to facilitate visual searching for the classic
electrocardiogram signs of ischemia which have been described
heretofore mainly during studies of ischemia induced during
exercise tolerance testing and lately during percutaneous balloon
dilation of the coronary arteries.
[0311] In accordance with a preferred embodiment of the instant
invention, the signal is digitized at 44,1000 HZ/SEC versus 125
(commercial) and 500 HZ/SEC (Harvard) using 16 bits instead of the
conventional 12 bits. This feature enables at least one or more
orders of magnitude improvement in the measurement of wave
amplitude and duration. Off the shelf sound editing software is
preferably used to optimize the digital storage of the analog
signal to then do digitally enhanced, high fidelity reconstruction
of the analog signal. The digitized wave files are also suitable
for compression to facilitate their transport through different
media. The instant invention enables reconstruction and
optimization of signals originally recorded into the magnetic
tape.
[0312] The invention enables quick scanning and identification of
electrocardiographic abnormalities by using the following
techniques:
[0313] digital acquisition of the ECG analog signal from the Holter
tape at 44,100 (or higher) HZ/SEC;
[0314] digitize through 16 bits card or higher;
[0315] reproduction and optimization of the analog ECG signal using
a high fidelity music editing software program such as SOUND
FORGE;
[0316] Visual analysis of the reconstructed compacted analog ECG
signal is facilitated by the use of different rates of compression
and decompression as well as the proper colors to enhance the
contrast between the signal and the background. The particular
heart rate generally determines the optimal rate of compression
which preferably ranges between {fraction (1/32)} and {fraction
(1/256)}. Color further facilitates an accurate visual analysis
thereof. It has been found that the use of a red signal on a black
background provides the best contrast, but other colors, as well as
black and white, may be used;
[0317] normalization, signal smoothing, image contrast enhancement,
and gain increase available for example, in music editing program
such as SOUND FORGE, are also tools which can optionally be used
during analog signal preparation and reconstruction;
[0318] The invention has identified a number of compacted analog
signal patterns some of which are shown and described herein, which
point to discrete classic electrocardiographic abnormalities
including, but not limited to, all the classic signs of myocardial
ischemia described heretofore. All forms of electrical alternans
are readily identified using these patterns. Familiarity with these
patterns is crucial for the quick identification (at a fast
scanning rate) of abnormal states which can be done by individuals,
such as high school graduates with minimum training; and
[0319] electrocardiographic analysis is thus reduced to a pattern
recognition process accessible to all health care personnel and not
restricted to highly skilled, cardiology trained professionals;
[0320] In accordance with the instant invention, suitable hardware
and software can be used for direct digital acquisition of the
signal (to replace initial storage into magnetic tape) through long
periods (days).
[0321] It is noted that the inventor has determined that red
signals and black backgrounds provide the best contrast for viewing
most of the signals in accordance with the instant invention. The
instant inventor has found that visual analysis is easier when such
a color contrast is used. In fact, it has been determined that in
many instances black and red contrast provides optimal conditions
for the visual analysis.
[0322] It is also noted that the graphs herein are only exemplary
and that other patterns may be used in accordance with the instant
invention. The instant invention enables 24 hrs of recorded
heartbeats to be accurately analyzed visually in approximately 20
minutes or less, thereby making visual analysis cost effective
while also improving the detection of abnormalities.
[0323] While the preferred forms and embodiments of the instant
invention have been illustrated and described it will be apparent
to those of ordinary skill in the art that various changes and
modifications may be made without deviating from the inventive
concepts and true spirit of the invention as set forth above, and
it is intended by the appended claims to cover all such changes and
modification which come within the true scope of the invention.
* * * * *