United States Patent
`US 6,487,442 B1
`(10) Patent No.:
`(12)
`:
`Vv.
`Wood
`45) Date of Patent:
`Nov.
`26, 2002
`
`
`US006487442B1
`
`(54) DETECTION OF ABNORMAL AND
`INDUCTION OF NORMAL HEAT RATE
`VARIABILITY
`
`2/1999 Lanidoetal.
`5,873,369 A
`4/1999 Golosarskyetal.
`5,891,044 A
`FOREIGN PATENT DOCUMENTS
`
`(76)
`
`Inventor: Nicholas Wood, 16 Ensign Rd.,
`Rowayton, CT (US) 06853
`
`(*) Notice:
`
`Subject to any disclaimer, the term ofthis
`patent is extended or adjusted under 35
`US.C. 154(b) by 0 days.
`(21) Appl. No.: 09/559,653
`(22)
`Filed:
`Apr. 28, 2000
`
`SU
`SU
`SU
`WO
`WO
`wo
`
`1607808 Al
`11/1990
`1683679 Al
`10/1991
`1769894 Al
`10/1992
`8809146
`12/1988
`9406350
`3/1994
`9602185 Al
`2/1996
`OTHER PUBLICATIONS
`“The Functional Model Regulation Homeokinesis of Heart
`Rhythm;” Golosarsky B., research worker, Odessa Research
`(SL) Unt, C17 aecceccccccccsccscssccsssssssssessssssssssen A61B 5/0468_Institute of Medical Rehabilitation (1989).
`Malik, Farrell, Cripps, Camm, Heart Rate Variability in
`Relation to Prognosis After Myocardial Infarction: Selection
`of Optimal Processing Techniques. Eur Heart
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`1989;10:1060-1074.
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`(52) US. C1. cece cneeeneeecscteneseneenees 600/515; 600/519
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`600/516, 517, 518, 519
`
`(56)
`
`.
`References Cited
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`
`Primary Examiner—Scott M. Getzow
`(74) Attorney, Agent, or Firm—Stevens, Davis, Miller &
`Mosher, LLP
`
`(57)
`
`ABSTRACT
`
`An apparatus and method for predicting potentially fatal
`arrhythmias up to twenty four hours in advanceof the event
`by employing formulas indicating either too little or too
`muchheartrate variability. A numberof these formulas have
`both predetermined upper and lower limits, which if
`exceeded for a period of time are a predictor of a potentially
`fatal arrhythmia. When a patient’s ALARM condition is
`predicted, whether the patient is indoors or outdoors, con-
`scious or unconscious, a redundant protocol is utilized to
`relay that ALARM condition to a central monitoring station.
`The central monitoring station informsthe patient’s doctor,
`and then uses what ever meansare available to transport the
`patient to the nearest emergency room for treatment. An
`apparatus and method for pacing the heart in a natural way,
`once a potentially fatal arrhythmia has been predicted is also
`disclosed.
`
`42 Claims, 22 Drawing Sheets
`
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`US 6,487,442 B1
`
`Page 2
`
`OTHER PUBLICATIONS
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`Malik, Xia, Odemuyiwa, Staunton, Poloniecki, Camm,
`Influence of the Recognition Artefact
`in the Automatic
`Analysis of Long-term Electrocardiograms on Time—do-
`main Measurement of Heart Rate Variability, Med. Biol.
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`Malik, Camm, Components of Heart Rate Variability: What
`They Really Mean and What We Really Measure, Am. J.
`Cardiol. 1993; 72:821-822.
`Malik, Cripps, Farrell, Camm,. Prognostic Value of Heart
`Rate Variability After Myocardial Infarction: A Comparison
`of Different Data Processing Methods, Med. Biol. Eng.
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`Malik, Camm, Heart Rate Variability and Clinical Cardiol-
`ogy, Br. Heart J. 1994; 71:3-6.
`Malik, Camm. Significance of Long-term Components of
`Heart Rate Variability for the Further Prognosis After Acute
`Myocardial Infarction, Cardiovasc. Res. 1990;24:793-803.
`Fei, Malik, Short— and Long-term Assessmentof Heart Rate
`Variability for Postinfarction Risk Stratification, In: Malik,
`Camm, eds, Heart Rate Variability, Armonk, NY: Futura;
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`Heart Rate Variability Standards of Measurement, Physi-
`ological Interpretation, and Clinical Use, Circulation, vol.
`93, No. 5 (Mar. 1, 1996).
`Wood, N.B. “The Prediction of a Potentially Fatal Cardiac
`Event in the Next 2 to 24 Hours and the Prediction of a
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`Myocardial Infarction Related Death or Sudden Death”,
`Computers in Cardiology conference proceedings (Sep.
`24-26, 2001).
`Schmidt, Georg, et al “Heart—Rate Turbulence after Ven-
`tricular Premature Beats as a Predictor of Mortality After
`Acute Myocardial Infarction”, The Lancet, vol. 353, Issue
`9162, p. 1390(1), (Apr. 24, 1999).
`de Bruyne, Martine C., et al “Both Decreased and Increased
`Heart Rate Variability on the Standard 10-Second Electro-
`cardiogram Predict Cardiac Mortality in the Elderly: The
`Rotterdam Study”, American Journal of Epidemiology,vol.
`150, No. 12, pp. 1282-1288 (Dec. 15, 1999).
`Ziegler, D., et al “Normal Ranges and Reproducibility of
`Statistical, Geometric, Frequency Domain, and Non-Linear
`Measures of 24—Hour Heart Rate Variability”, Horm Metab
`Res Issue 12, pp. 672-679 (Dec. 31, 1999).
`Pinar, Eduardo, et al “Effects of Verapamil on Indexes of
`Heart Rate Variability After Acute Myocardial Infarction”,
`The American Journal of Cardiology, vol. 81, Issue 9, pp.
`1085-1089 (May 1, 1998).
`Deligiannis, Asterios, et al “Effects of Physical Training on
`Heart Rate Variability in Patients on Hemodialysis”, The
`American Journal of Cardiology, vol. 84,
`Issue 2, pp.
`197-202 (Jul. 15, 1999).
`
`Hayano, Junichiro et al “Prognostic Value of Heart Rate
`Variability During Long-Term Follow-Up in Chronic Hae-
`modialysis Patients with End-Stage Renal Disease”, Neph-
`rology Dialysis Transplantation, vol. 14,
`Issue 6, pp.
`1480-1488 (Jun. 1999).
`
`Lotze, Ulrich, et al “Cardiac Sympathetic Activity as Mea-
`sured
`by Myocardial
`123-I—Metaiodobenzylguanidine
`Uptake and Heart Rate Variability in Idiopathic Dilated
`Cardiomyopathy”, The American Journal of Cardiology,
`vol. 83, Issue 11, pp. 1548-1551 (Jun. 1, 1999).
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`Ho, Kalon K.L.et al “Predicting Survival in Heart Failure
`Case and Control Subjects by Use of Fully Automated
`Methods for Deriving Nonlinear and Conventional Indices
`of Heart Rate Dynamics” Circulation, vol. 96, pp. 842-848
`(1997).
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`Makikallio, Timo H., et al “Heart Rate Dynamics Before
`Spontaneous Onset of Ventricular Fibrillation in Patients
`with Healed Myocardial Infracts”, The American Journal of
`Cardiology, vol. 83, pp. 880-884 (Mar. 15, 1999).
`
`Reardon, M., et al “Changes in Heart Rate Variability With
`Age”, Pacing Clin. Electrophysiol., vol. 11., Part 2, pp.
`1863-1866 (Nov. 1996)(Abstract).
`
`Skinner, J.E., et al “New Non-Linear Algorithms for Analy-
`sis of Heart Rate Variability; Low Dimensional Chaos
`Predicts Lethal Arrhythmias”, Nonlinear Analysis of Physi-
`ological Data, Springer, pp. 129-166 (1998).
`
`Fauchier, Laurent et al. “Prognostic Value of Heart Rate
`Variability for Sudden Death and Major Arrhythmic Events
`in Patients with Idiopathic Dilated Cardiomyopathy”, Jour-
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`
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`U.S. Patent
`
`Nov.26, 2002
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`Sheet 1 of 22
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`Nov.26, 2002
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`U.S. Patent
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`U.S. Patent
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`U.S. Patent
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`Sheet 13 of 22
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`US 6,487,442 B1
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`Fig. 8
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`Sheet 14 of 22
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`US 6,487,442 B1
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`Fig. 9a
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`< From Fig. 9a
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`906
`908
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`Pulse Detected
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` <Yes
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`No>
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`To Fig. 9b >
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`910
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`>
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`>
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`921
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`21
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`No>
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`To Fig. 9b >
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`>
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`To Fig. 9b >
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`Sheet 15 of 22
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`Fig. 9b
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`901
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`Patient with
`Wrist Monitor
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`961
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`962
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`<On
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`Manual ALARM
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`Cancel>
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`302~
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`Monitor 1921
`on Wrist
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`
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`
`
`928
`No
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`Date & Time
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`901a
`<
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`< To Fig. 9a
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`From Fig. 9a
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`914
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`916
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`Dead or Dying
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`>
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`>
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`From Fig. 9a
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`>
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`To Fig. 9d
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`From Fig. 9d |
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`Sheet 16 of 22
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`Fig. 9c
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`THIS PAGE INTENTIONALLY LEFT BLANK
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`Sheet 17 of 22
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`US 6,487,442 B1
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`920
`<ACRR .
`
`RR Time Intervals
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`rom Fig. 9b
`920a
`
`
`
`
`Vv
`
`Fig. 9d
`
`$23
`ARR
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`>
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`
`From Fig. 9b
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`>
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`>
`
`Vv
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`925
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`+1.0i
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`KANNHeart Rate
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`929
`+1.0
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`(
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`To Fig. Of
`
`To Fig. 9f
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`{To Fig. 9f
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`Sheet 18 of 22
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`US 6,487,442 B1
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`Fig. 9e
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`<
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`<
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`<
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`<
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`From Fig. 9f
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`From Fig. 9f
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`< Conscious
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`<
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`
`Consciousness
`
`
`
`Unconscious
`
`>
`
`< Call MD
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`<
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`
`
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`Central
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`onitoring Station
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`Call Patient
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`>To Fig. 9f >
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`Cannot call MD nor Patient >To Fig. $f >
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`>
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`Patient's MD calls
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`Last Resort
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`>
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`>
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`>
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`>
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`>
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`>To Fig. 9f >
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`Sheet 19 of 22
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`Fig. Of
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`From Fig. 9d
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`Sum of + & - points
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`
`ommunication Syste
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`
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`
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`941
`945
`943Land To 9e
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`Cell Phone & Pager
`
`
`Central Monitoring suggests patient go to ER
`
`s72“Icentral Monitoring calls 911. Asks EMS transport patient to ER
`
`MD calls 911, and asks EMS to transport patient to ER
`
`Good Samaritan calls 911, and asks EMS to transport patient to ER Patient goes to the ER
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`Sheet 20 of 22
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`Fig. 10
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`Sheet 21 of 22
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`US 6,487,442 B1
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`2010
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`1921
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`2000
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`2020
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`2030
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`Fig. 11
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`Nov.26, 2002
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`G
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`f} Pay
`RA
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`1
`DETECTION OF ABNORMAL AND
`INDUCTION OF NORMAL HEAT RATE
`VARIABILITY
`
`BACKGROUND OF THE INVENTION
`
`1. Field of the Invention
`
`The normal heart rate is slightly irregular. Generally,
`normal irregularity of the heart rate reflects the permanent
`adaptation of the human body to the environment. In this
`context the first sign of an impaired heart rate is either a
`persistent increase or a persistent decrease in the variability
`of the heart’s rate. Sometimes the change in the heart rate
`alternates between increases and decreases in the variability
`of the heart’s rhythm, and vice versa. Prolonged increases,
`or decreases, and combinations thereof, can lead to cardiac
`adverse events ranging from non-sustained ventricular
`tachycardia to cardiac arrest.
`It is believed the variability of the heart rate is controlled
`by two branches of the autonomic nervous system;
`the
`sympathetic branch and the parasympathetic branch. The
`sympathetic branch increases the heart rate. Its prime func-
`tion is to prepare the body forstress, the so-called “fight or
`flight response.” The parasympathetic branch decreases the
`heart rate as when eating or sleeping.
`This invention relates to the detection of normal and
`
`abnormalheart rate variability and the induction of normal
`heart rate variability. More particularly, the invention relates
`to methods and apparatus for the detection of a patient’s
`heart rate variability that we believe is indicative of a
`patient’s sympathetic/parasympathetic stress balance,or dis-
`tress imbalance.
`
`The invention also relates to heart monitoring devices
`used by individuals monitored in hospital intensive care
`units; by patient’s after discharge from a hospital intensive
`care unit; and by patients when exercising to let them know
`that their stress state is optimal for conditioning their bodies.
`The invention further relates to control of a pacemaker or
`cardioverter defibrillator with a pacemaker so that when the
`patient’s heart rate is abnormal and distressful, according to
`the invention, a pacemakeror cardioverter defibrillator with
`a pacemaker induces a heart rate with a pseudo-normal or
`patient recorded variability for each particular patient.
`The invention still further relates to a pacemaker that
`induces pseudo-normal or patient recorded heart rate vari-
`ability.
`2. Background Description
`In the Soviet Union, Rhythmography, that is the study of
`normal and abnormal variations in the heart, was utilized
`extensively to determine the condition of individuals and
`their stress state. This was particularly true of cosmonauts.
`It was determined, for example, that the heart rate variability
`of a conditioned athlete is much greater than that of person
`with coronary disease. That is, the histogram of heart rate
`variation of a well conditioned athlete exhibits a broad range
`of variability in the Time Intervals between heart beats and
`a low relative Amplitude of the Mode. That is the highest
`number of Time Intervals recorded in a series of Time
`Intervals. The histogram of a person with a coronary disease
`exhibits a narrow range of variability and a high relative
`Amplitude of the Mode, that is the peak of the histogram.
`Boris Golosarsky, previously received two patents in the
`Soviet Union, namely SU-1683679 and SU-1769894.
`SU-1683679 is for an apparatus, which enables a physician
`to determine the arithmetic Mean, the Mode, the relative
`Amplitude of the Mode, and the range of variability of a
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
`
`2
`in the Soviet Union,
`In the second patent
`subject.
`SU-1769894, he disclosed how these measurements may be
`utilized together with electrosleep to treat post myocardial
`infarction e.g., heart attack patients.
`GW Scientific, Inc. measured a patient’s heart rate vari-
`ability in relation to the patient’s baseline heart variability
`using mathematical constructs such as UV, AMo, and DX,
`all as described in U.S. Pat. No. 5,718,235, incorporated
`herein by reference in its entirety.
`Polar Electro Oy of Finland has a patented apparatus
`comprised of a chest strap with a two lead ECGsignal sensor
`and transmitter, which transmits the heart beat Time Inter-
`vals to a wrist mounted unit that can be conveniently used
`in this invention. See U.S. Pat. Nos. 4,625,733; Des. 278,
`746; and Des. 287,403, all incorporated herein by reference
`in their entirety.
`Pulse sensors of various types may also be used to detect
`the Time Interval between heart beats, (Start-of-Systole to
`Start-of-Systole, SOS),
`is essentially equal
`to the Time
`Interval between RR peaks in an electrocardiogram, (ECG).
`Additional background information is disclosed by
`Baevsky, R. M., Kirillow, O. I., Kleckin, C. Z., (1984),
`Mathematical Analysis of Stress Changes in Heart Rhythm,
`Moscow, Academy of Science, USSR.
`Schmidt et al, “Heart-rate Turbulence After Ventricular
`Premature Beats As a Predictor of Mortality After Acute
`Myocardial Infarction,” Lancet Apr. 24, 1999; 353 (9162)
`:1390-6, relates to ACRRs.This article discloses a formula
`for predicting myocardial infarction 21 to 24 months in
`advance. In contrast, the present invention predicts up 24
`hours in advance. The formulain this article is quite different
`from those employed in the present invention.
`
`SUMMARYOF THE INVENTION
`
`Definitions
`
`TABLE A shows there are five abnormal predictive
`markers, which are comprised of two continuums, the Heart
`Rate Variability continuum andthe Heart Rate continuum,as
`well as Erratic Variability. The Heart Rate Variability con-
`tinuum has, as its extremes, high and low variability. The
`Heart Rate continuum has,as its extremes, bradycardia and
`tachycardia. Erratic Variability, is comprised of Premature
`Ventricular Contractions (PVCs) and Atrial Fibrillation
`(A-Fib). TABLEA lists the parameters in each continuum
`Values for these parameters are calculated by formulas and
`compared with values which are considered normal and
`values which are considered abnormal as explained in the
`specification. These parameters in TABLEA arealso labeled
`by reference numerals and these reference numerals may be
`employed elsewhere in the specification when discussing the
`parameters.
`
`TABLE A
`
`HEART RATE VARIABILITY CONTINUUM
`
`High Variability
`dispersion of heart beats
`Absolute SPS(1)
`Absolute AMo(3)
`Absolute DX(5)
`Absolute DX/Median(7)
`
`Normal
`
`Normal
`Normal
`Normal
`Normal
`
`Low Variability
`centrality of heart beats
`Absolute SPS(2)
`Absolute AMo(4)
`Absolute DX(6)
`Absolute DX/Median(8)
`Low HRV(9)
`2.0 Caution > 2.5
`ALARM(10)
`
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`3
`
`TABLE A-continued
`HEART RATE CONTINUUM
`
`bradycardia(11)
`
`tachycardia(12)
`Normal
`ERRATIC VARIABILITY
`
`ACRR(13)
`PVCs & A-Fib
`
`Data sources: ECG (RR) Time Intervals or pulse wave
`Start-of-Systole to Start-of-Systole (SOS) Time Intervals
`from the hardware sources discussed elsewhere. (Note: RR
`and SOSTimeIntervals are used interchangeably to indicate
`the Time Interval between heart beats. 60 seconds divided by
`the Time Interval in seconds equals beats per minute, bpm.)
`Time Interval: A Time Interval is the duration of time
`between heart beats, or RR peaks, preferably measured to an
`accuracy of 20 milliseconds, 0.02 seconds. The accuracy of
`the Time Interval can range from 15 milliseconds to 30
`milliseconds.
`
`is a series of Time
`Time Segment: A Time Segment
`Intervals, which can vary in length from 51 TimeIntervals
`to 301 TimeIntervals. The preferred default setting is 101
`Time Intervals. Typically, from this 101 Time Intervals, up
`to about 6 outliers are removed.
`
`The time between each heart beat is designated an RR
`Time Interval. RR Time Intervals are then dividedinto three
`subsets as shown in TABLE B.
`
`TABLE B
`
`RR Time Intervals (milliseconds
`
`NN
`
`ACRR
`
`MARR
`
`75 to 125
`
`1 to 74 and/or 126 to 169
`
`0 and/or 170+
`
`(Normal-to-Normal): Normal-to-Normal means a normal
`Time Interval between an RR peak. NN TimeIntervals are
`used to calculate twelve of the thirteen predictive markers.
`NN equals 75 to 125 milliseconds.
`ACRR (Abnormal Cardiac RR): Abnormal Cardiac RR
`means when the present Time Interval differs from the
`previous Timeinterval by +25% or -25%, andthis situation
`occurs 50 or more times while accumulating a Time Seg-
`ment of 101 NN Time Intervals, then this Time Segmentis
`an ACRR Time Segment. If this condition persists for 52
`minutes, or longer, then this is either a +2.5 or -2.5 point
`ALARM,asinfluenced by the results of “Absolute SPS”
`through “2.0 Caution>2.5 ALARM” formulas, the first 10
`formulas, for the parameters as set forth below. ACRRsare
`comprised of Premature Ventricular Contractions (PVCs),
`and Atrial Fibrillation (A-Fib). ACRRsequal intervals of 1
`to 74 milliseconds, and/or 126 to 169 milliseconds.
`MARR (Motion Activated RR): Motion Activated RR
`means some sort of motion influenced the Time Interval
`
`between the RR peaks. MARRs equal intervals of Zero
`and/or 170+ milliseconds.
`Outliers are typically the three shortest and the three
`longest Time Intervals in a 101 NN Time Interval, Time
`Segment, and are discarded after ACRRs are removed from
`the Time Segment, and before calculations are made of the
`other 12 predictive markers.
`Non-Stationarity: If the Median and the Modediffer from
`each other in a 101 Time Interval Time Segment by 20% or
`more, than this is a case of non-stationarity and the values
`generated are discarded and not included in any calculations.
`
`4
`The following 10 formulas are for parametersall related
`to heart rate variability, HRV. The ALARM trigger points
`and the number of Time Segments the ALARM condition is
`present are for patients 55 years and older.
`Absolute Sympathetic/Parasympathetic Stress
`(ABS.SPS): Sympathetic/Parasympathetic Stress is deter-
`mined by the formula:
`
`SPS=V(0.5/DX)°+(AMo/10)2
`
`In a Time Segment of 95 NN Time Intervals (101 NN
`TimeIntervals minus6 outliers), if SPS equals or exceeds 48
`for any 25 Time Segments out of 50 Time Segments, then
`this is a +2.5 point ALARM. In a Time Segment of 95 NN
`Time Intervals, if SPS is between 47 and 3.0, then this is
`normal condition.
`In a Time Segment of 95 NN Time
`Intervals, if SPS equals or is less than 2.5 for any 25 Time
`Segments out of 50 Time Segments, then this is a -2.5 point
`ALARM(Parameters 1 and 2 of TABLE A).
`Absolute AMo (ABS.AMo): Amplitude of the Mode is
`the largest number of identical Time Intervals occurring in
`the Modeof a Time Segment, (e.g. 70 for 70 Time Intervals
`out of 95 Time Intervals.)
`In a Time Segment of 95 NN TimeIntervals, if AMo, the
`most frequent heart rate, occurs 90 times or more for any 25
`Time Segments out of 50 is a 2.5 point ALARM. In a Time
`Segment of 95 NN TimeIntervals,if the average rate occurs
`between 11 through 94 times is Normal. In a Time Segment
`of 95 NN TimeIntervals, if AMo the most frequent heart rate
`occurs 10 times or less for any 25 Time Segments out of 50,
`then this is a -2.5 point ALARM. (Parameters 3 and 4 of
`TABLEA).
`Absolute DX (Delta X): Delta X is the difference between
`the longest value for a Time Interval in a Time Segment and
`the shortest value, after outliers, and ACRRs,if any, have
`been discarded (e.g. longest equals 0.72 secondsless short-
`est equals 0.64 seconds=0.08 seconds=Delta X).
`if the
`In a Time Segment of 95 NN Time Intervals,
`difference, DX, between the longest and the shortest heart
`rate is 0.06 secondsorless for any 25 Time Segments out of
`50 is a +2.5 ALARM. In a Time Segment of 95 NN Time
`Intervals,
`if the difference between the longest and the
`shortest heart rate is between 0.49 through 0.07 seconds is
`normal. In a Time Segment of 95 NN TimeIntervals, if the
`difference, DX, between the longest and the shortest Time
`Interval is 0.50 seconds or more for any 25 Time Segments
`out of 50, then this is a -2.5 ALARM. (Parameters 5 and 6
`of TABLEA).
`Median (M): The Median is the Time Interval in a Time
`Segment, in which there are equal number Time Intervals
`equal to or larger than, and equal to or smaller than the
`Median TimeInterval (e.g. the 47th Time Interval in a 95
`Time Interval Time Segment).
`Absolute DX/Median (ABS.DX/M): Delta X divided by
`the Median is a combination of the two markers above, DX
`and Median.
`if
`In a Time Segment of 95 NN Time Intervals,
`DX/Median equals or is less than 0.02 for any 25 Time
`Segments out of 50 is a +2.5 point ALARM. In a Time
`Segment of 95 NN TimeIntervals, if DX/Median is between
`0.025 and 0.420 is normal in a Time Segmentof 95 NN Time
`Intervals, if DX/Median equals or exceeds 0.425 for any 25
`Time Segments out of 50, thenthis is a -2.5 point ALARM.
`(Parameters 7 and 8 of TABLE A).
`Low Heart Rate Variability (Low-HRV): Low-HRVis a
`condition where 100 or more Time Segments, which have a
`maximum variation 0.62 seconds or lower, with no more
`
`10
`
`15
`
`20
`
`25
`
`30
`
`35
`
`40
`
`45
`
`50
`
`55
`
`60
`
`65
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`6
`The parameters calculated by the following formulas,“a”
`through “e” and “f”, can be substituted for AMo and/or DX.
`Typically for each of AMoand/or DX replaced, one or more
`of parameters “a” through “e” and “f’ are substituted.
`(a) Standard Deviation Average Normal
`to Normal,
`SDANN: SDANNis a measure of the dispersion around the
`mean of NN TimeIntervals in a five minute Time Segment,
`after ACRRs (Premature Ventricular Contractions and Atrial
`Fibrillation, if any) have been discarded, according to the
`formula. A value of 50 or lower in a SDANN Time Segment
`is a predictive marker of a serious cardiac condition.
`
`10
`
`SDANN=V(i3x)"—(axy
`
`5
`then this condition is a +2.5
`than two (2) exceptions,
`ALARM. Low-HRVis a predictive marker of low heart rate
`variability. (Parameter 9 of TABLEA).
`2.0 Caution>2.5 ALARM: If CAUTION or ALARM
`signals, for the above four conditions (SPS, AMo, DX, and
`DX/M),exist for 960 minutes with a gap (a lack of a Caution
`or an ALARM)of no more than 60 minutes, then the +2.0
`Caution (calculated as 4 times 0.5 CAUTION points)
`becomes a +2.5 ALARM. This parameter is a predictive
`marker of low heart
`rate variability.
`(Parameter 10 of
`TABLEA).
`Moreover, a baseline for SPS, AMo, and DX is estab-
`lished between the 10th and 500th Time Segment. Any
`deviation above 150% or below 50% of the baseline for
`more than 45 minutes triggers both a Caution and an
`ALARMof2.5 points for any one of the three formulas. The
`preferred baseline time is 24 hours. TABLE C summarizes
`the parameters for establishing a baseline.
`
`TABLE C
`
`Parameters for triggering a Caution/ALARMafter a baseline
`has been established
`
`SPS
`
`AMo
`
`DX
`
`start = 10 Time Segments
`
`end = 500 Time Segments
`
`15
`
`20
`
`25
`
`(b) Point Normal to Normal 50 milliseconds, PNN50:
`PNNSO is a measure of the concentration of Time Intervals
`at 50 milliseconds or lower during a five minute PNN50
`Time Segment. A value of 50 milliseconds or lower in a
`PNNS50 Time Segmentis a predictive marker of a serious
`cardiac condition.
`(c) Amplitude of the Median (AM): The Amplitude of the
`Median is the 47th Time Interval occurring in a Time
`Segment, e.g. if the 47th Time interval is 0.70 and occurs 21
`times, them AM equal 21.
`(d) Full Width at Half Maximum (FWHM) The Full
`Width at Half Maximum is a measure of the dispersion of
`start = 10 Time
`start= 10 Time
`Time Intervals. The value of Half Maximum is onehalf of
`Segments
`Segments
`end = 500 Time
`end = 500 Time
`(AMo) or (AM) and the Full Width is the length of a
`Segments
`Segments
`horizontal line (DX) across the vertical line a