CA2033433C - Autonomic neuropathy detection and method of analysis - Google Patents

Abstract

A non-invasive, programmable cardio-respiratory monitoring system for performingautomated automated nervous system function tests by monitoring and analyzing ERG
signals in relation to specific paced breathing and/or posture regimens, and immediately computing and disclosing the test results automatically upon completion of one or all of the tests. The accuracy of these tests, which are currently being performed manually and/or with multiple components, is greatly improved by the invention's capability to issue automated audio-visual instructions to the patient, to analyze any major peak of the QRS
complex for determining heart rate variation, to discriminate between normal and abnormal ERG signals, and to edit the automated test results to enhance the validity of the test results.

Description

203~33 FIELD OF THE INVENTION
In summary, this invention adopts the heart monitor of U.S. Patent 4,679,144 to Cox et al (commonly owned with the pre~ent inventlon~, and u.~es the medical teaching that patients with autonomic nervous system dysfunction ~uch as in diabetic~ do not exhibit certain normal correlations of heart rate and breathing which can be ascertained by thls greatly improved and highly reliable portable diagnostic device for noninvasively evsluating the functioning ststus of the autonomic nervous system.

BAC~GROUND OF THE INVENTION
The heart monitoring device described in U.S. Patent 4,679,144 to Cox et al is capable of performing continuous, real-time analyses of E~G information derived from the patlent whlch portend underlying cardiac complications resulting from occluded coronary arteries or dysfunctlonal heart muscle.
Due to its programmable capabillties, the heart monitoring device can further instruct the patient on the manner of ~L

~34~

cardlsc treatment based on its anslyses.
This lnvention, which lS used for the evaluation of autonomlc nervous system functlon, ~ncorporates the rea~-time heart monitorlng cspabilities described in the sbove patent but extends its capabilities to include the evaluat~on of cardiovascular responses to predetermined breathing andJor posture regimens. This invention also includes an automated method for externally regulating these regi~ens by means of audio-visual instructions in order to accurately correlate cardlovascular responses to speclfic stimuli such as respiration and/or posture.
This invention, for the ev~luation of ~utonomic nervous system function, incorporstes the portable, self-contained real-time digital heart monitoring device and lts capabilities of the Cox '144 patent, specifically its real-time digital ~onitoring, recording and storing capsbilities of electrocardiographlc signals, but extends its capabilities to include the evaluation of the cardiova-~cular responses to predetermined breathing and/or posture regimens.
The cardio-respiratory digital analyses, computations, audio-visual cues for accurately performing the breathing andJor posture regimens, data transfer ~nd data editing c~pabilitles are unique to this invention. The cardio-respiratory analy~es were not applicable snd are not capable of being performed by the Cox '144 invention because of the 2~334~3 dlfferent ob~ectives snd methodologles of each Lnventlon.
The comput~tlons referred to as ''autono~c nervous system ~ANS) test results'' as used ln the ~pecificatlon and clal~s herein, shall be understood to include the Expl.atory/Insplratory ~E/I) ratio, Standard De~iation (SD), Mean Circular Resultant (hCR), Coefficlent of Variation, Valsslva Index, Posture Index, snd/or any future invented calculation or combination thereof.
The E/I Ratio con~ists of calculatlng the time between successive heart bests during a predetermined breathing regimen consisting of p~ced breathing cycles of inspirations ~nd expirations. Each breathing cycle is comprised of one inspiratory period and one expiratory period for a predetermined length of time. The cslculation continues by identifying the maximum interbest time during the expiratory period in the cycle, the minimum interbeat time during the inspiratory period in the breathing cycle, and then correlating these times using an establi~hed formula to produce the E/I Ratio. This formula consists of summing the maximum interbeat times of all expiratory periods and dividing that totai by the sum of the ~inimum interbeat time~ of all in~piratory perlods. To increase the accuracy of the EJI Ratio, the invention has the capability of further analyzing the morphology of e~ch heartbeat to distinguish normal from abnormal beats. Abnorral beats, whether generated from the heart of the patient or any other source, cannot be "regulated'- by paced breath1ng cycles. Thus, the ~33k33 capabillty to detect these abnormal beats and ellminate them from analyses w~ll greatly increase the ac_uracy of the E/I
Ratlo .
It shall be understood that the term, "interbeat time', as used ln the specifications and claims here~n, is used interchangeably with the terms, "R-R interval", ''peak-to-peak interval", heart beat interval'- and/or "distance between selected polnt on one signal to the correspondlng point on the succeeding signal".
The Standard Deviation is determined by meAsuring and recording all of the interbeat times during a predetermined breathing regimen ~uch as twenty-five paced breathing cycles. Each breathing cycle consists of one insplration and one expiration for a predetermined length of time. The mean interbeat time of the predetermined breathing regimen is cslculated. All interbeat times are plotted in relation to this mean interbeat time to provide a statistical estimate, referred to as the ~tandard deviatlon, of the variability of heart rate during the predetermined bresthing regimen.
Since the Standard Deviation is linked to the number of observations (i.e. heart rate), gradual changes ln heart rate resulting from poorly paced breathing regimens, or accumulation of non-valid interbeat tlmes due to the inability to identify abnormal beat , will erroneou~ly ~nfluence the calculation of the Standard Deviation. Therefore, it is advantageous to 2~33~3 have the capablllty to accurately pace the breathlng and to distlngulsh between normal and abnormal beats to increase the accuracy of the ANS tests. Thls invention has the capability to increase the accuracy by lncorporating lts abnormal beat detection algorithms and provlding lts automated audlovisual instructions to the patlent.
The Coefficient of Variation result lS a derivative of the Standard Deviation computation described above, wherein the Standard ~evlation value is divided by the ~ean interbeat time calculated during the predetermined bre~thing regimen.
To compute the Mean Circular Resultant (MCR), the invention identifies the time of each heart beat, as represented by an EKG signal, relatlve to the time of the beginning o~ each breathing cycle which is comprised of one lnspiration and one expiration. An angular displacement (0-360 degrees) from the beglnning of the breath cycle is calculated for each cycle.
These angles are converted to vectors comprised of X and Y
components for all breath cycles comprising the predetermined breathing regimen. The average X and Y components of these vectors are computed to form an 'average vector". The MCR is the length of this vector. Any correlatior. between breathing and the number of heart beats will show up as a length that differs from zero. A perfectly random distribution of heart beats will generate a mean circular resultant at or close to zero. Although the MCR is tolerant of abnormal beats, this 2 0 ~

lnventlon has the capab1llty to contlnua__y dlfferentl~te normal from ~bnormal beats whlch wlll increase the accuracy of the other autonomic tests belng sl~ultaneously performed.
The Valsalva Index conslsts of c~lcul~tlns the tlme between succe~slve heart bests and then relating the maxlmum lnterval durlng the predetermined breathlng reglmen to the minlmum lnterval during a period of tlme following the predetermlned breathing regimen. At the present tl-e, the standard predetermined breathing regimen for perfor_ing the Valsalva test, also referred to a Valsalva maneuve-, conslsts of twenty- second period of forced expiration followed by 8 one minute "rest" period during whlch the patient breathes at his usual pace. To increase the accuracy, the :..vention has the capabllity to repeat the predetermined breath;ng regimens and to incorporate its abnormal beat detection algor:thms during this ANS test .
The Posture Index is derived from calculating R-R intervals durlng the last portion of a series of positicnal changes by the patlent. A predetermined regimen of posture changes are used to derive this Posture Index. At the present .lme, the standard posltional changes consist of lnstructing the patient via the dispiay means to stand for ten seconds, l_e down or three minutes, and then stand for one ~1nute. It :s during the last minute of standing in which the maximum nterbeat interval between the 25th and 35th beats is divlded by the minimum ~- 2033i~33 lnterbeat lnterval between the 11th and 15th beatS. The Posture Index, also referred to as the 30/15 Rat~o, is then computed.
This 30/15 Ratio was defined by Ewlng ln the references cited herein. For thls calculatlon, the predetermined breath~ng regimen is the patient's usual non-paced rate of inspirations and expirations. This invention increases its accuracy with respect to the prior art due to the incorporatlon of lts abnormal beat detection algorlthms and its automated audiovlsual instructions to the patient.
The term "predetermined physical regimen" shall be understood to include either the predetermined breathing regimen or the posture regimen defined above on which several other tests are based, and any other such future invented test adopted to be performed with the use of the inventlon.
It shall be under~tood that the term, ''predetermined breathing regimen" and/or "predetermined posture regimen" and the like, ac used in the speciicatlon and claims herein when describing the speciic method for esch ANS test, is perormed according to established methods in practice today.
However, it is conceivable that the predetermined breathing and/or posture regimens may change but the present invention would still be capable of ~orking.
The audio-visual cues emitted by the present invent~on are unique because they instruct the patient in performing the predetermined breathing and/or posture regimens which are 2~33433 crltlcal for the accurate assessment of autonoml_ nervous system functlon. Unlike the Cox 144 patent, the instructlons of thls present inventlon pertaln to performlng the test, whereas the Cox 144 lnstructlonal capabillties pertaln to lssuing o treatment modalities based on the analyses performed during the monltorlng and recording of the EKG signal.
The external data handling and edlting capabillties are new to this invention. The term, "externai data handllng mesns J as used in the specifications and clalms herein, shall be understood to include all such optical emitters, recelvers, and coupler~ used to transfer data to and from the apparatus to separate and/or remote data recelvlng devices. The external data handling means described herein is consldered state-of-the -art, but it is conceivable that the handling means will change and the lnvention will still work. With the inclusion of the external data handling means, the capa~llitles of the Cox '144 patent are expanded to provide editing of the recorded, analy~ed, and ~tored data. Any and/or all portions of the raw data can be reviewed, so that the data automatically selected by the invention by which it based lts ANS test results, can be reselected, or edited. The ANS test results can then be recalcu'ated based on the manually reselected data by the operator.
There is also a group of devices which are capable of monitoring and recording ~KG signals either on ~agnetic tape (see 2033~3 U.S. Pat. No. 3,~67,934 to Thornton) or in soild-state ~e~ory ~see U.S. Pat. No. ~,S?9,1~4 to ~ox et al), but nelther of these devices are capable of correlatlng specific EKG
ntervals wlth speclfic respiratory and/or posture reglmens.
The present invention relates to an instrument which non-lnvsslvely monitors EKG information in relationship to the respiratory cycle and/or postural changes, and more specifically lt relates to a programmable self-contained instrument with automated audlo~isual instructlons to assist the patient and medical personnel in performlng a series of ANS tests using predetermined breathing and/or posture regimens.
The computstions during the~e predetermined breathing regimens consisting of cycles of inspiration and expiration are automatically calculated, and provide a key index of measurement in determining the existence of underlying ~utonomic neuropathy which portends not only cardiac-related diabetic complications including myocardial infarction, but also other sutonomic neuropsthies effecting digestion, sexual function, pain perception, kidney function, eye slght, etc.
Most recently, the detection of autonomic neuropathy, as determined by measuring beat to beat changes in heart rste (R-R
intervals) has been shown to be useful in identifying patients at risk for sudden death and~or sleep apnes. The ir.stantaneous ANS
test results derived from this automated invention will be used by the physician to assess and manage his/her patients, 2~33~33 su.h as dlabetics w~th ~utono~lc neurop~thles and/or patlents d agnosed with, but not llmlted to, coronary ~rtery dlsease, or to assist the physlcian in ~he diagnosls o autonomic neuropathy resulting from undisgnosed underlying disorders such as diabetes or ~ny other autonomlc dysfunction or cardlovascular autonomlc dysfunctlon whlch predlsposes a patlent to sudden death. It can also be used by the patient alone, with no assistance, when the patient is interested in self-~onitoring the progression, or lack of progresslon, of autonomic neuropathy. Furthermore, any or all of the data used to compute the ANS test results can be revlewed and edited, if necessary, due to the invention'~ external dats handling ~eans. If the data that were automatically selected by the inventlon to compute lts ANS results were invalid, the operator of the apparatus can reselect and manually input different dsta for automatic recomputation of the ANS test results.

DISCUSSION ~F DIABETES
Diabetes mellitus is a chronlc disorder characterized by abnormalities in the metabolism of carbohydra~es, proteins and fats. There are approximately ten million dlagnosed diabetics :n the United States of America. Ten percent o_ known diabetics have Type I diabetes mellltus resulting ln immunological destructlon of pancreatic cells known ss bet~ cells whlch 8, e responsible for releasing insulin. Wlthout these beta cells, the 1~

2 a 3 3 ~ ~ 3 Type 1 dlabetLc does not produce suffLc~ent l-sulln and therefore must take dally lnjectlons of insulin. .he other ninety percent are Type II dlabetlcs or non-lr.sulln dependent.
The~e patlents are usually dlsgnosed sfter ~he age o thlrty;
however, the onset of Type II diabetes is inslduous ~nd may go undetected and untreated for many years. Once diagnosed, these patients are often not dependent on insulin for surviv~l but m~y be treated with either insulin or an oral hypoglycemic agent in conjunction with a proper diet and exerc~se regimen. The etiology of Type II diabetes mellitus remains unknown, although a number of genetlc and environmenta! factors appear responsible.
In addition to those patients descriDed above, another group of individuals have been descrlbed as having Impalred Glucose Tolerance <IGT), a borderl,r,e diabetic state.
It has been shown that 25% of these individulas with IGT
eventually develop diabetes meliitus. In total, there are approximstely fifty million people in the United States slone who have a form of diabetes mellitus or other glucose intolerances. Early detection of diabetes ~ellitus, regardless of its etiology (Type I, Type II, or IGT), ls the best means for preventing and/or controlling diabetic c_mplicstions which primarily result from yesrs of untreated or poorly treated dlabetes. Thus, eariy detection leads to _ar;y treatment, and the subsequert preventlon of complic~tions.

2fa~3~33 The dlabetic la susceptlble to a series of compllcatLon~ lncludlng both perlpheral and autonomlc neuropathles which resul' in ~orbidity and premature mortallty. The morbldlty and mortality of patlents wlth diabetes mellitus is usually related to the macrovascular and microvascular complications of the disease which include retlnopathy (retinal disease), nephropathy (kldr.ey disease), amputatlons secondary to perlpheral vascular dlsease (loss of toes), and myocardial infsrctions secondary to coronary artery disease. Myocardial infarctlon is the leading cause of death in diabetics w1th onset after the age of t.h;rty with the majority of these myocardial infarctions being silent. The absence of pain during a myocardial infarction ln the diabetic patient has been attributed to autonomlc neuropathy.
About 50 percent (or more than 35,000) of non-traumatic leg and foot amputations in the U.S. are the result of diabetes. Each year 5,000 diabetics lose their -~lght. Ten percent of all diabetics develop nephropathy, accounting for thirty percent of new cases of renal disease in the U.S. each year. These dlabetic compllcations, which include both peripheral and autonomic neuropathies, occur in some form ln e~ery diabetic and usually occur in concert wlth each other.
Experimental evidence suggests that diabetic neuropathy is the result ot an abnormal sccumulation in the nerve fibers of chemical substances cal!ed polyols, which produce segmental 2~433 demyellnat~on ( loss OI segments of the nerve ~over1ng), process that results prlmarlly from hyperglycemla, or excess glucose.
Cllnical perlpheral neuropathy lS charac'erl-ed by symptomc of sensory loss, parestheslas (abnormal skin sensations), gross and fine motor incoordination, and paln, and is thus usually percelved by the patlent. Perlpheral neuropathy is often assessed by asklng the patlent to describe his symptoms but may slso be assessed by nerve conduction tests. Symptoms of autonomic neuropathy, on the other hand, may be more insidious in onset and therefore less obvious to the diabetic. For example, bladder dysfunction, postural hypotension, gastric distention, sweating aberrations, and pupillary abnormalities may not even be noticed or may be ignored by the patient. De~pite the "silence" of autonomic neuropathies, they carry a greater morbidity than peripheral neuropathies.
The problem facing medical practitioners is that visual symptoms of these complicatlons are not revealed until a fairly advanced stage hss been reached. Furthermore, the diagnostic tests available for assesslng peripheral and autonomic function are e1ther 1) invasive, ~3 labor intensive, 3) insensitive, 43 difficult to interpret, 5~
cumbersome, and/or 6) expensive. As a result, despite the awareness of these autonomic neuropathies resuit:ng from ~ 2~3~33 abete~ and other causes, and potentlally a~fectlng S0 m~ on people in the U.S. alone, these compllcatlcns remaln undiagnosed and/or unmanaged for many years.
Although the above dlscusslon focused on diabetes and its damaging effects on the autonomlc nervous system, there are a number of other condltions which adversely affect the functioning of the autonomic nervous s-~stem lncluding alcoholism, Parkinsonism, sleep apnea, impotence, toxic reactions, connective tissue diseases such 25 multiple sclerosis or Shy-Drager Syndrome, and most recently discovered, the human immunodeficiency virus ~HIV). The association of autonomic neuropathy and these conditions has been described in the following articles: "Autonomlc Neuropathy in an Alcoholic Population, Postgraduate Medical Journal 1987, 63:1033-1036 "Sy~te~lc Sclerosi-~: Another Disease with Autonomic Dysfunctlon 198&, American Neurological Association, 421-422; 'Somatic and Autonomic Function in Progressive Autonomic Failure and Multiple System Atrophy 1987, American Neurological Association, 692-699;"Disorders of the Autonomic Nervous System; Part 1. Pathophysiology and Clinical Features 1987, Annals of Neuro'ogy, 21; 5:419-426;
''Autonomic Neuropathy in AIDS", Lancet, 1987, Aug 8:343-344;
''Autonomic Neuropathy and HIV Infection'', Lancet, 1987, Oct 17:915. The value of assessing ~eart rate varlability as a means to identify patients at risk for sudden death has ~een described - 2~3~ t~3 ln these ~rtlcles: Kleiger RE, Miller JP et al. "Decreased Heart Rate Vsrlability and Its Associatlon with Increased Mortallty After Acute Myocardl~l Infarctlon", Amerlcan Journal of Cardlology, 1987; 59: ~56-262; Martln GJ, Magld Nh et al. ''Heart Rate Variability and Sudden De~th Secondary to Coron~ry Artery Disease Durlng Ambulatory Electrocardiographic Monitoring", American Journ~l of Cardiology, 1987 60: 8~-89; Bigger JT.
Klelger RF et al. "Component-~ of Heart Rate Varlabiltly heasured During Healing of Acute Myocardial Infarction'', American Journal of Cardiology, 1988; 61: 208-215; Rothschild ff, Rothschlld A, and Pfelfer M. ''Temporary Decrease in Cardiac Parasympathetic Tone After Acute Myocardial Infarction'', American Journal of Cardiology, 1988;62: 627-639.
Despite the increasing body of literature regsrding autonomic neuropathy resulting from conditlons other than dlabetes, mo~t of the information to date pertalning to the assessment and diagnosis of autono~ic nervous system function by means of evsluating heart rate, or R-R, variability during predetermined breathing andJor posture regimens has been derived from the disbetic population.
However, there have been several recent studies which have focused on the value of assessing heart r~te variability in patients with or without diabetes as a means to ~etect patients at risk for sudden death due to changes in autonomic tone. Such detection wil1 then be used for appropr1ate stratification of ~3 1~`~

patLents to addltlonal diagnostlc tests ~nd/or therapeutic maneuvers. Thus, the range of values for the E~I Ratio, Standsrd Devlatlon, Mean ~ircular Resultant, Vslsalva Index Posture Index and Coefflecient of Variatlon, w~lch are lndlcative of an abnormal or borderline functioning of the autonomic nervous system, has been b~sed on extensive studies of diabetlc pstients. However, the range of values may change depending upon the results of ongoing research, but the present invention would still be capable of worklng. Therefore, untii definltve studies are completed ~or each specific subset of p~tients belng evaluated by the present inventlon, the values lncorporated into the present invention may be used to diagnose autonomic dysfunction resulting from any condition. "~ormal' values have been derived from patients with no known disease states.

DISCUSSION OF THE PRIOR ART
Concern for patients with peripheral and autonomic neuropathy has led to the development of some devices for the assessment and diagnosis of these conditions. However, these prior art devices have the limiting factors previously discussed;
these limltation~ are not present ln this invention.
As for peripheral neuropathy testing, theze are a number o~
nerve conduction tests cur~-ently in use today. These tests are performed by ~pplying a small shcck to the nerves, for example, between the knee and the ankle. The voltage is 2 ~

then recorded wlth electron~c ampliflers fro~ a disk pasted to the skin overlying the indivldual musc!e kelng tested. In neuropathy, the speed of the lmpulse along the nerve lS
decreased, indicatlng ~n abnormallty. This test lS labor lntensive and lS only capable of evaluating one portion of peripheral nerve at a time. The results are not indicative of generalized perlpheral neuropathy or autonomlc neuropathy.
Another type of peripheral neuropathy test is needle electromyography whereby a needle is lnserted lnto several muscles and the electrical discharges are recorded.
While this test may evaluate peripheral nerves, it lS
lnvasive, expensive, and often not tolerated by the patient because it is extremely painful.
These are the only currently availaDle methods of objectively evaluatlng peripheral neuropathy. Typically, and most frequently, peripheral neuropathy lS evaluated by a physician during a phys~cal exam whereby the physician will test one's reflexes and one's ability to feel different kinds of sensations at various places on the skin using a reflex hammer and pointed object such as a pin. The results are based on the patient's perception of pain, and the physician's quantitative assessment of the patient's reflex movements.
Since these tests are not quantitative, lt is therefore dl~ficult to accur~tely evaluate the progression, or lack of progression, of peripheral neuropathy from one office Vislt to ~33~;~3 the next.
Furthermore, these te~ts are not applicabie to autonomlc nerve testing since autonom~c funct1on lS nelther lsOlat2d to a specif lC nerve nor are the affected nerves or organs locsted in accesslble areas. The autonomlc nervous system, also known as the involuntary nervous system, provides innervatlon to the heart, blood vessels, glands, and other vlsceral organs and smooth muscles. Hence, the autonomic nervous system is widely distributed throughout the body.
For autonomic neuropathy testing, which consists of evaluating both sympathetic and parasympathetic activity, one oi the easiest organs to test for autonomic dysfunction is the heart. The measurement of heart rate variation (R-R testing) during paced cycles of respiration has been well documented as a means to specifically assess the parasympathetic branch of the autonomic nervous system. One system for evaluating heart rate variability has been described by Rothschlld et al in a paper published in Diabetes Care, Vol. 10, No. 6, November-December 1987 entitled "Sensitivlty of R-R Variation and Valsalva Ratio in Assessment of Cardiovascular Diabetic Autonomic Neuropathy-. This system consisted of several separate components including an oscllloscope, EKG machine, and a stop watch. The patients had to be instructed by a trained individual during the entire test on the proper breathing regimens to be performed. Analysis of the results were then ~ ~ 3 ~ ~ 3 performed retrospectlvely on ~ somputer wlth lntervention by a skllled indi~ldual. Another system for recordlng, analyzlng, and correlating ~-R lnterval wlth resplratlon is described in Diabete~ Care, Vol. 7, No. S, ~eptember-October 1984 entllted "R-R Interval Studies: A Simple Office Protocol for Evaluation of Cardlac Autonomic Neuropathy-'. Thls system also consisted of several components includins an EKG machine and a stopwatch.
As described, a series of manual steps had to be performed and synchronized at specific tl~es during the respiratory cycles. These particular conigurations of equipment for R-R
testing require multiple components and skilled indlviduals for instructing the patient and analyzing the results, thus producing costly, labor-intensive, and cumbersome systems.
Furthermore, in order to obtain accurate results, the test methodology must be precise; that is, respiratory cycles must be paced regularly and the R-R lntervals must be precisely correlated with the respiratory cycles so that the analyses reflect an accurate assessment of the autono~ic nervous system.
Additionally, it is critically lmportant to distinguish between normal and abnormal beats because abnormal beats occur at irregular intervals and can not be "regulated'' by paced resplration. Thus, inaccurate detection of beats can greatly skew the results with the exception of Mean Circular Resultant which is a computation that is tolerant of abnorma;
beats included in the analysis. Consequently, the beat 2~33~3~

detectlon capabllltles descrlbed in the Cox '14~ patent are advantageous for lncress~ng the accuracy when calculating the E/I, Standard Deviatlon, Coefflcient of Varstlon, Valsalva Ratio, and Posture Indices.
The accuracy of the above described prlor art lS further compromised when an individual attempts to manually conduct these tests because of the simultaneous tasks whlch must be performed includlng instructing the patient on precise breathing and/or posture regimens whiie looking at a stopwatch, recordin~ the EK~ m~nually, and counting the number of required resplratory cycles and/or postural changes.
To evaluate the sympathetic branch of the autonomic nervous system, the Valsalva maneuver has proven to be a useful method. A system to perform the Valsalva maneuver has also been de-cribed by Rothschild in the article prevlously cited. This system also conslsts of several components as well as retrospective analysis of the results and the lack of automated instructions.
More specifically, to perform the Valsalva test, which includes forced expiration against against a resistance, the patient is instructed by a technician or physician to blow through the mouthpiece attached to a manometer so that the forced exhalation is sustalned for twenty seconds at a pressure of 40mm of mercury. The patlent 1~ then instructed to breathe normally for one minute before repeating the above 2 ~ 3 descrlbed V~isalva maneuver. Dur~ng each phase of the maneuver, forced exhalat~on followed by relaxed breathlng, the p~tlent lS
contlnually monitored wlth an EKG machine. One system for evaluating heart rate varlablllty durlng the Valsalva ~aneuver is descrlbed by Rothschild cited above. This system conslsted of recording the EKG slgnal onto magnetic tape for further off-line analysls by a computer. The heart rate variation was determlned by a vector-analysis technique to calculate the maxlmal heart rate interval, expressed as milliseconds, divlded by the minimal heart rate interval. The present invention provides for an automated method for performing the Valsalva test. With the use of audiovisual cues, the apparatus instructs the patient on the predetermined breathing regimens recommended for the Valsalva test while being monitored electrocardiographically by a sensing means attached to the patient and connected to the apparatus. The sensing means consists of the state-of-the-art electrodes disclosed in U.S. patent "14~ but it is conceivable in the future that sensing means will change and the invention will work. Thus, the term, 'sensing means", as used in the specifications and claims here~n shall be understood to include all such electrodes, ultrssound and the like devices. This ANS test result, referred to as the Valsalva Index, is computed by calculatlng the time between successive normal beats only, and then relating the maximum heart rate interval during the forced 2 ~ 3 3 .

explratory perlod of the predeterm1ned breath~ng reglmen to the mlnlmum heart beat lnterval durlng the perlod of tlme of relaxed breathing following the forced explratory perlod. The test result is instantaneous and automatic.
An sddltional test performed by a system described by Ewing ln an srticle previously cited to evaluate the parasympathetic branch o the autonomic nervous ~ystem is the posture test. To perform this test, the patient lies quletly on a couch and is then instructed by a technician to stand up for a minimum of thirty heart beats. Throughout the test, the patient is monitored electrocardiographically. The Posture Index lS derived retrospectively either by manually measuring R-R intervals or by analyzing the ECG data on an off-line computer. The present invention provides for an automated method and apparatus for performing the posture test. With the use of audiovisual cues, the invention apparatus instructs the patient on the predetermined posture regimens recommended for the posture test while being monitored electrocardiographically by a sensing means attached to the patient and connected to the apparatus. The derived ANS test result, referred to as the Posture Index, andfor 30/15 Ratio, is automatically and instantaneously calculated upon conclusion of the posture test by the invention device.

SUMMARY OF THE INVENTION
In summsry, starting from this posture technology, the ~0'334~

in~entlon goes forw~rd to prc~de ~ portable, automated, progr3mmabie, self-conta-ned heert mon~torLng devlce whlch ~n real-tlme on-golng manner iooks ~t each and every heart beat as lt relates to speclf lC predetermlned breathlng and/cr posture reg1mens. It ~urther lnstructs the pstient durlng each ANS test as to the proper breathing and~or posture reglmen to be performed using automated audlovlsual cues.
Because of the data analysls and storage abllitles and the speed and conflguratlon of current computer technology which are used ln the invention, the inventlon gives the pat~ent the benefit of undergoing several tests slmultaneously for assessing autonomic nervous system function;ng which would usually not be offered due to the inherent difficulties and expense wlth the currently avallable systems. Thus, the invention is a dramatic step forward in performlng automated autonomic nervous system testing using predetermlned paced breathing and/or posture regimens, and instantaneously computing, disclosing, and editing the ANS test results. Thus, the early diagnosis and management of autonomic nervous system dysunction resulting from diabetes and other diseases is facilitatec by the automated test methods of this invention.
Further, the me'hod and apparatus of the inventlon provide a gamut of tests so that both the sympathetic and psr~sympathetlc branches of the autonomic nervous --ystem can be evaluated, provide the abii;ty to calculate hear' rate 203:343~

varlstlvn by detectlng any ma~or peak of ~he ~RS complex not ~ust the R-wave; provlde the abllity to dlscrlmlnate between normal ~nd abnormal beats which wlll lncrease the accuracy of the tests; provide the ablllty to program the monitor to perform one or all of the autonomlc nervous system tests;
provlde the capabllity to lmmedlately review the test results for verlflcation of the apparatus selectlon of d-~a used for calculatlon of the ANS test results and prov~de ~ha capabllity to manually select other data for immed~te recalculstion of the ANS test result.
The above and other advantages of the lnvention will becGme cle~r rom the following detailed description when read ln conjunction with the accompanying drawlngs also form;ng part of this disclosure in which:

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows an EKG trace for a heart beat from a healthy person and the conventlonal names of the parts of the wavefor~;

Figure la shows two other EKG traces which could be taken fros.
different unhealthy persons or which may occur in healthy persons depend1ng upon the placement of the sensing means ~n the chest ;

2~33~

Flgure 2 l5 an over~l_ block ~agram ,. the hardware components compr1slng the app~r2tus of the ln~er.tlon.

F19Ure 3 lS an overall block dlagram deplctlng ~.~e software logic controlllng the dlfferent functlons of the invention.

Figure 4 i5 a schematlc o the loglc t,~2t controls the perfor~ance of any of the autonomlc nervous sys~em tests.

Figure 5 describes speclf;cally the Deat detec~on algorithm of Block 3040-2 whlch is enabled at the start of any autonomic nervous system test.

Figures 6 and 7 show the system logic ssr analyzing and categorizing the type of abnormal beats that 2-e judged to be representative of EKG ~ignals generated fro~ ~he heart of the patient.

Figure 8 shows the procedure for calculating the Explratory/Inspiratory Ratio and Mean Circular Resultant at the completlon of an error-free autonomlc nervous system test.

Figure 5 shows the procedure for calcula'lng the Standard Devlat-on and Coefficient of Varlation at the completion of an error-free autonomic nervous system test.

-- 2 ~ 3 ~ 3 Flgure 1~ shows the procedure for computlng the ~Jalsalva Index at the completlon of an autonomlc nervous system test.

Figure 11 shows the procedure for calculatlng the Posture Index.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to the drawings in more detail, Flg.
depicts a typical ECG waveform of the heart of a normal, healthy person whlch lncludes two heart beats, each of which includes a P wave of positive polarity, a ~RS complex consisting of a negatlve Q wave, a positive R wave, a negatlve S wave, and finally a T wave separated from the ~RS complex hy an ST
segment. J lS a point in the ST segment and defines the end of the S portion thereof.
Figure lA illustrates other ECG waveforms which dlffer from the "typlcal" ECG complex. These morphologies may result from underlying pathology of the myocardium ~heart muscle) or from monitoring the heart from different areas on the chest.
As shown, not all ECG waveforms may consist of ?-Q-R-S-~waves. Therefore, other intervals besides R-R may be used to calculate distances between successive beats. These lntervals may include ~S-~S, S-~, etc... as shown in Flgure lA.
Normally, in a healthy person with an lntact autonomic ~-- 2 ~

nervous system, tne E~G s.gnals wlll $iuctuate w~th the resp~ratory cycle. ~pec~f_cally, the heart r~te wlll ~ncrease dur~ng lnsp;ratlon and decrease dur~ng exp.ratlon. In other words, the ~-~ d~stances ~re messured, ~nd t~ese d~stances are then expressed as m~lllseconds or beats per m1nute, or more commonly referred to as heart rate.
Measurements can also be made between ~-~, as-~s, or any other correspond~ng points on succeed~ng EKG slgnals. In normal subjects, these heart beat intervals are shortened durlng inspir~tlon and proionged durlng expiration. In people whose autonomic nervous system has been damaged or is dys~unctional, these heart beat intervals remain constant or nearly constant throughout both phases of the respiratory cycle--inspirat~on and explration. This fact, the failure of these ~ntervals to respona normally in response to respiration has been documented as a cl~n~cal manifestation of underly~ng autonomic nervous system dysfunction resulting fro~ a number of systemic diseases such as diabetes mellitus, parkinson~sm, chronic k~dney failure, alcoholism, toxic or pharmacologic agents, or numerous neuropath~c diseases. Heart rate variat~on ~n response to resp~ration is well recogni~ed as reported by Wheeler and Watkins in the ~r~tish hedlcal Journa;, 1973, ~n a paper ent~tled, ''Card~ac Denervat~on in Diabetes''.
Heart r~te variat cn is pa-ticularly pronounced during deep breathing at a frequency of six breaths per minute.

-- 2Q331~3 ~or.versely, heart rate ~arlatlon lS gre~t,v ~imlnlshea or sbsent ln people such as dlabetlcs who have had damase to thelr vagus nerve w~lch lntrlnslcaily contr,is heart r2te ln response to stimuli such as breath,ng.
Referring now to Flgure 2, thls diagram is being incorporated ln lts entlrety wlth an addltlonai external data handling means by reference to U.S. ?atent No. 4,679,144 tc Cox et al wherein the present inventlon .3 co-owned by the inventors of the aforementioned patented lnventlon.
In Flgure 2, ' there is shown a generalized schematic view of the apparatus of the present inventlon in whlch leads 102, 103, and 104 represent electrodes and wlres attached to the patient P at predetermlned locations preferably in a conventlonal manner (the preferred embodiment envislons non-intrusive electrode-to-patient sensing means). The sensing means are preferably of the type of electrodes disclosed ln U.S. Pat. Nos.

3,420,223, 3,490,440, and 3,665,064. Lead 104 functions to ground the apparatu~, whlle leads 102 and 103 feed EKG slgnals, detected by the electrodes, to a pr~-amplifier and filtering component 10~ to perform two functlons: First, to amplify the signals detected by the electrodes, and second to ellminate undesirable no;se. The ampllfler, while of conventional design, must provide a uniform bandwldth to effectlvely amplify all of the co~ponents ln the E~G s;gnal wlthout produclng any distcrtions sc that the output slgnal 2&

~3~4:~3 from the ampllfler lS a true and ~mpl~f,ed reprcduct~on o~ tne EKG slgnal plcked up by the electrodes'-.
' The output of the ampllf_er lS fed to a converter 108 of the ~nalog-to-dlgital <A~D) type. The converter is connected, v,a a system bus lS~, to a mlcroprocessor 120 drlven by a clock 122 through connection 124, one or more random access memory (RAM) components 130, one or more read only memory (ROM) components '4~, an alpha-numerlc display dev~ce 145, a keyboard 1~5, an alarm means 175, and an optical emltter 185 with an optlcal interface to couple emltter 185 to system bus 150. A lithium battery (not shown) can be employed as a back-up for the memory components. A
keyboard lnterface component 160 couples keyboard 165 to the system bus 150, and an 1nterface ;70 couples alarm means 175 to the system bus lS0.'' The alarm means 175 msy consist of a beeper or other alarm means. The output from the optlcal interface 180 is sent to an optical coupler 185 which is not sltuated on the apparatus as indicated by the dotted line 186. Information can be either received from or emltted to the interface module 190 la the optical coupler 185. The lnformat~on is then stored in the interface module 190 for ~medlate or future output to an external data handling means 195 whlch may ~onsist of a modem, printer, or computer, or other ex~ernal data handling means. The speeds, capscitles, etc. of the hardware components needed to implement the invention can be determined by persons skllled in 203~33 these ar~ 5, basea on the teachlngs hereln.
Referring to Flgure 3, there lS sh-wn a genera;l~ed schematlc vlew of the program flow. When the lnventlon 15 turned on, ~10CK 3000 ~owers up the mlcroprOCessGr whlch ln turn perorms a series of checks to make certaln th~t the inventlon l5 functionlng properly. This serles of checks lnciudes initiallzlng all hardware elements to the proper conflguration for system operatlon and testlng the Random Access Memory (RAM) to ~nsure that data can be stored and retrieved prcperly. When the system is ready, a Main henu 3010 is displ~yed whlch provldes a startlng point from which the operator may access a desired function. If the operator is not familiar with the dlrect access keys to each of the different functions, Key "O" provides a HELP menu 3~12 which lists the functions and their corresponding access keys.
If Program Options 3016 is selected from the haln Menu, the program advances to Block 3018 whereby operator is prompted to select 1) one or all of the autonomic nervous system tests to be performed, 2) the format of the printed test results, ar.d 3) the audible alarm setting that assists the patient in pacing the respiratory cycles during the paced breathlng regimens. If the TONE is programmed "ON , a tone ~iil rise in pitch for inhalation and fali in pitch for exhalatlon durlng the performlng of any predetermined breathing regimen as a ~eans to pace the person's breathing regimens. ~he dlsplay 1~5 aiso paces the person's breathing regimens by means of a moving bar which ~ 2~3~:33 lengthens for lnnai~tlon and decreases ln lengt.. ~o- exhalatlon.
As a selectlon lS ~sde for an optlon, the pro ~am advances to the next optlon untll all selectlons h~ve be~n made. I~ no selectlon has been made, the display wlll read NO ~PTION SET-, and the program wlll remaln at Block 3018 unt.l at least one selectlon is made. The selections are then stored ln Block 3020, and the program loglc returns to the Main Menu 3010. Once the program options have been selected, the operator selects the clock function by pressing Key 5 on the Main Me~.u JC10. The clock function is accessed, and the time and date ere dlsplayed for review. To set the correct time and date in ~lock 3036, the operator presses the approprlate keys on the keyboard 165. Once the clock is set, the Real Tlme Clock 122 lS checked ~0~8. If the clock has not been set, the program returns to Set ~lock 3G36 and prompts the operator to reset the clock. Once the clock is set and the program verlfles that a valld time and date have been entered, the program returns to the Main Menu 3310.
Prior to performing an autonomic nervous system test, the operator erases any current tests stored in RAn by accessing the Erase option 3022 wlth Key 3 on the Main ffenu. The program checks to see if there are storea test data and var~aoies in Block 302~
and proceeds to clear the Random Access Memory (RAM) if prompted by the operstor to do so by pressing a verlfic2tion key on the keyboard. The prog-am returns to the Main Menu 3010.
When Key 6 ;s selected from the ffaln .MenL 3010, the RUN TEST

2033~3~

?rocedure lS ~ccessed, 3nd the program advances to ~hec~ ~ettlngs 3~4' where two checks a.e made. The flrst c~eck lS made on aut_nomlc nervous syste~ ~ANSj test program settlngs ln Block 3C--O. At least one ANS test re~ultlng ln one of the following test results -- E/I Index, Mean ~ircular Resultant, Standard Deviation, Valsaiva, or Posture, must have been chosen.
If no tests have been chosen, the display 145 s changed to read "N3 OPTIONS SET" and the program returns to the Main Menu 3010.
A second check ls made to see if test data snd varlables hsve been erased. If they have not been erased, the progra~ will prompt the operator with a message, "DATA NOT ERASED'', and the program loops until any key lS pressed. At key entry the progra~
returns to the Main Menu J010.
If at least one of the program options was selected in Block 3018, and if all current tests were erased in Block 3024, the program advances to the Test Menu 3044 which will display the programmed test options. ~he operator may choose to perfor~ the ANS tests in any order by ~electing the key corresponà~ng to elther the E/I test 3046, ~alsalva 3048, or Posture 304g.
The EJI test 3046 Wl.- ~e considered flrst. Specif1cally, when the E/I test is selected , the program aavances to Run Test 3G40. Prevlously selected test options are checked and test p~-ameters are set. A perlod of predeter~ined breathing reglmens, lasting for at least one ~1nute, follows ln whlch the pat-ent is abie to practice the preaetermined breathing regimen, gu.ded by 2~3'133 ~he d1splay 1~ and a tone 175 ~15 a~t1vated prlor to the start o~ the actu~l test). The EKG s1gnai lS checked to 1nsure sufslclent quallty for the test. The EKG s1gnai checklng loglc, also reserred to as beat detect1on, lS deSCrl~ed ln detall ln Flgure S. After s1xty seconds, the program prompts the patient to begln the 'est when convenient by means of a vlsual cue on the d1splay 145.
The ~'aisalva test 3048 operates slmllarly. After select~ng th1s opt1on, the ~un Test portion 3040 lS accessed wh1ch in~tlates an EKG signal check and provides a practlce period for the patient whereln the patient may practlce the predetermined breath1ng regimen consisting of forced exhalation and non-paced breathing. If the EKG signal is acceptable, the program prompts the patient with a vlsual cue to begin the test by exhaling sorcefully for twenty seconds at a metered rate. After the forced exhalatlon, there lS a recovery period consisting of a slxty-second period of non-paced relaxed breathlng dur1ng which time the patient's heart rate contlnues to be monitored electrocardigraphlcally. At the concluslon of the recovery perlod, the program provides an audiovlsusl cue to indicate the ena o~ the test.
The Posture test 3049 is also similarly performed although the Run Test 3040 parsmeters lnclude a predetermined posture reglmen ~nd a predetermined breathlng regimen comprised o~ only non-paced relsxed breathing. Foliowing a sixty-second period of 2~3~433 EKG sLgnal check~ng, the patlent lS prompted .su~liy to stand for apprGxlmate'y ~en seconds, lle down ~or three minutes, and then stand sgaln ~or slxty seconds. The patient ~s prompted wlth an audiovlsual cue when the test 1S completed.
At the completion of each ANS test, the program checks for ~ny errors 3050 that may preclude the caiculation o, the ANS test result. Such errcrs lnclude insufficlent or excesslve number of EKG signals detected during the runnlng o~ any test. Slnce all ANS test results are based on R-R intervals occurring at speclfic times during the predetermined breathing reglmens, the program verlfies that the necessary R-R intervals have ~een obtalned. If errors are present, the program prompts the person by dispiaying the error message such as "RATE TOO SLOW", ''RATE TOO FAST", or ''SIGNAL TOO WEAK'' ln Block 3052 before returning to the Maln Menu upon any key hlt. If no errors are present, the program advances to calculating and storing the ANS test results ~054 before returning to the Main Menu 3010. ~he calculations are described in more detail in Figures 8 and 9. The ANS test results are stored in RAM 130 until erased.
After the results are calculated and stored, the operator may transmlt the ANS test results to an external data display means by press;ng Key 2 on the Main henu. When selected, the prosram checks for the storage of at least one ANS test -esult ;n ~lock 3~54. I~ no results are storea, the program alerts the operator that ''N~ ~ATA'' are stored and the program loops until 2~33~3~

any key lS pressed. On key hlt the program returns to the Msln ~enu 3010. If one of the ANS tests have beer completed, the program dlsplays the flrst selected ANS test result followed by the remaLning test results. After ali results have been dlsplayed, the program returns to the Main .~enu 3010. In addition to transmltting the ANS test results to an external data display means, the operator may choose to trsns~1t the results to an external data handllng means whlch may include a printer, computer, or other data handling means. Transmltting ANS test results is also referred to as 'prlnt1ng throughout the descr1ptions and flow charts that follow. This prlntlng optlon ~026 may be accessed by pressing Key ~ on the Maln henu 3010.
Prlor to transmittLng the ANS test results to an external data handling means, Block 3028 first checks to see if any ANS
results have been computed and stored ln Block 3054. If no tests have been done , the program bypasses the other print options and returns to the hain Menu 3010. If a completed test(s) and result C5) are present, the program advances to Input 3030. The operator is prompted to enter the Patient ID and Patlent Age. The input Patient Age is used to correlate the ANS test results with age-matched values . This automated correlaticr. 1S unique to this invention and is critlcal for accurately assesslng the extent of autonomic nervous system functioning beca~se the EiI hat~o decllnes appreciably with age. Therefore, dlfferent value ranges are required to account for the normal aging prccess. The program 2 ~

advances to Report Format 3~3' where the operator lndlvl uall=es the report for~at ,lf so deslred. If the Strlp Prlnt~ng Optlon lS selected, a mlnLmum of one mlnute of ECG data recordec during the predetermlned breathing reglmens w~ll be prlnted. The actual amount of ECG recording to be printed lS based on the next selectlon by the operator. A LONG report wlll conslst of qll ECG
data recorded durlng the predetermlned breathing reglmens wheress a aHGRT report wlll consist of only the lnltial mlnute , or first SlX breath cycles, ot the paced breathing reglmens. The Prlnt Grld option will determlne whether a grld will be printed behind the ECG data. Regardless of the selected format, each report will contaln the following information: Heading, Patient ID number, Patient Age, Date, Software verslcn, ana Procedure Text. The Procedure Text describes which ANS tests were performed. Once all optlons have been selected, the oper~tor ic prompted to choose either to transmlt the report , or to abandon the print task and return to the hain henu . If the report lS
trsncmitted, the program advances to Prlnt Report 3C3~. The printed report will output the ANS test results and their corresponding age-matched values in addltion to the raw ECG data.
The printed report will also contain the .ollowins in~ormatlon based on the prior selectlons stored in c,c_ks 302G
and 3032. First, the Histcgram option lS checked in ~io=k 30~0.
lf lt has not been selected, the program checks the 5trlp ~ptio..
ln block 3032. If the E~I test was selected and perf_rmed, a - 2~3~l~33 table 15 pr~nted based on the data stored ln ~lock ,054 W~lC~
l~sta each breath cycle number ln block 305~, the inhaiatlon heart beat 1nterval chosen for each breath cycle number and lts duratlon 1n mlll1seconds, the exhalatlon heart beat 1nterval number chosen ~or each breath cycle number and lts duration 1n mlll1seconds, as well s the duratlon totals ln m1ll1seconds for both inhslat;on and exhalation perlods comprislng the breath cycles. Thls is followed by a hlstogram whlch graphs the heart beat lntervals over the bre~thlng reglmens, referred to as tlme . This is followed by a graph of the frequency dlstrlbution of the heart beat intervals over time. If the Valsalva test was completed the 'Jalsalva hlstograms are also printed. One graph for each test lS printed showing the heart beat lntervals over time. Each graph lS labeled with the correspondlng Valsalva test number. The Strip option is checked lastly in block 3032 . If thls option was selected, the str.ps are prlnted and annotated with the followlng ln~^ormation: Inhale or Exhale, Breath Cycle Number, Interval number for those intervals used to compute the E/I Ratio and/or other ANS test result, and the interval selected in each breath cycle is printed 1n bold to hlghllght the automatlc selection by the apparatus.
.n addition a page top heading llsts the ~atient ID, the page number and the date. At the conclusion o~ the strip printing the program returns to the Main Menu 3010.
The Editing option of the apparatus corresponds to Key 7 on 2~3~33 the Maln Menu 3û10. As prev~ously explslned, the E/I Ratlo 1~
derlved from selected heart beat ~nterv~;s ln each breath cycle whlch have been automatlcally selectec by the apparatus upon completion of the predetermlned breathlng reglmens comprislng the ANS tests. The operator, however, has the optlon to manually reselect the heart best lntervais to be used for recomputlng the E~' Ratlo andior any other ANS test result. Some or all of the intervals whlch had been autcmatlcally selected by the apparatus may be reselected and manuaily lnput into the apparatus for automatlc recomputation.
Upon selectlon of the EDIT E~I option 3056, the program checks to insure that the E/I test was completed ln block 3058. If no test was done the program returns to the Main Menu. If the test has been completed, the program dlsplays breath cycle data in Block 3060 whlch ~s obtalned from data storage Block 305~. The data 1~ displayed on the external display ~eans including the specif lC bresth cycle (inspiratory or expiratory) of the predetermined breathing regimen the heart beat interval automatically selected by the apparatus for that breath cycle which was used ln the ANS test result computation, and the start and end heart beat intervals of that same breath cycle. The operator may manually 1nput a new heart bes~ interval 306~ from t~e keyboard as represented by a numDer fro~ the range of numbers representing the heart beat lntervals between start beat and end beat for tha. breath cycle as d1splayed ln block 3060. A check ~6~33 ~s made for vaild '-n~ry Ln block 3060. A l~ne lS sounded to lndicate a non-vai.~ entry and the program -eturns to 30~2. A
vaild selectlon allows ~he program to advance t3 the next breath cycle of the predetermlned breathlng regl~e.. untll all breath cycles have been revlewed. The E/I Ratlo and~or other ANS test result using the reselected heart best 1ntervai value is automatlcally recomputed in block 30~4. The EfI ~atlo and/or other ANS test result may be recomputed untli the ANS test result is acceptable to the ~perator. The program returns to the Maln Menu 3010 after each recomputation.
Referrlng now to Figure 4, the RUN TEaT Block 3040 from Figure 3 lS shown in more detail. This biGc~ is repetltively executed throughout the running of each ANS test. At the start of any autonomic nervous system test, the program advances to the audiovi~ual branch _040-1 of RUN TEST 3040 whlch is responsible for issulng audiovisual messages on the external display means as to the detection of lncoming signals and lnstructions to gu;de the patient in performlng the predetermlned physical reglmen.
Once signals are rece:ved, the program advances to Beat Detectlon 3040-2 to determine whether the slgnals are _CG signals generated from the heart of tne patient or if they are artifactual. Beat Detection is described in more detail in Flgure S. The prcgram must then distingulsh whether the Beat De_ection lS occurring during Setup 30~0-3 wherein the patient may practlce the predetermlned breathlng regimen before the 3tsrt of the actual ~33i~3~

test run, or durlng the ANS tes' ~tsels ~040~ t.~e program 15 ln the ~etup phase,the program ~dvances to B10CK 3040-4 tO
determlne whether the Setup phase ls completed. The ~etup lasts sor a mlnlmum o one mlnute. Is one minute has elapsed, ana lf the patlent and~or techniclan depresses a button on the external apparatu-~ slgnallng the onset of the actual test, the program advances to 30~0-S where a check lS made on the ECG slgnal durlng the ~etup phase to determ~ne ~hether the ECG sLgnals meet criterla as descrlbed ln more detail in Figure 5. 1, errors are present, the program returns to B10Ck 3050 where;n additlonal error checking ~s completed. If, however, one mlnute has not elapsed, or the patlent and~or techniclan has not aepressed the start button when the program lS at Block 30~0-4, the prGgr~m returns to Block 3040-1 where audiovisual lnstructlons will continue to be displayed. When the program returns t Block 3040-3, and the predetermlned breath;ng regimen is not in the Setup phase because an external slgnal has been received lndlcating the end o the Setup, the program branches to the actuai test port-on 3040-6 of the predetermined breathlng regimen in B_ock 3040-6.
When predetermined breathing reglmen ls completed ir. Block ~0~0-~, the progr~m advances to Block 3050 whlch 13 -escribea in detall in Figure 3. I the prede.ermlned breathing regimen has not been compieted accordlng to crlteria prevlGusly jescrlbea for each ANS test, the program returns to Block --040-1 where audiovi3ual instructions contlnue.

- 2 ~ 3 ~

Referrlng now to Flgure 5, tr.ere lS shown a de~llea -^chematlc of Beat Detectlon 310ck ~4~-~ from F~gure ~ fter recelvlng the ~es,age from Block 3040-1 that the au~lo~;_susi portlon has begun, the program checks ~or the presence of peaks ln ~lock 5000. If peaks are detected, the signal pesks are checked to make sure they are of sufflclent amplitude which may be either positlve or negative deflectlons. ?e~ks are also checked for frequency. If the peak amplltude or peak rate a~erage falls a~ove or below a predetermined value, the program ~xits Beat Detection Biock 3G40-2 and contlnues with the nex step 30~0-3 of the RUN Test Block 3040. If peak signal is valid, the width of the peak 1S measured ln Block 5005. If the Peak Width e~ceeds a predetermlned width, the program exits the Beat Detection Block and returns to 30~0-3 as above. If the peak wldth 1S within an acceptable range, the program proceeds to 501C where the number of peaks are counted withln each peak width. ._ too many peaks are detected within the acceptable peak wldth, the program exits the Beat Detection Block and returns to 3040-3 as above. If the number of peaks are wlthin the acceptable rar. e of peaks for any glven peak width, the program advances to 50;_. The distance between each peak group is calculated. If the iargest peak among the peak group lc too close to the iast detectec peak, the program exits the Beat ~etection ~lock and returns tc __40-3.
If the peaks occur at a distance that correlate to the 1..~.eren.
physiological capabilites of the heart, the program prccee=s to 2 ~ 3 5u_0. A comparlson 15 made between one peak and _he next to ma~
certaln that the peaks are a manlfestatlon of heart actlvlty anc not just random nolse. It- consecutl~e peaks are dlss mllar, the program exlts the Beat Detectlon ~lock and returns to 3040-~ 25 above. If the peaks are slmilar, the program contlnues on to ~lock 5025 to determlne whether the iast peaK ~n the group has been detected. Thls completes the dlscrim_natLng steps of de lning an ECG generated by the heart of a ?atient versus a signal orig1nating from a source cther than the human he&rt. ~hen the last peak has been found, an audiovisuai ~essage 15 displayec denoting that a beat was found ln Block 5030. Once it has been declded that the ECG slgnal is a beat, furt,her analysls 15 performed to deflne whether the RS 15 a ncrmal beat or an "abnormal' beat in Block 5035.
Upon entry to the HIGH LEVEL BEAT DETECTION routlne, the routine contlnues to make an analysis of both the peak ltseif and the peak cluster ln order to refine the beat profile.
The beat is checked for prematurlty and width. If the beat does not exceed the prematurlty and width crlterla, the program proceeds tG ~lock 5040 where the time of the largest peak 15 stored for future c&i-uiations. If the beat exceeds the prematurlty and width criteria, the program branches to Block 505~ where the type of abnormallty is determLned. Block 5050 is descrlbed in more detaii ln Figure 5. Once the abnormal beat is classified, the program ret~rns to B10CK 50~0 -~nere the time and ~2 ~333~33 type of ~bnormai beet l5 logged and stored. .ne program then returns to Block ,0~0-3.
Figure ~ and some of lts correspond~ng ~escr~ptlons have been reproduced from U.S. Pstent No. 4,6,~,14~ to ~_ox et al who co-lnvented thls new lnventlon. This portlon of the program descrlbec ebnormel beat detection and snalysls. Speciflcally ~iock 51~ ''determines if the prev;ous beat was a suspected VPB.'' If not, the program proceeds to Flgure 7 vla lir.e 11a for further analysls. "If the previous beat was a su pected VPB, the compensat_ry interval lS caiculated for the purpose of chec~ing for the presence of a compensatory pause'' in ~lock 520 '-which would lndlcate that the suspected VPB was a tr-_e VPB. The current average pulse int~rval lS added to the tlme at whlch the ~RS
complex preceding the suspected VPB is known to nave occurred.
Thls re~uit represents a polnt in time at whlch a normal beat following a VPB would fall lf a compensatory pause were present.
If the current beat's time diverges from the calcuiated time by more thar. ~12.5% of the current average pulse lnterval, a compensatory pause is not lndlcated. The foregoing procedure is repeated three additional t~mes with the everage puise ~nterval being adced to thee previously calculated compensat_ry interval each tlme. This procedure allows for the ver,fication of lnterpolated VPBs as well as the possibiiity of verlfication of V~s whl_-~ are followed by ~'undetected~' ~RS compiexes. If no verificat:on can be made by the end of the fourth a..empt, " the ~3 2~S ~33 program advances ~o F~gure 7. 'lf verl~lcatlor. _s poss;~ie, the program proceeds to ~10CK 5~G where the suspecte~ VPB .s labellec as a conflrmed VF~-'. The rout~ne advances to Bloc~ lOl~ ~n F~gure 7 (corresponds tc rigure lu Ln U.~.P. ~,67~ 4i ''where the loglc looks at the results of the analys;s performea for the current beat and the 13s_ tWO beats to determlne whether all three beats exhlblt ~PB characterlstics. If they do, the analyses move to Block 1u-~ where an alarm lag lS set for a condltlon lndicatlve ot- ~entricular Tachycardla, and thls lnforma~lon is sent to Alarm Block 1070 vla line 10g~. If the three beats exsmlned at Block 1010 do not exhlblt ~P~ characteristlcs, the analyses proceed to Block 1030 where ~he results of the analyses perormed for only the current beat and the last bea' are examined. If tAe logic determines that for both heats VPB
charaterist~cs were exhiblted, the analyses move to Block 10~0 where an alarm flag is set for a condition known as '-C~UPLT" and an appropriate signal is passed to Block 107~ via line 1099;
otherwlse the analyses move to Block lG50 where the logic determines lf the ST segment average lS Wlt hin acceptable limlts.
These limits are empirlcal values determined ~or any beat as a function o the isoelectrlc portion of the P~RST waveform associated wlth that beat.'' A chec~ lS maae to lnsure tha~ the beat has a ~ ml,lisecond segment wlth at least ~8 mliliseconds of slope equal to or greater than û.1 millimeter per m~ second.
1~ the beat does not meet these criterla there lS no further 2~33~

sttempt to +lnd an onset of J Po~nt and lr.,.-ad the program proceeds to Block 10,0. If , however, th~ ~eat ~eets the preliminary check +~or .he presence o+ an _. segment, tne lsoelectrlc amplitude of the beat lS calculate~ :n the followlnc manner: the ampl1tude o~ the beat lS sampled at a mlnlmum o+
four polnts prior to the onset time o+ the de.;ned aRS port1on of the beat. These po1nts are then averaged ~o arrlve at the isoelectric value. In the follow1ng operat~on the J Po1nt lS
located. The J Po1nt lS defined for these purposes as the term1nal polnt of the ~S complex wherein the actlve s~ope ceases. The J Point is in turn used to determlne the posltion 2nd amplitude of the ST Segment. A check is maae on whe.her the segment occurs w1thin an acceptable limit frc~ the ena of the beat. If so, the ST segment is tested to deter~ne if l~ occurs wlth1n an acceptable l1mit rom the onset of ..he beat. If the location of the ST segment falls within accepta~le limlts, the segment is tested for the following: does lt follow the last peak of the the beat?; is the segment amplltude w~th1n an acceptable limit from the isoelectrlc line as determlned 2~0ve?; and, is the sesment followed by perlod of qu1et slope hav.n~ iess than 0.^
millimeter of change ;n amplltude per m~ econd?. 'If the measured ST segment vaiue falls within the mlts, ..;e loglc proceeds to Block 107G. If the measured ST se_~ent value falls outside the limlts, the .ogic moves to Block iC---0 where an alarm flag is set to reflect either a condition ~or ''a~ SEGMF~T

2~ i33 L~E~RES_ION~ or ''ST SEGMENT ~L_'vATI~N', and a slgnal correspond~ng ~o the condltlon detected ~s sent to al~rm ~lock 1070 vla llne 1 u9~
"Block 1070, whlch recelv~3 lnformatlon passed through ~locx 1~50 rom llne l~9g and from l~ne ~9~, then reads the ~larm fiags set and dlsplays alarmA correspondlng to the ~arlous detected _ondltlons of the devlce and the patlent'', lf aiarms are enabled.
''In additlon, Block 107u upcates the stored counts for VPBs, couplets, ventrlcular tachyc~rdla and thelr duration, as well as the total ST segment duration." ~he loglc then proceeds to Block 5040.
Regardless of the categorlzation of the abnormal beat or the level of ST depresslon, the tlme of the largest peak lS s.ored along with the abnormal beat iabel for future calculations ln Block 5040. The accurate identl~lcatlon of abnormal beats and the time of thelr occurrence is crltlcal when caiculating an ANS test result so that R-R intervals in which at least one beat lS
abnormal will not be included ln the calculatlon. An ANS test result can be skewed if abnormal beats were lncluded. Figure shows a detailed schematic of Block 3054 which lS a mult.-purpose caiculating and storing box for both the raw and computed àata obtained during each ANS tesL. Speciflcally, the caiculat1on of the Expiratory/Inspiratory Ratio, referred to -s _~I Ratlo, and the ffesn Circular Resultant, referred to as hC~, is shown. In ~lock 3054-;, the st~rt time for each of the SlX lnhaiatlon and 4~

~3~3~

exnal~t.on cyci2s relutlve to the st~rt tl~e OI the AN_ test are calcul~ed . T..e flrst beat ~or each cycle lS located . The minlmum heart beat lnterval, referred to as the R-R ~nterval, for nhaiat~on and the max1mum R-R lnterval for exhalation are located for each breathlng cycle comprised of one lnhalatlon followeà by one exhalatlon. The SlX m1nlmum lntervals are then added together and the slx maxlmum lntervals are summed. The sum of the minimum lnterv~ls lS then divided by the sum o~ the maxlmum lntervals and the quotlent lS multiplled by ''1~0-- to derive the EJI Ratio.
If the MCR optlon has been selected, the Mean ~ircuiar Resultant will begin to be calculated ln Block 3054-2. The tlme of each beat is converted to an angle relat1ve to lts dispiacement from the beginning ot- the 10 second resp1ration cycle, comprlsed o~ one lnhalatlon and one exhalat1on, 1n wh1ch the beat ls contalned. ~lne and cos1ne for each "beat angle" are computed in Block 305~-~ and runn1ng sine and cosine sums are accumuiated . The Mean Circular Resultant lS then calculated in B10CK 3054-~ by the formuia: MCR = the square root of ~the sum of the slnes d;v1ded by the number of beats~ squared plus the (sum of the cos nes divided by the number of beats3 squaredJ.
Upon completion the program returns to the Main Menu 3010.
Figure 9 depicts a àetalled schematic of Block 305~ o t~.e process for calculatlng two more A~S test resuits: Standard Deviation and ~oefficient of Variation. The Standard Dev1ation lS

2033~3~
calculated by first summing all R-R intervals in Block 3054-5. The Mean Interval is then calculated in Block 3054-6 by the formula:
Mean Interval = (the sum of all R-R intervals divided by the number of intervals). In Block 3054-7, the Variance for each R-R interval is calculated using the formula: Variance = (the R-R interval -the Mean R-R interval) squared. The Variances thus derived are added together in Block 3054-8, and the Standard Deviation is calculated in Block 3054-9 according to the formula: STD DEV = the square root of (the sum of the variances divided by the number of R-R intervals). The Standard Deviation is then converted to milliseconds by multiplying the Standard Deviation by the quotient of 1000 divided by 256. In Block 3054-10, the Coefficient of Variation, which is a byproduct of Standard Deviation, divides the Standard Deviation value from Block 3054-9 by the mean R-R interval during the performing of the predetermined breathing regimen. The program returns to the Main Menu 3010.
Figure 10 details the process for computing the Valsalva Index in Block 3054. In Block 3054-11, the beat times during the first 20 seconds of the predetermined paced breathing regimen are scanned to find the maximum heart beat interval. The maximum interval is then checked to see if it is the first interval of the first twenty seconds of the predetermined breathing regimen. If it is the first interval, the average must be calculated separately where the length of the first heart beat interval is . .

~! ~r~ 6~ j "~ ~
-aaaea to the lengtM c-~ the second heart Deat lnterval whlch ln turn lS added to the iength of the thlrd heart Deat ,nterval, ~nc the sum l5 dlvlded by three to ylel~ an ~veraged ma~lmum neart beat interval. A check lS made to see lf the ma~lmum lnterva 7 lS the flnal interval of the forced exhalat~on cycle o the flrst twenty seconds. The flnal lntervai must also ~e averaged saparateiy to f1nd the maxlmum : the length of the last heart beat lnter~al of the _wenty second breathlng regimen lS added to the lengt.~ of the se~ond to last heart beat interval wh1ch ~n turn lS added to t;~e thlrd to last heart beat ln.erval. The sum lS then divlded by three to y1eld the finai three beat averaged maximum. If the max1mum interval during the entlre twenty second breatMing reg1men was ne1ther the flrst nor the last lnterval the three beat maximum average is calcuiated where:
the length of the ~ax1mum heart beat 1nterval is aaded to the lengt~ o the previous heart beat interval which lS ln turn addea ~o the length of the following heart beat lnterval and the sum lS
dlvided by three. .he maximum of the three averaged maximum values becomes the 'Jalsalva Average haximum.
The same series of operations is duplicated for the Valsalva M1n1mum 1n Block 3054-1- beg1nning with a scan for the min1mu~
lnterval from the 6~ second part of the predetermlned breathing regimen consisting of non-paced relaxed breathing follow1ng the twenty seconds of fGrced e~halat1on. The Valsalva ~dex is then computed for the flrst Valsalva test in Block 3054-i3. If ~ore 4g 2~3~33 th~n one 'vaisalva test was ~erformed, ~he Vaisaiva ~ndl_es fo, each test are summed, and .ner, dlvlded by the number o- '~'als31va tests per$ormed to derlve ~he Mean ~'alsalva Index. The prosram then returns to Maln Menu ~010.
Flgure 11 describes the Posture Index caiculatlon ln more detall than Rlock 3054. In Biock 3054-15, thc mlnlmum heart ~eat nterval is determined ~rom a speclflc range of heart beat lntervals between intervals 11 through lg slnce th;s lS the period of tlme in whlch the he2rt demonstrates the mlnlmum intervais upon standlng from a ly~ng down posltion. In Block 3054-15, the m~xlmum lnterval is then calculated between the 25tA and 35th heart beat lnterval after standlng. The maxlmum interval is then divided by the mlnlmum interval to derive the Posture Index in Block 305~-17. The program then returns to Maln Menu 3010.

Claims (32)

1. Automated apparatus for monitoring heart beat signals generated by the heart of a patient to whom it is attached, comprising:
means for performing continuous real-time analysis of said heart beat signals derived from said patient, means for storing one or more normative data bases for automated correlation of test result to age-matched values, means for recognizing normal and abnormal beats, means for diagnosing each of said abnormal beats, means for providing audio-visual signals to the patient to instruct said patient in at least one predetermined physical regimen, whereby the patient may perform said at least one predetermined physical regimen without any additional prompting or instruction, and means for outputting the results of said analysis.

2. The apparatus of claim 1, wherein said means for outputting results includes means adapted to cooperate with external data handling means.

3. The apparatus of claim 2, wherein said means adapted to cooperate comprises optical emitter means adapted to be coupled to an optical receiver, whereby said results can be output from said automated apparatus to said external data handling means, and said external data handling means may comprise a printer, a modem, a computer, or other external data handling means.

4. The apparatus of claim 2, wherein said means for outputting results further comprises display means, and wherein said display means is also the visual portion of said audio-visual signal providing means.

5. The apparatus of claim 1, wherein said predetermined physical regimen is a predetermined paced breathing regimen.

6. A computer implemented method of performing a test of a patient's autonomic nervous system comprising monitoring every beat of the heart of said patient to detect and correlate variations in heart functioning during a predetermined physical regimen to autonomic nervous system functioning, comprising the steps of:
attaching sensing means to the patient to sense the heart beat of said patient, using the output signal of said sensing means to produce heart beat signals, analyzing said heart beat signals, determining from said analysis of said heart beat signals if each said signal is representative of one of a normal or abnormal heart beat or an artifact, issuing continuous audio-visual instructions to the patient to guide the patient in performing said predetermined physical regimen, storing data during the patient's performance of said predetermined physical regimen, performing all of the aforesaid steps in a predetermined quantity based on said heart beat signals only to thereby define a test, correlating the results of said test with age-matched values to accurately assess the extent of automatic nervous system function, and outputting the results of said test upon conclusion of said test.

7. The method of claim 6, wherein said predetermined physical regimen is a predetermined paced breathing regimen.

8. The method of claim 6, wherein said outputting of results step includes outputting a portion of said results.

9. The method of claim 6, and performing all of said steps continuously during the running of each said test.

10. The method of claim 6, wherein said test is performed because said patient is at least suspected of having at least one of diabetes, a predisposition to sudden death, alcohol addiction, coronary artery disease, muscular dystrophy, parkinsonism, HIV
infection, Shy-Drager syndrome, impotence, sleep apnea, toxic neuropathies, and any other disease which affects the autonomic nervous system.

11. A computer implemented method of evaluating autonomic nervous system functioning comprising the steps of:
instructing a patient whose autonomic nervous system is being evaluated to perform a predetermined physical regimen, sensing each beat of the heart of said patient, determining by analyzing said heart beats, whether or not each said heart beat is representative of a normal or abnormal heart beat, producing a signal corresponding to each said sensed heart beat, calculating the time from a selected point on one signal to the corresponding point on the next succeeding signal, correlating said predetermined physical regimen with said calculating step, storing raw data from said steps of producing, calculating, and correlating said signals, correlating the results of said test with age-matched values to accurately assess the extent of automatic nervous system functioning, and providing at least one autonomic nervous system test result substantially instantaneously based on said calculating, correlating, and storing steps.

12. The method of claim 11, wherein said predetermined physical regimen is a predetermined paced breathing regimen.

13. The method of claim 11, and performing said instructing step for a plurality of times.

14. The method of claim 11, and the additional step of classifying each said sensed heart beat as normal or abnormal.

15. The method of claim 14, and the further steps of determining an autonomic nervous system test result based on said sensed normal beats only comprising:
identifying said selected point on one said sensed heart beat and the corresponding selected point on the next succeeding said sensed heart beat, determining if said next succeeding such sensed heart beat is normal, repeating said identifying step if said next succeeding such sensed heart beat is not normal as determined by said determining step, and calculating the time between said corresponding selected points only if both said succeeding sensed heart beast are normal, whereby the accuracy of said autonomic nervous system test result based on said calculating step is increased due to the inclusion of normal beats only in said calculating step.

16. The method of claim 14, and the further step of identifying each beat classified as abnormal in said last mentioned classification step as an abnormal beat originating from the heart of said patient or as an abnormal beat originating from a source other than the heart of said patient.

17. The method of claim 11, and performing said producing step to produce an EKG signal, and selecting said selected point on said succeeding signals from the group consisting of the R-wave, Q-wave, QS-wave, P-wave, T-wave, or any other point on said EKG
signals.

18. The method of claim 11, wherein said autonomic nervous system test result is the Standard Deviation and the further steps of:
determining the mean time of said calculating step during predetermined paced breathing regimen based on said instructing step, and relating all of said times derived from said calculating step to said mean time to provide said Standard Deviation indicative of said autonomic nervous system function.

19. The method of claim 18, wherein the performance of said relating step is automated and substantially instantaneous.

20. The method of claim 11, wherein said autonomic nervous system test result is the Mean Circular Resultant and the further steps of:
identifying the time of onset of each cycle of breathing comprising said predetermined physical regimen, calculating the time between the occurrence of said selected point of each said sensed heart beat relative to said time of onset of each said cycle, converting said times produced in said calculating step to vectors comprised of X and Y components, repeating said converting step for each said cycle, computing a single average vector of said X and Y components for all said cycles, and determining a Mean Circular Resultant indicative of said autonomic nervous system function.

21. The method of claim 20, wherein the performance said determining step is automated and substantially instantaneous.

22. The method of claim 11, wherein said autonomic nervous system test result is the Valsalva Index and the further steps of:
identifying the maximum time of said calculating step during said predetermined physical regimen based on said instructing step, identifying the minimum time of said calculating step during a predetermined time following the completion of said predetermined physical regimen based on said instructing step, and correlating said maximum and minimum times to provide said Valsalva Index indicative of said autonomic nervous system function.

23. Automated apparatus for editing a calculated test result which has been initially based on automatically selected portions of raw data derived from monitoring of heart beat signals during the performance of at least one predetermined physical regimen, comprising:
means for outputting said calculated test result, means for storing one or more normative data bases for automated correlation of test result to age-matched values, means for outputting automatically selected heart beat intervals selected from said raw data which were used to calculate said test result, means for outputting said raw data, means for inputting manually selected heart beat intervals selected from said raw data that differ from said automatically selected heart beat intervals, means for recalculating said test result based on said manually selected heart beat intervals, and means for outputting said recalculated test result, whereby said calculated test result is edited.

24. The apparatus of claim 23, wherein said means for outputting said test result further includes means adapted to cooperate with external data handling means.

25. The apparatus of claim 23, wherein said means adapted to cooperate comprising optical emitter means coupled to an optical receiver, whereby said test results can be output from said apparatus to said external data handling means, and said external data handling means may comprise a printer, a modem, or a computer.

26. The apparatus of claim 23, wherein said automated apparatus is self-contained and portable.

27. The apparatus of claim 23, wherein said predetermined physical regimen is a predetermined paced breathing regimen.

28. An automated apparatus for evaluating the function of a patient's autonomic nervous system comprising:
means for storing one or more normative data bases for automated correlation of test result to age-matched values, means for sensing signals, means for determining if said sensed signals are representative of a heart beat or an artifact, means for classifying said signals representative of a heart beat as normal or abnormal, means for performing continuous real-time analysis of said signals derived from said patient, means for providing audio-visual signals to said patient to instruct said patient in at least one predetermined physical regimen, means for correlating said signals with said at least one predetermined physical regimen, means for automatically calculating test results based on said correlating step for evaluating said function of the autonomic nervous system of said patient, means for outputting said test results, means for outputting said signals, means for interfacing said outputting of said test result with external data handling means, means for editing said test result, and means for imputting portions of said signals for automatic recalculation of said test result, and display means forming part of all of said means for providing audio-visual signals, all of said means for outputting, said means for inputting, and said means for editing.

29. The apparatus of claim 28, wherein said predetermined physical regimen is a predetermined paced breathing regimen.

30. A computer implemented method of editing at least one autonomic nervous system test result which has been previously calculated from automatically selected heart beat intervals of recorded raw data, comprising the steps of:
providing an output means, outputting at least a portion of said automatically selected heart beat intervals, outputting at least a portion of said recorded raw data, identifying said portion of recorded raw data that differs from said automatically selected heart beat intervals for recalculating said test result, providing input means, inputting said portion of recorded data identified in identifying step, recalculating said test result based on said data input in said inputting step, correlating the results of said tests with age-matched values to accurately assess the extent of autonomic nervous system functioning,and outputting said recalculated test result, whereby the accuracy of said test result is increased due to the said method of editing by an operator.

31. The method of claim 30, wherein said recalculating step is performed automatically and substantially instantaneously.

32. The method of claim 30, and repeating of said steps of identifying, providing, inputting, recalculating and outputting until said test result is acceptable to said operator.