WO2004052192A1 - Physiological condition monitor - Google Patents

Abstract

A device for monitoring a physiological condition of an individual, the device including: a monitoring unit (14) composed of at least one electrode (12)constructed to be placed in contact with the skin of the individual to produce a signal corresponding to the physiological condition, an amplifier coupled to the electrode to amplify the signal produced by the electrode, and a signal processing unit coupled to the amplifier to process the amplified signal from the amplifier in order to derive an indication of the physiological condition; and an attachment member (22) for securing the unit to the skin of the individual at a selected location with the electrode in contact with the skin.

Description

TITLE PHYSIOLOGICAL CONDITION MONITOR

CROSS REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of Provisional Application 60/432-229, filed December 11, 2002, the disclosure of which is incorporated herein by reference.

BACKGROUND OF THE INVENTION [0002^'] The present invention relates to the monitoring of physiological conditions of an individual, and in particular to devices that can be worn on a long term basis by an individual .

[0003] The invention relates particularly to the monitoring of a number of conditions associated with cardiac disease. Several of these conditions and their implications will be discussed below, with the numbering in parentheses referring to the references listed at the end of this specification. [0004] The numbers in parentheses identify relevant references that are cited at the end of this specification.

Silent: ischemia background

[0005] Soon after the publication of Heberden's classic description of angina pectoris, the discrepancy between the extent of anatomical coronary artery disease and patients' symptoms was noted. It has since been recognized that myocardial ischemia and infarction can occur without pain; infarction is sometimes discovered by electrocardiography, and myocardial ischemia might be assumed retrospectively after the postmortem demonstration of substantial coronary artery disease. __ In particular,_ reversible silent myocardial ischemia has been investigated by using ambulatory electrocardiographic monitoring, and is a common finding. As many as 70% of episodes of myocardial ischemia in patients with coronary artery disease may be asymptomatic, and the incidence of painless events for acute myocardial infarction is estimated to be about 30%.

[0006] Patients with silent ischemia have been stratified into three categories by Cohn:

[0007] Type I Silent Ischemia: The first and least common form, type I silent ischemia, occurs in totally asymptomatic patients with obstructive CAD (which may be severe) , and these patients do not experience angina a t any time; some type I patients do not even experience pain in the course of myocardial infarction. Epidemiological studies of sudden death, as well as clinical and postmortem studies of patients with silent myocardial infarction and studies of patients with chronic angina pectoris, suggest that many patients with extensive coronary artery obstruction never experience angina pectoris in any of its recognized forms (stable, unstable, or variant) . These patients with type I silent ischemia may be considered to have a defective anginal warning system .

[0008] Type II Silent Ischemia: The form that occurs in patients with documented previous myocardial infarction.

[0009] Type III Silent Ischemia: A frequent form of silent ischemia, occurring in patients with the usual forms of chronic stable angina, unstable angina, and Prinzmetal angina. When monitored, patients with this form of silent ischemia exhibit some episodes of ischemia that are associated with chest discomfort and other episodes that are not—i.e., episodes of silent (asymptomatic) ischemia. The "total ischemic burden" in these patients refers to the total period of ischemia, both symptomatic and_asymptomatic. Mechanisms of silent ischemia

[0010] It is not clear why some patients with unequivocal evidence of ischemia do not experience chest pain whereas others are symptomatic. Maseri has proposed that silent ischemia results from a variable combination of decreased sensitivity to painful stimuli and coronary microvascular dysfunction. Investigation into the causes of silent ischemia has focused primarily on five areas:

[0011] (1) The association between diabetes and both silent ischemia and "painless infarctions" has been attributed to an autonomic neuropathy (2, 3).

[0012] (2) Patients with silent ischemia have been shown to have a high threshold for other forms of pain, such as that resulting from electrical shock, limb ischemia, or cutaneous application of heat or from balloon inflation in the coronary artery.

[0013] (3) Hypertensive patients who demonstrated a higher incidence of "silent" ischemia have been shown to have higher pain thresholds and lower reactions to tooth pulp stimulation than normotensive subjects. It has been postulated that these patients produce an excessive quantity of endogenous opioids (and endorphins) that raise the pain threshold, but the existence of such a mechanism is debated.

[0014] (4) A more recent area of investigation suggests that silent ischemia in some patients may not be due to peripheral nerve dysfunction but instead be the result of a defect in the cerebral cortex. Frontal cortical activation appears necessary to experience cardiac pain, and some evidence indicates that in patients with silent ischemia, afferent pain messages from the heart are subject to abnormal neural processing. The role of psychosocial factors in the _ perception of pain is controversial. Diagnostic aspects of silent ischemia

[0015] Transient ST segment depression of 0.1 mV or more that lasts longer than 30 seconds is a very rare finding in normal subjects (4) . Patients with known CAD show a strong correlation between such transient ST segment depression and independent measurements of impaired regional myocardial perfusion and ischemia determined by rubidium-82 uptake as measured by PET. In patients with type III silent ischemia, perfusion defects occur in the same myocardial regions during symptomatic and asymptomatic episodes of ST segment depression. Other methods of detecting "silent" ischemia include measurement of the left ventricular ejection fraction with a "nuclear vest" or the presence of regional wall motion abnormalities and perfusion defects on echocardiography or radionuclide scintigraphy (5) .

[0016] The extensive use of ambulatory ECG monitoring has led to a greater appreciation of the high frequency of type III "silent" ischemia. It has become apparent that anginal pain is a poor indicator and underestimates the frequency of significant cardiac ischemia (6). Analysis of ambulatory ECG recordings among patients with CAD who had both symptomatic and silent myocardial ischemia showed that 85 percent of ambulant ischemic episodes occur without chest pain and 66 percent of angina reports were unaccompanied by ST segment depression (7). Therefore, it has been suggested that overt angina pectoris is merely the "tip of the ischemic iceberg." Episodes of silent ischemia have been estimated to be present in approximately half of all patients with angina, and a higher prevalence has been reported in patients with diabetes (8) ,. , . ___ „ _ _ . ___ [0017] Long-term electrocardiographic (ECG) recording is fundamental to detect and characterize episodes of myocardial ischemia in patients with suspected or documented coronary artery disease (CAD) . In clinical practice, long-term ECG monitoring is principally achieved by Holter ECG recordings (H-ECG) , which is the method used in the vast majority of studies and trials on silent ischemia in the medical literature. Detection of spontaneous ischemic episodes during normal daily life by H-ECG has been found to have relevant prognostic implications and can assist in therapeutic decisions. Indeed, H-ECG can also provide findings contributing to define the pathophysiologic mechanisms responsible for transient ischemia in individual patients. [0018] After the early technical difficulties in the correct reproduction of low-frequency ECG signal, modern technology has allowed reliable reproduction of the ST segment by H-ECG devices. Furthermore, the possibility to detect myocardial ischemia by H-ECG has been improved by monitoring two bipolar chest leads. Monitor leads should always include CM5 (V5), as it is the single lead with the highest sensitivity in relieving ST segment depression, independent of the location of myocardial ischemia. Recently, H-ECG recorders able to monitor three leads, and also a system which allows recording of 12 leads, have become available. Nevertheless, the usefulness of more than 2 bipolar leads for improving detection of subendocardial ischemia has been questioned. In one study, the addition of a third H-ECG lead improved sensitivity for detecting subendocardial ischemia only from 94% to 96%. [0019] According to Bayes theorem, the probability that transient ST segment depression on H-ECG actually represents myocardial ischemia varies according to the clinical features of the patient, being as much as greater as higher is the pretest likelihood of CAD. In fact, "ischemic" ST segment changes have been reported in 2% to 30% of asymptomatic apparently healthy subjects, but the vast majority of them will not have significant CAD. A greater severity of ST depression or the simultaneous presence of angina will increase the likelihood that the ECG alteration is actually caused by myocardial ischemia.

[0020] The ischemic meaning of ST depression on H-ECG is usually established with reference to the presence or absence of hemodynamically significant epicardial coronary artery stenosis at angiography. However, coronary angiography may not be the ideal "gold-standard" for the interpretation of ST segment depression, because myocardial ischemia can occur in the absence of coronary stenoses, as in microvascular angina or in subocclusive vasospastic angina.

Silent ischemia detection in chronic stable angina

[0021] Although in patients with chronic stable angina the sensitivity of H-ECG in detecting myocardial ischemia has sometimes been reported to be similar to that of exercise testing, it is actually lower. Indeed, the occurrence of transient ischemic episodes during daily life is strongly correlated to the workload at which ischemia appears on exercise test, being greater in patients with low ischemic threshold and lower in those with no or high-workload ischemia (9) . Thus, H-ECG has low additional diagnostic value in these patients, although it may reveal ischemia in about 10% of those with negative exercise test. These latter are usually patients with a high variability of ischemic threshold, likely due to significant vasomotor changes. Furthermore, _H-ECG may represent the first diagnostic test in patients who are unable to undergo exercise test.

[0022] H-ECG is useful to define the number, severity and duration of ischemic episodes during normal daily life, as well as their relationship with activity and daily hours.

Thus, H-ECG has shown that episodes of subendocardial ischemia have a typical circardian distribution, with a first peak in the morning hours and a second peak in the afternoon.

[0023] H-ECG has also shown that increased myocardial oxygen demand has a predominant role in the induction of ischemia in patients with stable angina, as heart rate (HR) significantly increases prior to ischemia in the majority of episodes, whereas it shows more limited changes in patients with unstable angina. [0024] In patients with stable CAD, H-ECG has also shown that :

[0025] 1) HR at the ischemic threshold (i.e., 1 mm ST depression) is lower during spontaneous ischemic episodes than during ischemia induced by exercise test (10, 11); [0026] 2) HR at 1 mm ST depression presents wide variability among spontaneous episodes;

[0027] 3) HR does not increase prior to ischemia in a significant number of ischemic episodes (10-12).

[0028] These findings suggest that a primary impairment of coronary blood flow, caused by vasomotor changes, also plays a significant role in determining the occurrence of ischemia in these patients.

[0029] H-ECG is also useful to characterize episodes of ST segment depression in patients with cardiac syndrome X (i.e., anginal pain, positive exercise test, angiographically normal coronary arteries) , which is believed to be caused by coronary microvascular disease (13) . Episodes of ST depression in these patients present findings similar to those of stable CAD patients (14, 15).

Prognostic implications of silent ischemia detection by H-ECG [0030] Episodes of myocardial ischemia, regardless of whether they are symptomatic or asymptomatic, are of prognostic importance in patients with CAD. In asymptomatic patients, the presence of exercise-induced ST segment depression has been shown to predict a fourfold to fivefold increase in cardiac mortality in comparison with patients without this finding (16).

[0031] The presence of myocardial ischemia on ambulatory ECG, whether silent or symptomatic, is associated with an adverse cardiac outcome, particularly if the episodes are frequent or accelerating (17, 18).

[0032] What previously has been less clear is whether the detection of asymptomatic episodes of ischemia on ambulatory ECG adds independent prognostic information over and above that provided by the results of the stress test and the frequency and severity of symptoms. In the ACIP Study, among patients treated medically, myocardial ischemia detected by ambulatory ECG and by an abnormal exercise treadmill test were each independently associated with adverse cardiac outcomes (19, 20) . Moreover, ischemia detected by ambulatory ECG monitoring did not correlate with the presence and extent of ischemia as quantified by stress SPECT scintigraphy, which suggests that these techniques detect different pathophysiological manifestations of ischemia (21) . Further support for this concept is provided by angiographic evidence from the ACIP Study data base, in which patients with ischemia and ambulatory ECG_ were more likely to have multivessel _^CAD, severe proximal stenoses, and a greater frequency of complex lesion morphology, including intracoronary thrombus, ulceration, and eccentric lesions, than were patients without evidence of ischemia on ambulatory monitoring. The presence of severe and complex CAD may partly explain the apparent independent effect of silent ischemia during ambulatory monitoring on prognosis (22) .

[0033] In summary, silent myocardial ischemia is clinically important because it is associated with poor prognosis after an event such as an episode of unstable angina or myocardial infarction. Most dramatically, it has been assumed to exist in patients in whom coronary artery disease presents as sudden cardiac death. Silent ischemia has also been found during exercise in survivors of cardiac arrest and in patients with life-threatening arrhythmias. [0034] Detection of silent ischemia is associated with increased risk of cardiac events in several groups of CAD patients

Myocardial infarction [0035] There have been several reports on the prognostic value of silent ischemia on pre-discharge H-ECG in survivors from acute myocardial infarction (23-25) , in a large study on 406 patients, reported that 1-year mortality was 11.6% in patients with transient ischemia, but only 3.9% in those with no ischemic episodes (p=0.009) on 48-hour H-ECG. Similarly, major cardiac events (death or reinfarction) were 23.2% and 9.6% in the two groups, respectively (p=0.001). Silent ischemia on H-ECG had independent prognostic value and appeared particularly useful in the prediction of events in high-risk subgroups of patients, including those excluded from exercise test and those with lo left ve_ntricular ej_ection fraction. Unstable angina

[0036] Many studies have shown that transient ischemia on H-ECG performed early after hospital admission is among the major (and likely the most important) predictors of cardiac events in patients with unstable angina. Gottlieb et al . (26) reported that intra-hospital myocardial infarction occurred in 16% of patients with and in 3% of patients without episodes of transient ischemia on H-ECG (p=0.005). They also showed that a total ischemic burden >60 minutes in the 24 hours was more predictive for total coronary events (including revascularization procedures) . These data were confirmed by other studies (27).

Chronic stable angina

[0037] The prognostic role of H-ECG in patients with a history of stable CAD is more controversial. In the Total Ischemic Burden Bisoprolol Study (TIBBS) (28) on 520 patients, the occurrence of major cardiac events (death, myocardial infarction, unstable angina) at a follow-up of 12 months was 4.7% in patients with <2 episodes of transient ischemia, but 12.1% in those with >2 ischemic episodes (p<0.005). Other studies, however questioned the prognostic value of silent ischemia in patients with stable heart disease (29) . [0038] The reasons for these discrepancies are not clear.

However, different selection criteria of patients, end points, H-ECG recording and analysis, and therapeutic approaches may have contributed. In our opinion, the detection of transient silent ischemia at H-ECG in patients with stable CAD should likely be considered as a risk factor for future events.

However, it should be considered_that the _^detection of ischemia in these patients usually occurs in those with low workload ischemia at exercise test, who already are at higher risk (30) . Thus it is not clear whether silent ischemia on H- ECG may actually add prognostic information compared to those provided by a careful assessment of exercise results, including not only ECG variables, but also clinical (exercise tolerance, symptoms) and hemodynamic (HR, blood pressure) variables .

Therapeutic implications of silent ischemia detection [0039] When assessing the effectiveness of drug therapy on silent ischemia the spontaneous day-to-day variability of ischemic episodes should be taken into account (31). To this aim, performing H-ECG for at least 48 hours in individual patients could be useful to document the reproducibility of the ischemic pattern.

[0040] In patients with variant angina the suppression of episodes of transmural ischemia seems clearly associated with a better outcome (32). Conversely, it is unknown at present whether suppression of silent episodes of subendocardial ischemia by drug therapy improves prognosis in stable and unstable CAD patients. Some attempts to clarify this point have been done in patients with stable CAD.

[0041] In the Atenolol Silent Ischemia Study (33), 306 stable patients with transient ischemia on 48-hour H-ECG were randomized to atenolol or placebo. After 4 weeks, ischemic episodes were present in 61% of patients treated with placebo and in 40% of those treated with atenolol (p=0.002). Total cardiac events at 1-year follow-up occurred less frequently in the group treated with atenolol (11% vs 25%, p<0.001). The absence of ischemia on H-ECG performed after 4 weeks of treatment (with_ _either_ atenolol or_placebo) was associated _ _ with a lower occurrence of cardiac events (11.2% vs 26.9%, p=0.001) .

[0042] The Asymptomatic Cardiac Ischemia Pilot (ACIP) study (34) was designed to specifically evaluate the feasibility of a trial aimed at assessing the impact of silent ischemia suppression on clinical outcome. In this study, 618 CAD patients who had positive stress test and at least 1 episode of silent ischemia on 48-hour H-ECG were randomised to three strategies of treatment: 1) medical therapy adjusted to suppress angina (angina-guided strategy); 2) medical therapy increased to also suppress silent ischemic episodes (ischemia- guided strategy) ; 3) coronary revascularization (angioplasty or bypass surgery) . At 1-year follow-up, major cardiac events (death or myocardial infarction) occurred in 9.9% of patients in the angina-guided group, in 6.5% of those in the ischemia- guided group and in 2.6% of those in the revascularization group. These differences were significant only for the comparison between groups of revascularization and angina- guided medical therapy (p=0.01) (35). The ACIP study does not provide evidence that suppression of silent ischemia by drug therapy can be associated with improved prognosis. However, ischemia-guided treatment failed to reach a better control of ischemic episodes in this pilot study, as H-ECG at the 1-year follow-up still showed silent ischemia in 64% of patients in the ischemia-guided group versus 69% of patients in the angina-guided group. Ischemic episodes, on the other hand, were suppressed in 57% of patients assigned to revascularization, but it is not clear whether there was any relationship between suppression of ischemia and improved prognosis (35) .

[0043] In the Total Ischemic Burden_^European Trial (36) , _ 537 patients with stable angina and positive exercise test were randomized to atenolol, nifedipine or their combination. The occurrence of ischemia and of cardiac events were similar among the three groups and no relationship was also found between presence of ischemia and cardiac events. Indeed, at 2-year follow-up, major cardiac events occurred in 11% of patients with, and in 9.5% of those without ischemia at H-ECG performed after 6 weeks of treatment.

[0044] In the TIBBS study (28), however, among 283 CAD patients, total cardiac events occurred in 32.3% of patients with, and in 17.5% of patients without, ischemia at follow up (p=0.008). There was no difference in the occurrence of major cardiac events, however (11.3% vs 7.2%, p=0.28).

[0045] Overall, these results are controversial and only a well designed future study can answer the question whether suppression of silent ischemia is associated with a better clinical outcome.

Management

[0046] Drugs that are effective in preventing episodes of symptomatic ischemia (nitrates, calcium antagonists, and beta blockers) are also effective in reducing or eliminating episodes of silent ischemia. In the Atenolol Silent Ischemia Study Trial (ASIST) , 4 weeks of atenolol therapy decreased the number of ischemic episodes detected on ambulatory ECG (from 3.6 to 1.7; p = 0.001) and also the average duration (from 30 to 16.4 minutes per 48 hours; p = 0.001) (33).

[0047] Although suppression of ischemia in patients with asymptomatic ischemia is a worthwhile objective, whether treatment should be guided by symptoms or by ischemia as reflected by the ambulatory ECG has not been established. The ACIP Pilot Study showed_that the proportion _o_.f patients free of ischemia on a 48-hour ambulatory ECG among medically treated patients assigned to an "ischemia-guided" strategy and those assigned to an "angina-guided" strategy was 31 and 36 percent, respectively, at 1 year (p = NS) . Among patients treated with coronary revascularization, 57 percent were free of ischemia at 1 year (p = 0.001). Similar trends were noted in the results of exercise testing (37) .

[0048] Coronary revascularization is superior to medical therapy for the relief of both angina and ambulatory ischemia at 12 weeks (37) . Moreover, the early benefits of revascularization on ischemia are associated with improved clinical outcomes. In this pilot study with over 2 years of follow-up, total mortality was 6.6 percent with the angina- guided strategy, 4.4 percent with the ischemia-guided strategy, and 1.1 percent with the revascularization strategy (p = 0.02). The rate of death or myocardial infarction was

12.1 percent in the angina-guided strategy, 8.8 percent in the ischemia-guided strategy, and 4.7 percent in the revascularization strategy, and a strong reduction was also seen in recurrent hospitalizations and the revascularization strategies. These differences were significant, but no differences were noted between the two strategies of medical therapy.

[0049] Whether the incremental prognostic information provided by adding an ambulatory ECG to a standard stress test will justify the cost of using this modality as a tool for widespread screening remains to be determined. Exercise ECG can identify the majority of patients likely to have significant ischemia during their daily activities and remains the most important screening test for significant CAD. Many patients with type I silent ischemia have been identified .because of _an asymptomatic .positive exercise ECG obtained following myocardial infarction. In such patients with a defective anginal warning system, it is reasonable to assume that asymptomatic ischemia has a significance similar to that of symptomatic ischemia and that their management with respect to coronary angiography and revascularization should be similar. As such, myocardial ischemia, as opposed to symptoms alone, has been identified as a valid therapeutic target.

[0050] The value of ambulatory monitoring for quantitative evaluation of the ischemic patient is hindered by its poor reproducibility and technical difficulties that have not yet been completely overcome. Although ambulatory monitoring does provide meaningful information about ischemia in IHD patients, as a potential test for those who are unable to exercise, it can detect Prinzmetal' s variant angina and hidden arrhythmias and assess the effectiveness of antiarrhythmic therapy.

Because ambulatory monitoring does not appear to be useful for screening or for primary detection of IHD in asymptomatic patients, exercise testing remains the most important screening test for IHD.

BRIEF SUMMARY OF THE INVENTION [0051] The present invention provides novel devices for monitoring physiological conditions of the type described above on a long term basis without interfering with the normal activities of the individual. Each such device comprises: a monitoring unit composed of at least one electrode constructed to be placed in contact with the skin of the individual to produce a signal corresponding to the physiological condition, an amplifier coupled to the electrode to amplify the signal produced by the electrode, and a signal jpr cessing unit coupled to _.the amplifier to proce_s_s the amplified signal from the amplifier in order to derive an indication of the physiological condition; and attachment means for securing the unit to the skin of the individual at a selected location with the electrode in contact with the skin.

[0052] The configuration and programming, of the signal processing unit can be in accordance with principles already known in the art and can use software already known in the art for processing heartbeat pattern signals in order to obtain the desired physiological condition indications.

[0053] Devices according to the invention will be useful for monitoring patients with known heart disease including ischemic heart disease and various disorders of cardiac rhythm. For example, the devices will provide an easy way for detecting the occurrence and frequency of episodes of myocardial ischemia or arrhythmias. The devices can also be used for evaluation and diagnosis of patients without known heart disease, for example, people who are at risk for coronary disease or those complaining of palpitations who are suspected of having an arrhythmia. Another useful application of the devices is to monitor the efficacy of medical therapy for myocardial silent ischemia or hypertension. In research- oriented models, other capabilities such as heart rate variability and circadian rhythms analysis will be included. [0054] Devices according to the invention can be worn on the wrist or can be adhered to other parts of the body. For example can be in the form of a patch that is adhered to the skin at a selected point on the chest for detections of myocardial silent ischemia and infraction. The devices can also be of the size of a regular wristwatch to be worn on the wrist._ A _ device, worn on the. wrist can „ record_ and _^analyze _ECG_ data and transfer the resulting information via the Internet, telemedicine programs or other method to the physician. The devices can be used to detect both changes in heart rhythm (arrhythmias) and silent myocardial ischemia manifesting as ST-segment changes. Additionally, blood pressure can be monitored on a continuous basis.

[0055] While data accumulation is continuous, data analysis will result in collecting and storing only clinically significant events (programmable) , giving the physician enough information to treat the patient appropriately. The patient will be able to activate an event marker (e.g. when chest pain or palpitations are experienced) to allow comparison between subjective symptoms and concomitant ECG recording. The device can also have an "alarm" option. If the device detects a life-threatening abnormality such as severe ischemia or a serious arrhythmia, it will signal the patient to seek medical attention. The device can interact with an Internet-based telemedicine network. This feature will give physicians quick access to data relevant to the care of their patients from anywhere with Internet access (including portable computers and palm pilot) as well as a convenient data storage.

[0056] Telemedicine is the most advantageous way to create a data base center to transfer patient's history files to a doctor. There are two advantages on this way of work, first, for the patient, he can see his medical history file anywhere in the world and can send this information to any doctor in the world to get a second or third opinion. The patient now can decide what doctor he would like to see. For the doctor, this network will give the option to see patients everywhere, to explore the number of patient, to work in a why that will give feedback on the treatment without having to see the jpatient. _ There_are _.economic aspects to this_ way pf_working,_ for example fewer office visits and less money to pay. In case of a preventive treatment, continuous feedback meaning less expensive operations and treatment.

[0057] A telemedicine network can employ a server as the center of information coupled to users via the internet. Each user can have an ID and password and each doctor can have a Doctor ID and password. Each user will buy and use a device according to the invention. The device will transmit information to the center by wireless, or LAN, or a combination thereof. The way of initialization the connection to the center can be manual, automatic or semiautomatic. In case of an emergency detected by a device, the center will send an e-mail or beeper message or other type of signal to the doctor. The doctor will log in to his patient file and wil] give his opinion for treatment or other instructions. [0058] One possible working procedure is the following: A device will operate at times selected by the user or automatically or at the first communication opportunity, with any connection method and the information will download to the center. At the center the information will be written into a personal file for storage. The doctor will log onto the patient file and review the information. The doctor can then send a message to the patient to contact him or an e-mail with instruction or an e-mail to the center and the center automatically will call or peep to the patient. The user can access his file and look at the information or send an e-mail with the information to another doctor, and can expose or give a partial or complete access to his file to the other doctor. [0059] Patients with silent ischemia have been stratified into three categories. Type I silent ischemia occurs in totally asymptomatic patients with obstructive CAD, which may be severe_.. _ S_ me_ type Ijpatients do not even experience jρair\ in the course of myocardial infarction. Type II silent ischemia occurs in patients with documented previous myocardial infarction. Type III silent ischemia occurs in patients with the usual forms of chronic stable angina.

[0060] When monitored, patients with this form of silent ischemia exhibit some episodes of ischemia that are associated with chest discomfort and other episodes that are not—i.e., episodes of silent (asymptomatic) ischemia. The "total ischemic burden" in these patients refers to the total period of ischemia, both symptomatic and asymptomatic. Episodes of myocardial ischemia, regardless of whether they are symptomatic or asymptomatic, are of prognostic importance. In particular, silent ischemia is associated with an adverse cardiac outcome if the episodes are frequent or accelerating. Importantly, effective treatment of silent ischemia with medical therapy or revascularization is associated with a substantial reduction in coronary events. Therefor, a simple tool for silent ischemia detection is highly desirable.

[0061] Thus, a device according to the invention can be worn on the wrist and will detect cardiac problems, such as silent ischemia and infraction, etc. Then, the information generated in the device can be downloaded to a PC or sent to the physician via telemedicine program, e-mail or other methods. In cases of emergency an alarm will be heard.

[0062] A device according to the invention in the form of a skin patch will detect the same conditions as the wrist device. In the skin-patch device, the electronic circuitry will be in the patch and thus directly on the chest. The patient will periodically download the information generated in the device to a logger. The information will be transferred to the physician via a telemedicine provider.

[0063J Devices_, according to the invention _.can perform one or more of the following: continuous ECG monitoring, with myocardial silent ischemia & infraction detection based on ST- segment changes; arrhythmia detection; blood pressure monitoring; heart rate variability monitoring; circadian rhythm monitoring. [0064] These devices can perform: Self initiation data saving; Patient-activated event marking (e.g. when chest pain or palpitations are experienced) ; Manual operation at any time; Data recording and analysis; Auto alarm if the system detects a life-threatening abnormality such as severe ischemia or a serious arrhythmia; Telemedicine or other methods for data downloading.

[0065] In the telemedicine approach, the devices will interact with an Internet-based telemedicine network, allowing quick access for physicians to data relevant to the care of their patients from anywhere with Internet access (including portable computers and palm pilot) , easy data sharing between physicians; and convenient and cheap data storage.

[0066] Devices according to the invention are characterized by small-size, in the case of the wrist device, a high level of comfort and confidence to the patient, continuous operation; and detection of silent ischemia on a continuous basis. When used with the telemedicine approach, the devices provide feedback for the physician regarding the efficacy of treatment . [0067] Devices according to the invention will be useful for monitoring patients with known heart disease including ischemic heart disease and various disorders of cardiac rhythm. For example, the devices will provide an easy way for detecting the occurrence and frequency of episodes of myocardial ischemia or arrhythmias. The devices can also be _ _used for evaluation and diagnosis of patients without. known heart disease. For example, people who are at risk for coronary disease or those complaining of palpitations who are suspected of having an arrhythmia. Another useful application of the devices is to monitor the efficacy of medical therapy for myocardial silent ischemia or hypertension [0068] The devices will record ECG data and will detect mainly: deviation in ST segment; duration of the QRS complex; abnormalities of the T wave; changes in Heart Rhythm (HR) ; and, optionally changes in blood pressure detections. The device can perform continuous ECG monitoring. Data can be accumulated and processed continuously to produce physiology information and data analysis to give the doctor enough information to give appropriate treatment to the patient.

[0069] When a device according to the present invention used to monitor blood pressure, it can be associated with a unit for injecting a blood pressure medication into the patient under control of the blood pressure reading, allowing injecting of the minimum required dose of medication. The same procedure can be used if the devices employed to monitor the blood sugar level of a diabetic patient.

BRIEF DESCRIPTION OF THE DRAWING [0070] Figure 1 is a perspective, partly exploded, view of a first embodiment of a monitoring device according to the present invention. [0071] Figures 2 and 3 are perspective views illustrating electrode 12 of Figure 1 in greater detail.

[0072] Figure 4 is a cross-sectional view illustrating one electrode element 32 to a larger scale than Figure 3.

[0073] Figure 5 is a perspective view of a second electrode assembly, viewed from the side at which the electrode assembly will contact the skin. [0074] Figure 6 is a perspective view of the assembly of Figure 5, viewed from the opposite side.

[0075] Figure 7 is a circuit diagram of one embodiment of an amplifier that can be used in a device according to the present invention.

[0076] Figure 8 is diagram illustrating an exemplary transfer function of the circuit of figure 7.

[0077] Figure 9 is a flow diagram illustrating the operation of the device according to the invention. [0078] Figure 10 is an elevational, cross-sectional view, taken along line A-A of figure 11, of a second embodiment of a monitoring device according to the present invention.

[0079] Figure 11 is a top plan view of the embodiment of Figure 10. [0080] Figure 12 is a perspective view of the embodiment shown in Figures 10 and 11.

DETAILED DESCRIPTION OF THE INVENTION [0081] Figure 1 is a perspective, partly exploded, view of a first embodiment of a monitoring device according to the present invention. This device includes a monitoring unit composed of an electrode 12 connected to an electronic unit 14. Electrode 12 and unit 14 are installed in a housing 16. [0082] Electronic unit 14 contains an amplifier, a signal processing unit, a memory and a communication unit that can include a receiver and a transmitter. These components are not illustrated in detail and can be constituted by components that are conventional in the art.

[0083] Housing 16 also contains batteries, operational buttons, including an autodetection button, an event button, a _manual operation button and a timer operation button (not_ shown in Fig. 1) , together with port connections, including one or more of serial ports for applications such as blood pressure monitoring, Sp02, temperature, etc., a printer port, a telephone line connector, an infrared port, a USB port, a port for changing the battery and/or for connection to an external energy source, etc. (none of which are shown in

Figure 1) . Casing 16 further includes a display 18 that can display the time, date, results of the data processing operations, etc.

[0084] All of the components mentioned above can be constructed according to principles already known in the art. [0085] The monitoring unit is associated with elements 22 for attaching the unit to the wrist of an individual whose physiological condition is to be monitored. Elements 22 can take the form of any conventional bracelet, watchband, or other type of wrist band and can be equipped to sense blood pressure, body temperature, etc.

[0086] Figures 2 and 3 are perspective views illustrating electrode 12 of Figure 1 in greater detail. Electrode 12 may be disposable or not. Figure 2 is an exploded view and shows that the electrode is composed of a supporting body 30 made of metal or plastic material and serving as housing for the electronic component. There is a connection to the electrode on the bottom of the device, as shown in Figure 12. Body 30 is provided with a plurality of bores, each of which receives a respective electrode element 32.

[0087] Figure 4 is a cross-sectional view illustrating one electrode element 32 to a larger scale than Figure 3. Element 32 is composed of an elastic body 40 that acts as a spring when the electrode is brought into contact with the skin of the individual and a metal cap 42 that serves as a vacuum cap, or suction cup._ Cap 42 is provided at its outer surface with a recess 44 in which a partial vacuum is created when the electrode is pressed against the user's skin. A wire 46 conductively connects metal cap 42 to an associated amplifier. [0088] Figure 5 is a perspective view of a second electrode assembly, viewed from the side at which the electrode assembly will contact the skin. This electrode assembly is composed of a support board 50 carrying a plurality of electrode elements 52 in the form of very fine, stiff needles measuring l-100μm in diameter and having a length of 0.1-lOmm, and preferably 2- 3mm. Needles 52 are of a size that allows them to penetrate the skin to a depth of possibly 2-3mm in order to establish good electrical contact with the skin without causing injury.

[0089] Figure 6 is a perspective view of the assembly of Figure 5, viewed from the opposite side.

[0090] Figure 7 is a circuit diagram of one embodiment of an amplifier that can be used in a device according to the present invention. The amplifier is shown connected to a hairy or other type of electrode pad 70 that may be made of gold or other conductor material and that is an alternative to the electrodes shown in Figures 2-6. The electrode pad is supported by the device casing in order to lie flat against the skin. The amplifier is based on conventional technology employing two operational amplifiers, including a main amplifier and a feedback amplifier. The feedback loop of the main amplifier includes the feedback amplifier and a capacitor that causes the amplifier to function as an integrator. This arrangement reduces the gain of the amplifier at low frequencies in order to keep the relatively large electrode offset voltages within the dynamic range of a 16 bit analog- digital converter, as indicated by the exemplary transfer function shown in Figure 8. The electronic components of the amplifier may be nqunted at one side:_of _a_ ceramic substrate ^■. __ having a diameter of 5mm, while the other side of the substrate is covered with a printed gold layer forming electrode 70. The amplifier circuitry can then be sealed in a suitable resin, such as an epoxy.

[0091] Electrode 70 and the amplifier together form an active electrode in which the close connection between electrode pad 70 and the input to the first operational amplifier allow a maximum S/N ratio to be achieved. The four conductors at the right-hand side of Figure 7 may be solid pins that will be connected to the main body. This apparatus produces a positive displacement between the electrodes and the main housing.

[0092] The arrangement shown in Figure 7 constitutes an active electrode in that the flat electrode 70 allows the amplifier, or preamplifier, circuitry to be positioned very close to the skin, resulting in a high S/N ratio. The preamplifier may operate according to a locking amplifier method. Using this method gives the option to have a lower signal to noise ratio. The operation of this mechanism is the following: the signal samples are passed through an electronic or mechanical gate that operates at high frequency of 50Hz -

100 GHz. Each sample is a freeze of a positioning collecting a frame of a signal.

[0093] In contrast to prior art systems, the active electrode of Figure 7 performs all analog signal processing, e.g. amplification and DC rejection, at the active electrode and retains the usual configuration of amplifying the biopotential signal with respect to a reference signal.

[0094] Figure 9 is a diagram illustrating the operation and flow of data produced by the data processing unit of a device according to the invention. At point 80 operation is started by activation_of _a_._start_ button _.by the user. This_, causes the signal being received by the device to be recorded at point 82 and to be subjected to immediate and continuous analysis at point 84. The result of the data analysis is saved for a short time at point 86 and permanently at point 88. In addition, the result of the data analysis is applied to point 90 where the result of the data analysis is further analyzed to determine whether the data indicates the existence of a dangerous physiological condition. If such a condition is found to exist, then an emergency alarm is generated at point 92. The data stored at point 88 may then be outputted at point 94 via any suitable communication medium as indicated in figure 9. The data saved at point 86 can be deleted at point 96 at appropriate time intervals. Event recording may be used to record data when the patient feels a chest pain or dizziness or other symptom, in which the patient pushes a button, thereby marking the event (date and time) so the physician will see the ECG and can determine whether the pain that the patient felt was from the heart or had another cause. The event recording will record only events several minutes before the pain and several minutes after. Manual recording can be used when the patient feels pain and wants the physician to examine the event time and its aftermath, or when the physician instructs the patient to record at a specific time and date.

[0095] Other embodiments of the present invention can be in the form of a patch, as shown for example in Figures 10-12, provided with adhesive material 100 that allows the electrode, or electrodes, 102 to be placed in contact with the skin at any point of the body, for example on the chest. The patch further includes a recorder body 104 and a memory card 106. Electrodes 102 can be disposable. The active electrodes have a quick, .positive,displacement connection to _.the device (see_ Figure 12) . [0096] The patch shown in Figures 10 and 11 can be positioned to detect various cardiac conditions, such as myocardial silent ischemia, arrhythmia and infarction. [0097] The foregoing description of the specific embodiments will so fully reveal the general nature of the invention that others can, by applying current knowledge, readily modify and/or adapt for various applications such specific embodiments without undue experimentation and without departing from the generic concept, and, therefore, such adaptations and modifications should and are intended to be comprehended within the meaning and range of equivalents of the disclosed embodiments. It is to be understood that the phraseology or terminology employed herein is for the purpose of description and not of limitation. The means, materials, and steps for carrying out various disclosed functions may take a variety of alternative forms without departing from the invention.

[0098] Thus the expressions "means to..." and "means for...", or any method step language, as may be found in the specification above and/or in the claims below, followed by a functional statement, are intended to define and cover whatever structural, physical, chemical or electrical element or structure, or whatever method step, which may now or in the future exist which carries out the recited function, whether or not precisely equivalent to the embodiment or embodiments disclosed in the specification above, i.e., other means or steps for carrying out the same functions can be used; and it is intended that such expressions be given their broadest interpretation. References

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Claims

CLAIMS What is claimed is:

1. A device for monitoring a physiological condition of an individual, said device comprising: a monitoring unit composed of at least one electrode constructed to be placed in contact with the skin of the individual to produce a signal corresponding to the physiological condition, an amplifier coupled to said electrode to amplify the signal produced by said electrode, and a signal processing unit coupled to said amplifier to process the amplified signal from said amplifier in order to derive an indication of the physiological condition; and attachment means for securing said unit to the skin of the individual at a selected location with said electrode in contact with the skin.

2. The device of claim 1 wherein said amplifier has an input terminal that directly contacts said electrode.

3. The device of claim 1 wherein said electrode comprises a plurality of fine needles that will penetrate the skin.

4. The device of claim 3 wherein each of said needles has a diameter of 1 to lOOμ and a length of 0.1-lOmm.

5. The device of claim 1 wherein said electrode comprises a plurality of conductive elements each configured to create a local vacuum that acts on the skin and produces swelling.

6. The device of claim 1 wherein the physiological condition is one of: silent ischemia; an arrythmia; blood pressure; blood oxygen level; and cardiac ST depression.

7. The device of claim 1 wherein said attachment means comprise elements for attaching said monitoring unit tσ the wrist of the individual.

8. The device of claim 1 wherein said attachment means comprise an adhesive.