Abstract:
An implantable device monitors the balance between sympathetic tone and parasympathetic tone as a function of an activity level. Cardio-neurological healthy users exhibit a generally sympathetic tone in conjunction with heavy activity level and a generally parasympathetic tone in conjunction with periods of low activity level. Deviations from expected results are associated with a health problem. Measured conditions are stored and available for subsequent reporting to a remote programmer. Therapy delivered by an implantable device is determined as a function of the relationship between autonomic balance and activity level.

Description:
TECHNICAL FIELD 
     This document relates generally to assessing cardio-neurological health and in particular, but not by way of limitation, to an implantable device for assessing health by monitoring autonomic balance while engaged in activities requiring various levels of exercise. 
     BACKGROUND 
     The autonomic nervous system includes a sympathetic component and a parasympathetic (or vagal) component. The sympathetic component is relatively slow acting and is associated with a tendency to raise heart rate, blood pressure, and cardiac output. The parasympathetic component provides a relatively fast response and is associated with a tendency to reduce heart rate, blood pressure, and cardiac output. A proper balance between the sympathetic and parasympathetic components is a characteristic of cardio-neurological health. Variously referred to as autonomic balance, autonomic tone, sympathetic tone or sympathovagal balance, such a metric provides an indication of the patient&#39;s well-being. 
     Autonomic tone is affected by physical activity. In a clinical setting, autonomic tone is measured while the patient engages in a prescribed activity. For example, autonomic tone will increase while a user transitions from a supine position to an upright position. A typical test of autonomic balance, called an orthostatic test, does not adequately provide information as to tone over an extended period of time. 
     SUMMARY 
     One embodiment of the present subject matter provides an implantable cardiac rhythm management device adapted to continuously monitor autonomic tone and physical activity. Patient specific baseline data for a predetermined time, or epoch, is generated and reported. In one embodiment, therapy is tailored according to the current relationship between autonomic tone and activity level and a baseline level. 
     In one embodiment, the baseline data includes data corresponding to a selected population or data corresponding to historical performance of the patient. 
     The present subject matter allows tracking of different levels of stress (as measured by activity) while monitoring autonomic tone. Physiological conditions can be identified by abnormalities in the relationship between autonomic tone and level of activity. In one embodiment, the activity level and autonomic tone are presented over a period of time as a footprint. 
     One embodiment provides sensors tailored to monitor autonomic tone and physical activity level wherein at least one sensor is implanted. Data from the two sensors is correlated by a processor. The processor, in various embodiments, is implanted or externally located. The autonomic tone and physical activity data is available for managing therapy or further analysis. 
     Other aspects of the invention will be apparent on reading the following detailed description of the invention and viewing the drawings that form a part thereof. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the drawings, like numerals describe substantially similar components throughout the several views. Like numerals having different letter suffixes represent different instances of substantially similar components. 
         FIG. 1  illustrates a block diagram of a cardiac rhythm management system according to one embodiment of the present subject matter. 
         FIG. 2  illustrates a block diagram of a cardiac rhythm management system according to one embodiment of the present subject matter. 
         FIG. 3  illustrates a method according to one embodiment of the present subject matter. 
         FIG. 4  illustrates a method according to one embodiment of the present subject matter. 
     
    
    
     DETAILED DESCRIPTION 
     In the following detailed description, reference is made to the accompanying drawings that form a part hereof, and in which is shown, by way of illustration, specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that the embodiments may be combined, or that other embodiments may be utilized and that structural, logical and electrical changes may be made without departing from the scope of the present subject matter. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined by the appended claims and their equivalents. 
       FIG. 1  illustrates a block diagram of system  90 A according to one embodiment of the present subject matter. System  90 A includes implantable unit  100 A and external components. In the figure, implantable unit  100 A includes activity sensor  110 , autonomic tone sensor  120 , internal processor  130 , therapy unit  135 , internal memory  140  and internal telemetry unit  150 . External components include external telemetry unit  200 , remote processing unit  220 , input device  240  and output device  230  and external memory  245 . 
     Implantable unit  100 A includes an implantable housing as well as leads and electrodes adapted to couple with one or more selected organ. In one embodiment, for example, activity sensor  110  includes a minute ventilation sensor and autonomic tone sensor  120  includes a heart rate sensor that provides a signal based on heart rate variability. 
     In various embodiments, activity sensor  110  includes an adaptive rate therapy sensor, examples of which include a minute ventilation sensor, an accelerometer, a respiratory sensor, a QT interval sensor, an impedance sensor, a contractility sensor and a depoloratization sensor. 
     In various embodiments, autonomic tone sensor  120  includes a sensor to provide a signal based on the sympathetic nervous system and the parasympathetic nervous system. Autonomic tone sensor  120 , in various embodiments, includes a heart rate variability sensor, a nerve electrode, a biochemical sensor and a muscle activity sensor. In one embodiment, autonomic tone sensor  120  includes a chemical sensor to monitor a drug level, such as norepinephrine, or a hormone level, such as B-type natriuretic peptide (BNP). B-type natriuretic peptide is a blood borne cardiac hormone that responds to ventricular wall stretch and blood pressure and is associated with symptoms of heart failure. 
     Internal processor  130  includes, in one embodiment, an information processing unit. Internal processor  130  receives an activity signal from activity sensor  110  and a tone signal from autonomic tone sensor  120  and stores a code, or data, in internal memory  140  correlating autonomic tone and physical activity. In one embodiment, internal processor  130  provides an output signal based on the relationship between autonomic tone and physical activity level. Internal processor  130 , in various embodiments, includes a digital processor, such as a microprocessor, or an analog processor. In one embodiment, internal processor  130  executes programming to control the operation of therapy unit  135 . 
     Therapy unit  135 , also coupled to internal processor  130 , includes circuitry and hardware to deliver therapy based on the autonomic tone and physical activity. In one embodiment, therapy unit  135  includes a pulse generator and provides pacing pulses. In one embodiment, therapy unit  135  includes a drug delivery device. 
     Internal telemetry unit  150 , also coupled to internal processor  130 , includes a wireless transceiver for communicating with external telemetry unit  200 , as shown by communication link  160 . In one embodiment, communication link  160  is bidirectional and in another embodiment, communication link  160  is unidirectional. 
     External telemetry unit  200  is coupled to remote processing unit  220  by link  210 . Remote processing unit  220  is also connected to input device  240 , output device  230  and external memory  245 . In one embodiment, external telemetry unit  200 , link  210 , remote processing unit  220 , input device  240 , output device  230  and external memory  245  are housed in a single unit sometimes referred to as a programmer. In one embodiment, the external components are distributed. For example, in one embodiment, link  210  includes a digital communication network. Examples of digital communication networks include a local area network or a wide area network such as the Internet. 
     Remote processing unit  220 , in various embodiments, includes a digital processor, such as a microprocessor, or an analog processor. 
     Input device  240  includes a keyboard, mouse, card reader or other user operable data communication device. Output device  230  includes a display monitor, audio speaker, printer or other device to provide data to an operator. External memory  245 , in various embodiments, includes random access memory (RAM), read only memory (ROM), optical storage medium, magnetic storage medium or other stationary or removable memory medium. 
       FIG. 2  illustrates a block diagram of system  90 B according to one embodiment of the present subject matter. System  90 B includes implantable unit  100 B and external components. In the figure, implantable unit  100 B includes internal sensor  180 , internal processor  130 , therapy unit  135 , internal memory  140  and internal telemetry unit  150 . External components include external telemetry unit  200 , remote processing unit  220 , input device  240 , output device  230 , external memory  245  and external sensor  280 . 
     Internal sensor  180 , in one embodiment, includes an autonomic tone sensor and external sensor  280  includes an activity sensor, each of which are described elsewhere in this document. For example, in one embodiment, internal sensor  180  includes a heart rate variability sensor and external sensor  280  includes an activity monitor coupled to an exercise machine such as a stationary treadmill. External sensor  280 , in various embodiments, is part of an apparatus used for exercising or part of diagnostic equipment in a clinical setting or a health care facility. 
     Internal sensor  180 , in one embodiment, includes an activity sensor and external sensor  280  includes an autonomic tone sensor. For example, in one embodiment, internal sensor  180  includes an accelerometer responsive to physical activity and external sensor  280  includes a heart rate monitor responsive to heart rate variability. 
     Remote processing unit  220  receives an activity signal and an autonomic tone signal from the combination of internal sensor  180  and external sensor  280  and stores data in external memory  245  accessible to remote processing unit  220 . The stored data correlates the autonomic tone and physical activity. Output device  230  is coupled to remote processing unit  220  and provides a visible or audible representation of autonomic tone and physical activity. 
     In one embodiment, remote processing unit  220  executes programming to determine therapy, validate therapy or manage therapy as a function of the autonomic tone and physical activity. For example, following a determination calling for a more rapid pacing rate, a signal from remote processing unit  220  is communicated via link  210  and external telemetry unit  200  to internal telemetry unit  150  for delivery to internal processor  130 . Internal processor  130  then instructs therapy unit  135  to increase the pacing rate. 
       FIG. 3  illustrates method  300  according to one embodiment of the present subject matter. In the figure, a performance baseline for a patient is established. At  310 , an autonomic tone signal is received from an autonomic tone sensor. In various embodiments, the sensor is implantable or externally located. At  320 , an activity signal is received from an activity sensor. The activity sensor, in various embodiments, is implantable or externally located. 
     At  330 , a program executing on a processor operates to separate the autonomic tone data by an activity level as indicated by the activity signal. At  340 , a baseline is established to correlate different activity levels with an autonomic tone. The baseline, in one embodiment, is a compilation of data for a particular user. In one embodiment, the baseline is an aggregate of the data for a particular user and a selected population. The population may be selected on the basis of medical conditions, geographical location or other factors. In one embodiment, the baseline is an evolving metric that begins with seed information derived from a selected population and is tailored with data derived from a particular user. Over a period of time, the population data is attenuated and the comparison data becomes predominantly that of the patient. For example, in one embodiment, the baseline data includes a population norm value for a class IV heart failure event. Other methods to incorporate a population norm as part of a baseline are also contemplated. 
     Consider an exemplary embodiment utilizing an accelerometer for the physical activity component of the baseline. The accelerometer provides an output measured in units of gravity “G” or milli-G. In one embodiment, autonomic tone is measured while the user is engaged in physical activities, including when at a predetermined state of rest, when at a predetermined level of exercise, when transitioning from the predetermined state of rest to the predetermined level of exercise and when recovering, or transitioning, from the predetermined level of exercise to the predetermined state of rest. For each of these conditions, a measure of autonomic tone is generated. In one embodiment, the baseline reflects the patient norms for each of these different conditions. In one embodiment, the baseline reflects a population norm for each of these different conditions. 
     In one embodiment, the baseline for a normal patient can be described, in the frequency spectrum, as transitioning from a supine position to a vertical position. 
     In one embodiment, the baseline is quantized to allow identification and analysis of departures from normal performance. For example, an improving condition may be denoted as a reduced differential between the baseline and a measured condition of autonomic tone and activity level. 
     Using an accelerometer, an activity level can be described by comparing measured accelerations with predetermined acceleration thresholds while engaged in that activity or condition for a predetermined period of time. For example, the user can be described as “at rest” when an acceleration level remains below a particular minimum level for a minimum time period. Discrete acceleration levels may be derived from an average measured acceleration for a window having a predetermined width in time. Filters and other functions may be applied to the acceleration levels to quantify a measured parameter. 
     In one embodiment, the activity level is determined based on a measurement of an autonomic tone. For example, when autonomic tone is measured at a predetermined level, data corresponding to a measured activity level is stored in a memory. Other methods of separating autonomic tone by activity level are also contemplated. 
     In one embodiment, analysis of a trend in data is performed. Trend analysis includes evaluating changes in the patient&#39;s baseline over a period of time. Trends can be evaluated based on comparisons with data from the patient or from a selected population. 
     In one embodiment, a range of activity levels is established for a particular patient. For example, the functional capacity range, which describes the difference between a rest activity level and a highest exertion activity level, is separated into predetermined divisions. In one embodiment, the functional capacity range is quartiled. The range then provides a means for classifying autonomic tone by activity level. 
     In one embodiment, multiple baselines are established for a particular patient. For example, in one embodiment, a resting baseline and a maximum exertion baseline is created at the time of implantation of the present subject matter. After a predetermined period of time, the resting baseline and maximum exertion baseline data are compared with current measurements. 
     In one embodiment, when the relationship between autonomic tone and exertion level (or activity level) indicates an unhealthy or dangerous condition, a warning signal is generated. The warning signal can be provided to the patient, physician or to a monitoring facility. The warning signal provided to a patient may be, for example but not limited to, in the form of a tactile message or audible message and delivered by means of a suitable transducer. The level at which a warning signal is generated, in one embodiment, is selectable by, for example, programming. The warning signal may be tailored to provide notice upon detecting a severely out of balance condition. 
     In one embodiment, a comparison is made between a norm for a selected population and that of a particular patient&#39;s autonomic tone and exertion level. Normative values permit classifying the health of the patient. 
       FIG. 4  illustrates method  400  according to one embodiment. At  410 , autonomic tone data and activity data is received. In addition, baseline information is received at  420 . At  430 , the received autonomic tone data and activity data is compared with the received baseline data. As a function of the comparison, the autonomic tone and activity data is classified, at  440 . For baseline data reflective of a selected population, the classification yields a ranking of the user compared to that population. For baseline data reflective of a particular user, the classification will yield comparative health of the user as compared to that user&#39;s general health. At  450 , the classification information is reported. Reporting, in one embodiment, includes transdermal communication of the data to a remote programmer. 
     Alternative Embodiments 
     A measure of autonomic tone can be derived from heart rate variability. In one embodiment, heart beats are represented by an R-R chart where the horizontal axis corresponds to beats and the vertical axis to time. A spectral analysis of the R-R data reveals content in different frequency bands, including very low frequency components (typically below 0.04 Hz), low frequency components (typically 0.04-0.15 Hz) and high frequency components (typically 0.15-0.4 Hz). A correlation exists between the power spectral density of high frequency band content and the tone of the parasympathetic nervous system and between the power spectral density of low frequency band content and the tone of the sympathetic nervous system. Thus, autonomic tone, according to one embodiment, is a ratio of low frequency signal power to high frequency signal power. 
     In one embodiment, either or both of the activity sensor and autonomic tone sensor includes a sensor configured to chronically or invasively provide data. In one embodiment, the sensor is included in a housing adapted for implantation. In one embodiment, the sensor is coupled by an electrode to a remote housing that is also implanted. 
     In one embodiment, the present subject matter evaluates one or more sensors corresponding to autonomic tone or physical activity. For example, in one embodiment, autonomic tone data is derived from both a heart rate sensor providing a signal corresponding to heart rate variability and a drug level sensor providing a signal corresponding to BNP. As another example, in one embodiment, physical activity data is derived from both a stationary treadmill (or other exercise machine) and an accelerometer. In various embodiments, more than one sensor is used to provide autonomic tone data or physical activity data. 
     In one embodiment, a graphical tool is used to depict autonomic tone data and physical activity data over a period of time. One such tool is an adaptation of a particular histogram sometimes referred to as a footprint. Commonly assigned U.S. Pat. Nos. 6,026,320, 5,603,331, 6,301,499 and 6,529,772 describe footprints and are each incorporated herein by reference. The footprint provides an aggregate picture of autonomic tone (as measured, for example by R-R interval) over a period of time. 
     The footprint, in one embodiment, includes a histogram having a vertical axis corresponding to the absolute value of the difference between adjacent R-R intervals and the horizontal axis corresponding to R-R interval in milliseconds. In one embodiment, the histogram is calibrated in terms of a heart rate with horizontal axis dimensions in milliseconds. The image is a histogram of the occurrence of coded values with each value denoted by the height of the histogram at those locations. During a 24 hour period, for example, all sinus beats are captured and the lowest heart rate achieved appears on the left hand side and the highest rate achieved appears on the right. The difference between the highest and lowest rate corresponds to breadth of heart rate reserve. Increased heart rate variability is indicated by an increased height of the footprint. Greater cardiac reserve is indicated on the footprint by greater width. A mean heart rate is sometimes shown on the footprint with a vertical line. 
     Other periods of time for the footprint are also contemplated. For example, in one embodiment, weekly, monthly or annual average footprint data is compiled. 
     The footprint is adapted to illustrate physical activity data corresponding to the autonomic tone data. Various methods can be used to depict the physical activity level and autonomic tone data. In one method, physical activity data is mapped to a predetermined variable. The footprint images are created continuously and thus, at each activity level, a new image is created. This method provides a histogram having three dimensions where the third dimension represents an activity level. For example, over a 24 hour period, one embodiment of the present subject matter yields a footprint having a melon-shaped region with different slices through the region corresponding to different physical activity levels for the period. In one embodiment, a slice through the left most edge of the region, corresponds to autonomic tones at a low activity level occurring throughout the 24 hour period and a slice through the right most edge of the region corresponds to autonomic tones at a high activity level occurring throughout the 24 hour period. 
     In one method, the footprint is presented as a color coded histogram overlaid atop a grey scale where different colors correspond to different physical activity levels. 
     In one embodiment, an instantaneous physical activity level is compared with autonomic tone. In one embodiment, a processor controlled algorithm is used to determine an activity level. For example, in one embodiment, a time frame is established and a physical activity level is recognized when a sensor reading has stabilized to within a predetermined range of values. In one embodiment, a stable acceleration level, expressed in milli-G&#39;s over a predetermined time period of 30 seconds is associated with a recognized activity level. For each recognized activity level, an autonomic tone metric is also recorded. In one embodiment, an average or minimum duration is taken as a valid reading of physical activity. 
     Other filtering means are also contemplated for capturing valid data and suppressing spurious readings. For example, a minimum acceleration sensor signal level can be established for a minimum duration. In various embodiments, different windows of time are prescribed wherein, for example, a minimum activity for a period of one second, 30 seconds or one minute window is a recognized duration. For example, in one embodiment, an acceleration in the range of 10 to 20 milli-Gs lasting for a duration between 2 and 3 minutes is deemed to be a valid activity level. Other bands of acceleration magnitudes and duration are also contemplated. 
     In one embodiment, a predetermined signal received from a first activity sensor is used to recognize a minimum activity level and a second activity sensor is then correlated with a measured autonomic tone. 
     In one embodiment, a combination of multiple activity sensors are mapped to an activity index. The activity index is correlated with an autonomic tone measurement. 
     In various embodiments, the stored data is available for managing therapy and later analysis. The stored data is available for further analysis by a remotely located processor. In one embodiment, a monitor provides storage for the autonomic tone and physical activity data. 
     In one embodiment, a physical activity sensor is coupled to an exercise machine and an autonomic tone sensor is implanted in a patient. The autonomic tone sensor data is communicated to an external device by a telemetry circuit. A remote processor, coupled by a network connection receives both the physical activity sensor data and the autonomic tone sensor data. The remote processor executes programming to diagnose the received data. In one embodiment, therapy instructions are transmitted from the remote processor, via the network, to an implanted therapy circuit. In one embodiment, an implanted processor receives the data from the physical sensor and performs diagnostic functions, manages therapy and stores data. In various embodiments, the exercise machine includes a treadmill, bicycle, climbing machine, weight lifting or weight moving machine, rowing machine or other exercise equipment. In various embodiments, the signal generated by the exercise machine may correlate to a measure of power, calories, speed, oxygen uptake or other measure of physical activity. The exercise machine may be stationary or mobile. 
     Other combinations are also contemplated. For example, in one embodiment, the physical activity level is measured by an implanted device and an external sensor is used to provide autonomic tone data. As another example, in one embodiment, both the physical activity level and the autonomic tone are measured by an implantable sensor. 
     In one embodiment, each activity level is correlated with autonomic tone. In one embodiment, autonomic tone is correlated with each activity level. 
     CONCLUSION 
     The above description is intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description.