Quantifying autonomic tone with thoracic impedance

The disclosure describes techniques for quantifying the autonomic nervous system (ANS) health of a patient with thoracic impedance measurements. Thoracic impedance may be measured utilizing cardiac electrodes and an implantable medical device housing or other electrodes located on or within the patient. Since greater variability in thoracic impedance may indicate better health of the ANS, monitoring impedance changes in a patient may be used to quantify autonomic tone of the ANS, and ultimately, overall patient health. In some examples, thoracic impedance may be measured in response to a change in patient posture for acute monitoring or at predetermined times over several days, weeks, or months for more chronic monitoring of the patient. An implantable medical device may independently analyze the impedance measurements and transmit an alert to the patient or clinician when impedance changes indicate a change in patient health.

TECHNICAL FIELD

The disclosure relates to medical devices and, more particularly, medical devices that measure physiological conditions.

BACKGROUND

Autonomic nervous system (ANS) activity provides basic physiological responses to many activities of a person. For example, instantaneous autonomically mediated responses such as environmental mechanical stimulus may help to prevent a loss of blood pressure to the upper extremities of the person due to a sudden posture change like rising from a supine position. This physiological response is achieved by peripheral vasoconstriction of the lower extremities modulated by the ANS. Decreased function of the ANS can lead to undesirable symptoms and ailments, such as loss of consciousness upon a sudden posture change. In addition, decreased ANS function is associated with a significantly worse prognosis for heart failure patients.

ANS activity, or autonomic tone, further influences sino-atrial (SA) node and atrioventricular (AV) node function. An increase in sympathetic tone can result in an increased heart rate and an increased rate of AV nodal conduction. Conversely, an increase in parasympathetic tone can result in decreased heart rate and an increase in AV nodal conduction time. Due to these heart-related indications of autonomic tone, heart rate and heart rate variability are two diagnostic tools commonly used to obtain information about the state of the ANS. Indeed, decreases in heart rate variability, as well as increases in night heart rate, are known to be associated with an increasing incidence of heart failure. Implantable medical devices, therefore, have been used to measure heart rate and heart rate variability for providing indices of autonomic tone to a clinician.

SUMMARY

In general, the disclosure describes techniques for quantifying the autonomic nervous system (ANS) health of a patient with thoracic impedance measurements. Although heart rate and heart rate variability can be used to determine the ANS health, or autonomic tone, of the patient, the heart rate information is only clinically relevant when the heart rate is being controlled by the activity of the SA node. Thus, heart rate information is unavailable as an indication of autonomic tone if, for example the patient is experiencing an atrial tachyarrhythmia, or if the heart rate is controlled artificially by pacing, e.g., atrial pacing. In some patients, these circumstances can occur for a majority, if not all, of a patient's time. Measuring thoracic impedance allows for autonomic tone monitoring regardless of the patient's cardiac health and during periods of artificial pacing.

Thoracic impedance measurements may refer to, as examples, intrathoracic or transthoracic impedance measurements. Thoracic impedance may be measured between cardiac electrodes and an implantable medical device housing, as one example of intrathoracic impedance measurement, or between any combination of electrodes located on or within the patient's thoracic cavity. The impedance may be measured periodically over several days, weeks, or months for chronic ANS monitoring, in response to a change in patient posture or activity, or some other physiological change, for acute monitoring, or in any other type of monitoring method appropriate for the patient's condition.

Greater variability in thoracic impedance over time may indicate greater autonomic tone and better health of the ANS. Therefore, any changes to this impedance variability can be used to quantify the relative autonomic tone of the patient and indicate to the clinician if heart failure is more or less probable. As examples, the changes in impedance can be measured between day and night impedance, over time in response to various posture changes or the same posture change, or the general impedance variability over time. An implantable medical device may independently analyze these impedance measurements and transmit an alert to the patient or clinician when impedance changes indicate a change in patient health. Alternatively, the implantable medical device may merely transmit stored impedance measurements to an external computing device for clinician analysis and review.

In one example, the disclosure provides a method that includes measuring a plurality of thoracic impedance values of a patient, and generating a value of at least one autonomic parameter based on variation of the plurality of measured thoracic impedance values, the autonomic parameter value indicative of a relative autonomic nervous system (ANS) health of the patient.

In another example, a system comprises a plurality of electrodes, a sensing module that measures a plurality of thoracic impedance values of a patient via the electrodes, and a processor that generates a value of at least one autonomic parameter based on variation of the plurality of measured thoracic impedance values, the autonomic parameter value indicative of a relative autonomic nervous system (ANS) health of the patient.

In another example, a system comprises means for measuring a plurality of thoracic impedance values of a patient, and means for generating a value of at least one autonomic parameter based on variation of the plurality of measured thoracic impedance values, the autonomic parameter value indicative of a relative autonomic nervous system (ANS) health of the patient.

In another example, a computer-readable storage medium comprises instruction that cause a processor to measure a plurality of thoracic impedance values of a patient, and generate a value of at least one autonomic parameter based on the measured thoracic impedance values, the autonomic parameter value indicative of a relative autonomic nervous system (ANS) health of the patient.

DETAILED DESCRIPTION

This disclosure describes techniques and systems for quantifying autonomic tone of a patient with thoracic impedance measurements as an indication of autonomic nervous system (ANS) health. Since changes in autonomic tone can be used to indicate an improving or declining heart failure prognosis, thoracic impedance monitoring can provide valuable information to a clinician during diagnosis or treatment of many diseases and conditions. Further, thoracic impedance measurements may be obtained utilizing an implantable medical device already implanted to treat a cardiac condition of the patient.

Although heart rate and heart rate variability can be used as an indication of autonomic tone, heart rate measurements are only clinically relevant when the heart rate is determined by the activity of the SA node. When heart rate data is unavailable due to atrial tachyarrhythmia, or artificial pacing, a different measurement technique must be used to obtain an indication ANS health. This can be especially problematic in patients that have artificial pacing during most cardiac cycles. Measuring thoracic impedance allows for autonomic tone monitoring regardless of the patient's cardiac health and during periods of cardiac pacing.

Thoracic impedance may be measured in a variety of ways. For example, intrathoracic impedance may be measured between electrodes within the heart and the housing of the implantable medical device located within the thorax. Alternatively, impedance may be measured utilizing any two or more electrodes located on or within the patient's thoracic cavity, e.g., intrathoracic or transthoracic impedance measurements. In some examples, thoracic impedance may be measured using a subcutaneously implanted device, an externally mounted device, or any combination thereof. This impedance may be measured periodically over several days, weeks, or months for chronic ANS monitoring, in response to a change in patient posture or activity for acute monitoring, or in any other type of monitoring method appropriate for the patient's condition.

Greater variability or differences in thoracic impedance over time may indicate greater autonomic tone and better health of the ANS. Therefore, any changes in impedance or impedance variability can be used to quantify the relative autonomic tone of the patient and indicate to the clinician if heart failure is more or less probable. As examples, the difference in impedance can be measured between day and night impedances, over time in response to various posture changes or the same posture change, and the general impedance variability over time. An implantable medical device may independently analyze these impedance measurements and transmit an alert to the patient or clinician when impedance changes indicate a change in patient health. Alternatively, the implantable medical device may merely transmit stored impedance measurements to an external computing device for clinician analysis and review.

This techniques described in this disclosure may provide one or more advantages. For example, measuring thoracic impedance may allow a clinician to monitor autonomic tone in patients with atrial arrhythmia or artificial pacing. Since these patients may be at greater risk of heart failure, obtaining an early indication of declining health may be crucial to adjusting therapy and effectively treating the patient. Moreover, impedance measurements may be obtained with the use of a medical device needed by or already implanted in the patient. As described herein, intrathoracic impedance measurements may be taken between a intra-cardiac electrode and the electrically conductive housing of the implantable medical device, i.e., the pacemaker. In addition, the implantable medical device may issue an alert to the patient or clinician if the impedance measurements indicate that autonomic tone, and overall patient health, is declining.

FIG. 1is a conceptual drawing illustrating an example system10that includes an implantable medical device (IMD)16for delivering therapy to heart12and capable of quantifying autonomic tone. Therapy system10includes IMD16, which is coupled to leads18,20, and22, and external programmer24. IMD16may be, for example, an implantable pacemaker, cardioverter, and/or defibrillator that provides electrical signals to heart12via electrodes coupled to one or more of leads18,20, and22. Patient14is ordinarily, but not necessarily, a human patient.

Although an implantable medical device and delivery of electrical stimulation to heart12are described herein as examples, the techniques for measuring thoracic impedance to quantify autonomic tone be applied using other medical devices and with or without other therapies. In general, the techniques described in this disclosure may be implemented by any medical device, e.g., implantable or external, that includes or is coupled to at least two electrodes to transmit and receive an electrical signal across a portion of the thorax of patient14. As one alternative example, IMD16may be a neurostimulator that delivers electrical stimulation to and/or monitor conditions associated with the brain, spinal cord, or neural tissue of patient16. As a second alternative example, IMD16may be a diagnostic device coupled to two subcutaneous electrodes at different positions in the thorax of patient14that monitors the intrathoracic impedance of patient14, and does not deliver therapy to the patient.

In the example ofFIG. 1, leads18,20,22extend into the heart12of patient16to sense electrical activity of heart12, deliver electrical stimulation to heart12, and/or measure intrathoracic impedance of patient14. In the example shown inFIG. 1, right ventricular (RV) lead18extends through one or more veins (not shown), the superior vena cava (not shown), and right atrium26, and into right ventricle28. Left ventricular (LV) coronary sinus lead20extends through one or more veins, the vena cava, right atrium26, and into the coronary sinus30to a region adjacent to the free wall of left ventricle32of heart12. Right atrial (RA) lead22extends through one or more veins and the vena cava, and into the right atrium26of heart12.

In some examples, therapy system10may additionally or alternatively include one or more leads or lead segments (not shown inFIG. 1) that deploy one or more electrodes within the vena cava or other vein. These electrodes may allow alternative electrical sensing configurations that may provide improved or supplemental sensing in some patients. Furthermore, in some examples, therapy system10may additionally or alternatively include temporary or permanent epicardial or subcutaneous leads, instead of or in addition to transvenous, intracardiac leads18,20and22. Such leads may be used for one or more of cardiac sensing, pacing, cardioversion/defibrillation, and/or thoracic impedance measurement.

IMD16may sense electrical signals attendant to the depolarization and repolarization of heart12via electrodes (not shown inFIG. 1) coupled to at least one of the leads18,20, and22. In some examples, IMD16provides pacing pulses to heart12based on the electrical signals sensed within heart12. The configurations of electrodes used by IMD16for sensing and pacing may be unipolar or bipolar. IMD16may detect arrhythmia of heart12, such as tachycardia or fibrillation of ventricles28and32, and may also provide defibrillation therapy and/or cardioversion therapy via electrodes located on at least one of the leads18,20, and22. In some examples, IMD16may be programmed to deliver a progression of therapies, e.g., pulses with increasing energy levels, until a fibrillation of heart12is stopped. IMD16may detect fibrillation employing one or more fibrillation detection techniques known in the art.

In some examples, programmer24comprises a handheld computing device, computer workstation, or networked computing device. Programmer24may include a user interface that receives input from a user. It should be noted that the user may also interact with programmer24remotely via a networked computing device.

A user, such as a physician, technician, surgeon, electrophysiologist, or other clinician, may interact with programmer24to communicate with IMD16. For example, the user may interact with programmer24to retrieve physiological or diagnostic information from IMD16, such as stored thoracic impedance measurements and/or generated autonomic parameters. A user may also interact with programmer24to program IMD16, e.g., select values for operational therapy parameters of the IMD and configure autonomic diagnostic functions.

For example, the user may use programmer24to retrieve information from IMD16regarding the rhythm of heart12, trends therein over time, or arrhythmic episodes. As another example, the user may use programmer24to retrieve information from IMD16regarding other sensed physiological parameters of patient14, such as intracardiac or intravascular pressure, activity, posture, respiration, or thoracic impedance. As another example, the user may use programmer24to retrieve information from IMD16regarding the performance or integrity of IMD16or other components of system10, such as leads18,20, and22, or a power source of IMD16. In some examples, this information may be presented to the user as an alert. For example, a lead related condition identified based on noise sensed subsequent to delivery of an electrical signal may trigger IMD16to transmit an alert to the user via programmer24. In addition, a sensed decrease in thoracic impedance variability may trigger an alert to programmer24that there may be an increase in heart failure probability.

IMD16and programmer24may communicate via wireless communication using any techniques known in the art. Examples of communication techniques may include, for example, low frequency or radiofrequency (RF) telemetry, but other techniques are also contemplated. In some examples, programmer24may include a programming head that may be placed proximate to the patient's body near the IMD16implant site in order to improve the quality or security of communication between IMD16and programmer24.

FIG. 2is a conceptual drawing illustrating IMD16and leads18,20, and22of system10in greater detail. Leads18,20, and22may be electrically coupled to a signal generator, e.g., stimulation generator, and a sensing module of IMD16via connector block34. In some examples, proximal ends of leads18,20, and22may include electrical contacts that electrically couple to respective electrical contacts within connector block34of IMD16. In addition, in some examples, leads18,20, and22may be mechanically coupled to connector block34with the aid of set screws, connection pins, snap connectors, or another suitable mechanical coupling mechanism.

Each of the leads18,20, and22includes an elongated insulative lead body, which may carry a number of concentric coiled conductors separated from one another by tubular insulative sheaths. Bipolar electrodes40and42are located adjacent to a distal end of lead18in right ventricle28. In addition, bipolar electrodes44and46are located adjacent to a distal end of lead20in coronary sinus30and bipolar electrodes48and50are located adjacent to a distal end of lead22in right atrium26. In the illustrated example, there are no electrodes located in left atrium36. However, other examples may include electrodes in left atrium36.

Electrodes40,44, and48may take the form of ring electrodes, and electrodes42,46, and50may take the form of extendable helix tip electrodes mounted retractably within insulative electrode heads52,54, and56, respectively. In other examples, one or more of electrodes42,46, and50may take the form of small circular electrodes at the tip of a tined lead or other fixation element. Leads18,20, and22also include elongated electrodes62,64, and66, respectively, which may take the form of a coil. Each of the electrodes40,42,44,46,48,50,62,64, and66may be electrically coupled to a respective one of the coiled conductors within the lead body of its associated lead18,20, and22, and thereby coupled to respective ones of the electrical contacts on the proximal end of leads18,20, and22.

In some examples, as illustrated inFIG. 2, IMD16includes one or more housing electrodes, such as housing electrode58, which may be formed integrally with an outer surface of hermetically-sealed housing60of IMD16or otherwise coupled to housing60. In some examples, housing electrode58is defined by an uninsulated portion of an outward facing portion of housing60of IMD16. Other division between insulated and uninsulated portions of housing60may be employed to define two or more housing electrodes. In some examples, housing electrode58comprises substantially all of housing60. As described in further detail with reference toFIG. 4, housing60may enclose a signal generator that generates therapeutic stimulation, such as cardiac pacing pulses and defibrillation shocks, as well as a sensing module for monitoring the rhythm of heart12.

IMD16may sense electrical signals attendant to the depolarization and repolarization of heart12via electrodes40,42,44,46,48,50,62,64, and66. The electrical signals are conducted to IMD16from the electrodes via the respective leads18,20, and22. IMD16may sense such electrical signals via any bipolar combination of electrodes40,42,44,46,48,50,62,64, and66. Furthermore, any of the electrodes40,42,44,46,48,50,62,64, and66may be used for unipolar sensing in combination with housing electrode58. The combination of electrodes used for sensing may be referred to as a sensing configuration.

In some examples, IMD16delivers pacing pulses via bipolar combinations of electrodes40,42,44,46,48, and50to produce depolarization of cardiac tissue of heart12. In other examples, IMD16delivers pacing pulses via any of electrodes40,42,44,46,48, and50in combination with housing electrode58in a unipolar configuration. Furthermore, IMD16may deliver defibrillation pulses to heart12via any combination of elongated electrodes62,64,66, and housing electrode58. Electrodes58,62,64, and66may also be used to deliver cardioversion pulses to heart12. Electrodes62,64, and66may be fabricated from any suitable electrically conductive material, such as, but not limited to, platinum, platinum alloy or other materials known to be usable in implantable defibrillation electrodes. The combination of electrodes used for delivery of stimulation or sensing, their associated conductors and connectors, and any tissue or fluid between the electrodes, may define an electrical path.

The configuration of therapy system10illustrated inFIGS. 1 and 2is merely one example. In other examples, a therapy system may include epicardial leads and/or patch electrodes instead of or in addition to the transvenous leads18,20, and22illustrated inFIG. 1. Further, IMD16need not be implanted within patient14. In examples in which IMD16is not implanted in patient14, IMD16may deliver defibrillation pulses and other therapies to heart12via percutaneous leads that extend through the skin of patient14to a variety of positions within or outside of heart12.

In addition, in other examples, a therapy system may include any suitable number of leads coupled to IMD16, and each of the leads may extend to any location within or proximate to heart12. For example, other examples of therapy systems may include three transvenous leads located as illustrated inFIGS. 1 and 2, and an additional lead located within or proximate to left atrium36. As another example, other therapy systems may include a single lead that extends from IMD16into right atrium26or right ventricle28, or two leads that extend into a respective one of the right ventricle26and right atrium26. An example of this type of therapy system is shown inFIG. 3. Any electrodes located on these additional leads may be used in sensing and/or stimulation configurations.

In the example ofFIG. 2, qualification of autonomic tone may be performed with the components already implanted to treat the heart condition of patient14. IMD16may be configured to measure thoracic impedance, e.g., intrathoracic impedance, of patient14. Thoracic impedance may comprise the electrical resistance (and, in some cases, reactance) across any portion of the thorax of patient14and is an indicator of fluid content within that portion of the thorax. Changes to thoracic impedance are related to acute fluid shifts that occur within the thorax that may be due to acute changes in vascular tone. Since the changes in vascular tone are presumably controlled by and indicative of the relative health of the ANS, measuring the thoracic impedance is an indirect quantification of ANS health. Further, an autonomic parameter may be generated as an index of autonomic tone and improving or declining ANS function from the measured thoracic impedance.

Although a longer electrical path through the thorax may be preferential the path distance between heart12and housing60may be sufficient to identify changes in thoracic impedance. In this manner, the electrical path used to measure thoracic impedance may be between any of electrodes40,42,44,46,48,50,62,64, or66and housing electrode58. By utilizing an electrode already implanted within patient14, autonomic tone may be monitored without any additional surgical procedures.

On example electrical path, or measurement vector, is a bipolar electrode arrangement between elongated electrode62in right ventricle28and housing electrode58. When IMD16is implanted in the thorax close to the clavicle, the measurement vector may detect changes in intrathoracic fluid content indicative of autonomic tone. In other examples, the measurement vector may utilize electrodes40or42of right ventricle28instead of elongated electrode62to obtain the intrathoracic impedance measurement. Alternatively, any of the remaining cardiac electrodes44,46,48,50,64, or66may be configured with housing electrode58to measure the thoracic impedance. Although IMD16is described as implanted in the superior chest region, IMD16may be implanted at any location within or proximate to the thorax of patient14. For example, IMD16may be located in the abdomen of patient14to alter the electrical path between elongated electrode62and housing electrode58.

In another example, a different thoracic electrode may be used in conjunction within housing electrode58. One or more thoracic electrodes may be used instead of a cardiac electrode to measure thoracic impedance. For example, a thoracic electrode may be subcutaneously implanted in the thorax of patient14to be used in a bipolar arrangement with housing electrode58. In addition, a second thoracic electrode may be implanted and used instead of housing electrode58to measure thoracic impedance with the other thoracic electrode. Thoracic electrodes may alternatively be implanted anywhere within the thorax of patient14or even adhered to the external surface of the skin proximate to the thorax. Thoracic electrodes may be electrically coupled to IMD16through a medical lead.

In other examples, thoracic electrodes may be connected to a small implanted module separate from, and in wireless communication with, the IMD. The impedance measuring device may measure thoracic impedance, generate autonomic parameters, and/or transmit the measured impedances or generated autonomic parameters to IMD16. In any case, thoracic impedance may be measured through the operation of IMD16or with a device at least partially independent of IMD16. In some examples, an external device may be coupled to external electrodes, measure thoracic impedance, e.g., transthoracic impedance, and otherwise implement the techniques described herein.

If the electrical path is altered due to the use of an alternative cardiac electrode40,42,44,46,48,50,62,64, or66, the use of a different implanted thoracic electrode, or movement of the IMD16location, it may not be appropriate for new thoracic impedance measurements to be compared to previous measurements or generated autonomic parameters. This change in electrical path may be necessary if an electrode or corresponding medical lead fails to function properly or some other physiological difficulty prevents the use of the previous electrical path. Since the new electrical path may be of a different distance and travel through different organs, autonomic tone may only be monitored using the data from the new electrical path. However, in other embodiments, it may be possible to calibrate the impedance of the old electrical path to the new electrical path. For example, IMD16may be programmed to measure the thoracic impedance of the new electrical path at two different patient14postures and compare these measurements to recently stored measurements from the old electrical path. IMD16may then generate a scaling factor or other formula that can be used to calibrate the old thoracic impedance measurements to new measurements from the new electrical path. In this manner, calibration may allow the clinician to continually use prior autonomic parameters to diagnose and treat patient14.

Additionally, as previously mentioned, IMD16need not deliver therapy to heart12. In general, this disclosure may be applicable to any medical device, e.g., implantable or external, that includes electrodes to sense physiological signals, deliver electrical stimulation to patient14, and/or measure intrathoracic impedance.

FIG. 3is a conceptual diagram illustrating another example of therapy system70, which is similar to therapy system10ofFIGS. 1 and 2, but includes two leads18and22, rather than three leads. Leads18and22are implanted within right ventricle28and right atrium26, respectively. Therapy system70shown inFIG. 3may be useful for providing defibrillation and pacing pulses to heart12. Measurement of thoracic impedance and the generation of autonomic parameters may be performed in two lead systems, such as system70, in the same manner as that described herein with respect to three lead systems. In addition, other thoracic electrodes may also be used to measure the thoracic impedance as described inFIG. 2.

FIG. 4is a functional block diagram illustrating an example configuration of IMD16. In the illustrated example, IMD16includes a processor80, memory82, signal generator84, sensing module86, telemetry module88, posture module89, and power source90. Memory82includes computer-readable instructions that, when executed by processor80, cause IMD16and processor80to perform various functions attributed to IMD16and processor80herein. Memory82may include any volatile, non-volatile, magnetic, optical, or electrical media, such as a random access memory (RAM), read-only memory (ROM), non-volatile RAM (NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory, or any other digital or analog media.

Processor80controls signal generator84to deliver stimulation therapy to heart12according to a selected one or more of therapy programs, which may be stored in memory82. For example, processor80may control stimulation generator84to deliver electrical pulses with the amplitudes, pulse widths, frequency, or electrode polarities specified by the selected one or more therapy programs.

Signal generator84is electrically coupled to electrodes40,42,44,46,48,50,58,62,64, and66, e.g., via conductors of the respective lead18,20, and22, or, in the case of housing electrode58, via an electrical conductor disposed within housing60of IMD16. In the illustrated example, signal generator84is configured to generate and deliver electrical stimulation therapy to heart12. For example, signal generator84may deliver defibrillation shocks to heart12via at least two electrodes58,62,64, and66. Signal generator84may deliver pacing pulses via ring electrodes40,44, and48coupled to leads18,20, and22, respectively, and/or helical electrodes42,46, and50of leads18,20, and22, respectively. In some examples, signal generator84delivers pacing, cardioversion, or defibrillation stimulation in the form of electrical pulses. In other examples, signal generator may deliver one or more of these types of stimulation in the form of other signals, such as sine waves, square waves, or other substantially continuous time signals.

Signal generator84may include a switch module and processor80may use the switch module to select, e.g., via a data/address bus, which of the available electrodes are used to deliver defibrillation pulses or pacing pulses. The switch module may include a switch array, switch matrix, multiplexer, or any other type of switching device suitable to selectively couple stimulation energy to selected electrodes.

Electrical sensing module86monitors signals from at least one of electrodes40,42,44,46,48,50,58,62,64or66in order to monitor electrical activity of heart12. Sensing module86may also include a switch module to select which of the available electrodes are used to sense the heart activity, depending upon which electrode combination is used in the current sensing configuration. In some examples, processor80may select the electrodes that function as sense electrodes, i.e., select the sensing configuration, via the switch module within sensing module86. Processor80may control the functionality of sensing module86by providing signals via a data/address bus.

Sensing module86may include one or more detection channels, each of which may comprise an amplifier. The detection channels may be used to sense the cardiac signals. Some detection channels may detect events, such as R- or P-waves, and provide indications of the occurrences of such events to processor80. One or more other detection channels may provide the signals to an analog-to-digital converter, for processing or analysis by processor80. In response to the signals from processor80, the switch module within sensing module86may couple selected electrodes to selected detection channels.

For example, sensing module86may comprise one or more narrow band channels, each of which may include a narrow band filtered sense-amplifier that compares the detected signal to a threshold. If the filtered and amplified signal is greater than the threshold, the narrow band channel indicates that a certain electrical cardiac event, e.g., depolarization, has occurred. Processor80then uses that detection in measuring frequencies of the sensed events. Different narrow band channels of sensing module86may have distinct functions. For example, some various narrow band channels may be used to sense either atrial or ventricular events.

In one example, at least one narrow band channel may include an R-wave amplifier that receives signals from the sensing configuration of electrodes40and42, which are used for sensing and/or pacing in right ventricle28of heart12. Another narrow band channel may include another R-wave amplifier that receives signals from the sensing configuration of electrodes44and46, which are used for sensing and/or pacing proximate to left ventricle32of heart12. In some examples, the R-wave amplifiers may take the form of an automatic gain controlled amplifier that provides an adjustable sensing threshold as a function of the measured R-wave amplitude of the heart rhythm.

In addition, in some examples, a narrow band channel may include a P-wave amplifier that receives signals from electrodes48and50, which are used for pacing and sensing in right atrium26of heart12. In some examples, the P-wave amplifier may take the form of an automatic gain controlled amplifier that provides an adjustable sensing threshold as a function of the measured P-wave amplitude of the heart rhythm. Examples of R-wave and P-wave amplifiers are described in U.S. Pat. No. 5,117,824 to Keimel et al., which issued on Jun. 2, 1992 and is entitled, “APPARATUS FOR MONITORING ELECTRICAL PHYSIOLOGIC SIGNALS,” and is incorporated herein by reference in its entirety. Other amplifiers may also be used. Furthermore, in some examples, one or more of the sensing channels of sensing module86may be selectively coupled to housing electrode58, or elongated electrodes62,64, or66, with or instead of one or more of electrodes40,42,44,46,48or50, e.g., for unipolar sensing of R-waves or P-waves in any of chambers26,28, or32of heart12.

In some examples, sensing module86includes a wide band channel which may comprise an amplifier with a relatively wider pass band than the R-wave or P-wave amplifiers. Signals from the selected sensing electrodes that are selected for coupling to this wide-band amplifier may be converted to multi-bit digital signals by an analog-to-digital converter (ADC) provided by, for example, sensing module86or processor80. In some examples, processor80may store signals the digitized versions of signals from the wide band channel in memory82as electrograms (EGMs).

In some examples, processor80may employ digital signal analysis techniques to characterize the digitized signals from the wide band channel to, for example detect and classify the patient's heart rhythm. Processor80may detect and classify the patient's heart rhythm by employing any of the numerous signal processing methodologies known in the art.

Processor80may maintain one or more programmable interval counters. If IMD16is configured to generate and deliver pacing pulses to heart12, processor80may maintain programmable counters which control the basic time intervals associated with various modes of pacing, including cardiac resynchronization therapy (CRT) and anti-tachycardia pacing (ATP). In examples in which IMD16is configured to deliver pacing therapy, intervals defined by processor80may include atrial and ventricular pacing escape intervals, refractory periods during which sensed P-waves and R-waves are ineffective to restart timing of the escape intervals, and the pulse widths of the pacing pulses. As another example, processor80may define a blanking period, and provide signals to sensing module86to blank one or more channels, e.g., amplifiers, for a period during and after delivery of electrical stimulation to heart12. The durations of these intervals may be determined by processor80in response to stored data in memory82. Processor80may also determine the amplitude of the cardiac pacing pulses.

Processor80may reset interval counters upon sensing of R-waves and P-waves with detection channels of sensing module86. For pacing, signal generator84may include pacer output circuits that are coupled, e.g., selectively by a switching module, to any combination of electrodes40,42,44,46,48,50,58,62, or66appropriate for delivery of a bipolar or unipolar pacing pulse to one of the chambers of heart12. Processor80may also reset the interval counters upon the generation of pacing pulses by signal generator84, and thereby control the basic timing of cardiac pacing functions, including CRT and ATP.

The value of the count present in the interval counters when reset by sensed R-waves and P-waves may be used by processor80to measure the durations of R-R intervals, P-P intervals, PR intervals and R-P intervals, which are measurements that may be stored in memory82. Processor80may use the count in the interval counters to detect a tachyarrhythmia event, such as ventricular fibrillation or ventricular tachycardia. In some examples, a portion of memory82may be configured as a plurality of recirculating buffers, capable of holding series of measured intervals, which may be analyzed by processor80to determine whether the patient's heart12is presently exhibiting atrial or ventricular tachyarrhythmia.

In some examples, an arrhythmia detection method may include any suitable tachyarrhythmia detection algorithms. In one example, processor80may utilize all or a subset of the rule-based detection methods described in U.S. Pat. No. 5,545,186 to Olson et al., entitled, “PRIORITIZED RULE BASED METHOD AND APPARATUS FOR DIAGNOSIS AND TREATMENT OF ARRHYTHMIAS,” which issued on Aug. 13, 1996, or in U.S. Pat. No. 5,755,736 to Gillberg et al., entitled, “PRIORITIZED RULE BASED METHOD AND APPARATUS FOR DIAGNOSIS AND TREATMENT OF ARRHYTHMIAS,” which issued on May 26, 1998. U.S. Pat. No. 5,545,186 to Olson et al. U.S. Pat. No. 5,755,736 to Gillberg et al. is incorporated herein by reference in their entireties. However, other arrhythmia detection methodologies may also be employed by processor80in other examples.

In some examples, processor80may determine that tachyarrhythmia has occurred by identification of shortened R-R (or P-P) interval lengths. Generally, processor80detects tachycardia when the interval length falls below 220 milliseconds (ms) and fibrillation when the interval length falls below 180 ms. These interval lengths are merely examples, and a user may define the interval lengths as desired, which may then be stored within memory82. This interval length may need to be detected for a certain number of consecutive cycles, for a certain percentage of cycles within a running window, or a running average for a certain number of cardiac cycles, as examples.

Processor80may also control signal generator84and sensing module86to measure the thoracic impedance between two or more electrodes. For example, processor80may cause signal generator84to generate an electrical signal of known current or voltage, and apply the signal to the electrodes. Processor80may control sensing module86to measure a resulting voltage or current, from which processor80may determine an impedance that includes the impedance between the electrodes, i.e., the thoracic impedance. As described herein, an example bipolar electrode combination for measuring the thoracic impedance would be elongated electrode62as the first electrode and housing electrode58as the second electrode. In other examples, processor80may take any alternative approach to impedance measurement known in the art. In some examples, processor80need not calculate impedance, and instead may, for example, monitor variations in measured current or voltage.

The signal generated by signal generator84for impedance measurements may comprise one or more pulses or continuous time signals, e.g., sine waves. The signal may be subthreshold, e.g., below a threshold amplitude and/or pulse width necessary to capture tissue, e.g., the heart. Additionally or alternatively, the signal may be delivered during a period in which the heart is refractory.

IMD16also supports the measurement of thoracic impedance during delivery of therapy to patient14, such as atrial pacing therapy. Processor80may monitor the pacing stimulation generated and delivered by signal generator84to determine the appropriate timing of an thoracic impedance measurement. Preferably, the measurement of thoracic impedance will not interfere with any provided therapy. In some examples, processor80may obtain thoracic impedance values at multiple times during a cardiac cycle in order to get an average impedance value. Alternatively, processor80may time any thoracic impedance measurement to always take place during the same period of the cardiac cycle to minimize the introduction of cardiac function variability into the measured thoracic impedance. In some examples, processor80may use pacing pulses as the signal for impedance measurements, e.g., by controlling sensing module86to measure a voltage or current during delivery of the pacing pulse having a known current or voltage.

The thoracic impedance measurements described herein may be taken using any number of measurement vectors. These vectors may between electrodes within the heart, outside the heart, within the vasculature, or any combination thereof. These vectors may also be between electrodes implanted within patient14, placed on the external skin of patient14, or a combination in implanted and external electrodes. Any of these types of sensing vectors may be used to generate the thoracic impedance measurements. Although the difference of thoracic impedance value is generally described herein, other attributes of impedance such as the phase of the impedance signal may also be used to analyze changes in ANS health.

Processor80may then store the measured thoracic impedance in memory82along with previously measured thoracic impedances. Memory82may store the measured thoracic impedances along with other operational instructions or memory82may include a separate memory for storing the thoracic impedances. If memory82has reached capacity, memory82may replace the oldest stored thoracic impedance with the new thoracic impedance to prevent the discarding of the newest measurement.

In addition, processor80may generate an autonomic parameter based upon the measured thoracic impedance and at least one previously measured thoracic impedance value. This autonomic parameter may be the change in impedance amplitude, the variance in impedance values, the standard deviation of impedance values, the standard error of impedance values, the trend of impedance values (e.g., the magnitude of the slope), the rolling average of impedance values, the maximum change in impedance over a certain period of time, the difference between day impedance and night impedance values, or any other indication of impedance changes. Any and all of these autonomic parameters may also be stored in memory82when generated by processor80.

In chronic monitoring mode, processor80may periodically obtain thoracic impedance measurements to monitor any changes in health of the ANS. The periodic determination may be any regular interval preferred by the clinician. For example, processor80may schedule thoracic impedance measurements every minute, hour, day, or week depending on the condition of patient14. Alternatively, processor80may even obtain the thoracic impedance value multiple times within the same second. Frequent impedance values may be averaged over a period of time to obtain hourly or daily averages, for example. Processor80may alter the measurement of thoracic impedance if therapy changes for any reason. Processor80may compare autonomic parameters to determine of the ANS health is improving, worsening, or staying generally steady.

In an acute monitoring mode, processor80may obtain posture information from posture module89to determine when to obtain or store intrathoracic impedance values. Since the ANS modulates vascular tone, a healthy ANS adjusts vascular tone throughout patient14in order to maintain proper blood pressure at all locations within patient14. Changes in posture or activity may indicate that there already has been or there will be a change to thoracic impedance given sufficient autonomic tone. For example, an orthogonally positioned accelerometer may be configured to detect a sudden change in patient posture and trigger a thoracic impedance measurement. Therefore, processor80may begin measuring and storing thoracic impedance and/or permanently store any impedance measurements obtained and temporarily stored just prior to a change in posture.

In other examples, processor80may additionally or alternatively obtain other physiological information from patient14to determine when to obtain or store thoracic impedance values. For example, processor80may identify changes in heart rate, temperature, or breathing rates, the occurrence of a tachyarrhythmia, or premature ventricular complexes, or any other physiological attribute or event, and obtain and/or store a thoracic impedance measurement in response to the identified attribute or event in the same manner described herein with respect to posture or posture changes. In some examples, IMD16may include other sensors to detect such physiological events or attributes, such as pressure sensors, temperature sensors, or oxygen saturation sensors. Any detected changes in thoracic impedance over time, or temporal changes, may be used by processor80to determine ANS health or other baro-reflex sensitivity.

Posture module89is configured to detect the position of patient14and output a representative signal of the physiological parameter to processor80. Posture module89may be any sensor capable of determining the position or activity level. For example, posture module89may be a single-axis or multi-axis accelerometer, multiple accelerometers, a bonded piezoelectric crystal, a mercury switch, or a gyroscope. A change in posture may include patient14moving from one static position to a different static position or a change in the activity state of patient14. For example, the posture change type may include standing up, sitting up, sitting down, reclining back, laying down, starting to exercise, and stopping exercise. Example activities may include sitting, laying down, walking, running, riding a bike, swimming, driving, or any other activity that the clinician may desire to correlate to autonomic tone.

Posture module89may allow processor80to generate useful information regarding changes in autonomic tone in response to posture changes. For example, processor80may correlate impedance changes to specific posture change types and monitor thoracic impedance variations within that specific posture change type. In this manner, processor80may be able to identify reduced or improved autonomic tone where it may not be discernable when monitoring chronic autonomic tone.

In some examples, processor80may provide an alert to a user, e.g., of programmer24or other computing device, regarding the thoracic impedance measurement or generated autonomic parameter when the condition of patient14has changed. Processor80may compare autonomic parameters to predetermined thresholds and transmit an alert when ANS health has declined below the threshold. In receiving the alert, the clinician can determine if there needs to be a change in stimulation therapy, drug therapy, or any other therapy to treat the decline in ANS health.

Telemetry module88includes any suitable hardware, firmware, software or any combination thereof for communicating with another device, such as programmer24(FIG. 1). Under the control of processor80, telemetry module88may receive downlink telemetry from and send uplink telemetry to programmer24with the aid of an antenna, which may be internal and/or external. Processor80may provide the data to be uplinked to programmer24and the control signals for the telemetry circuit within telemetry module88, e.g., via an address/data bus. In some examples, telemetry module88may provide received data to processor80via a multiplexer.

In some examples, processor80may transmit atrial and ventricular heart signals (e.g., electrocardiogram signals) produced by atrial and ventricular sense amp circuits within sensing module86to programmer24. Programmer24may interrogate IMD16to receive the heart signals. Processor80may store heart signals within memory82, and retrieve stored heart signals from memory82. Processor80may also generate and store marker codes indicative of different cardiac events that sensing module86detects, and transmit the marker codes to programmer24. An example pacemaker with marker-channel capability is described in U.S. Pat. No. 4,374,382 to Markowitz, entitled, “MARKER CHANNEL TELEMETRY SYSTEM FOR A MEDICAL DEVICE,” which issued on Feb. 15, 1983 and is incorporated herein by reference in its entirety.

In addition, processor80may transmit information regarding the measured thoracic impedances or generated autonomic parameters to programmer24via telemetry module88. For example, processor80may provide an alert that the autonomic parameter, e.g., impedance variability, has fallen below a predetermined threshold, suggest that autonomic tone be monitored in a different method, or suggest that electrical stimulation or drug therapy be adjusted in order to compensate for the change in autonomic tone to programmer24via telemetry module88. Processor80may also receive information regarding patient14autonomic tone or responses to such conditions from programmer24via telemetry module88. In addition, processor80may receive intrathoracic impedance data or measurements from other implantable medical devices via telemetry module88.

In some examples, IMD16may signal programmer24to further communicate with and pass the alert through a network such as the Medtronic CareLink® Network developed by Medtronic, Inc., of Minneapolis, Minn., or some other network linking patient14to a clinician.

FIG. 5is functional block diagram illustrating an example configuration of programmer24. As shown inFIG. 5, programmer24may include a processor100, memory102, user interface104, telemetry module106, and power source108. Programmer24may be a dedicated hardware device with dedicated software for programming of IMD16. Alternatively, programmer24may be an off-the-shelf computing device running an application that enables programmer24to program IMD16. In some other examples, programmer24is a computing device capable of receiving thoracic impedances and/or autonomic parameters from IMD16and/or an additional medical device that contributes to impedance measurement.

A user may use programmer24to select values of operational parameters. The clinician may interact with programmer24via user interface104, which may include display to present graphical user interface to a user, and a keypad or another mechanism for receiving input from a user.

The user may also use programmer24to adjust or control the measurement of thoracic impedances and generation of autonomic parameters to quantify the autonomic tone of patient14. Programmer24may also set any instructions that govern the issuance of autonomic tone alerts. For example, the user may use programmer24to determine the frequency of periodic thoracic impedance measurement during chronic monitoring. In another example, the user may use programmer24to select the one or more autonomic parameters used to monitor autonomic tone. If programmer24is a patient programmer, the patient may have limited control over the adjustment of autonomic tone monitoring. However, the patient would still be able to receive alerts on their condition.

Upon receiving an autonomic tone alert from IMD16, programmer24may provide suggestions to the user to remedy the problem. If programmer24is used by the clinician, programmer24may present multiple suggested changes in pacing therapy, drug therapy, or patient lifestyle to limit the effect of declining ANS health. If programmer24is used by patient14, programmer24may suggest a specific posture to remain in, a posture to avoid, and/or to contact their clinician.

User interface104may present thoracic impedances and/or autonomic parameters to the user. This information may be presented numerically, graphically, or both. In addition, the user may select how the information is presented in order to fully understand any changes in ANS health as indicated by the changes in autonomic tone. In this manner, the information presented on user interface104may be interactive and adjustable as the user desires. Examples of graphical information presented on programmer24may include the illustrations of exampleFIGS. 7-9.

Processor100can take the form one or more microprocessors, DSPs, ASICs, FPGAs, programmable logic circuitry, or the like, and the functions attributed to processor100herein may be embodied as hardware, firmware, software or any combination thereof. Memory102may store instructions that cause processor100to provide the functionality ascribed to programmer24herein, and information used by processor100to provide the functionality ascribed to programmer24herein. Memory102may include any fixed or removable magnetic, optical, or electrical media, such as RAM, ROM, CD-ROM, hard or floppy magnetic disks, EEPROM, or the like. Memory102may also include a removable memory portion that may be used to provide memory updates or increases in memory capacities. A removable memory may also allow patient data to be easily transferred to another computing device, or to be removed before programmer24is used to program therapy for another patient.

Programmer24may communicate wirelessly with IMD16, such as using RF communication or proximal inductive interaction. This wireless communication is possible through the use of telemetry module106, which may be coupled to an internal antenna or an external antenna. An external antenna that is coupled to programmer24may correspond to the programming head that may be placed over heart12, as described above with reference toFIG. 1. Telemetry module106may be similar to telemetry module88of IMD16(FIG. 4).

Telemetry module106may also be configured to communicate with another computing device via wireless communication techniques, or direct communication through a wired connection. Examples of local wireless communication techniques that may be employed to facilitate communication between programmer24and another computing device include RF communication according to the 802.11 or Bluetooth specification sets, infrared communication, e.g., according to the IrDA standard, or other standard or proprietary telemetry protocols. In this manner, other external devices may be capable of communicating with programmer24without needing to establish a secure wireless connection. An additional computing device in communication with programmer24may be a networked device such as a server capable of processing information retrieved from IMD16.

In some examples, processor100of programmer24and/or one or more processors of one or more networked computers may perform all or a portion of the techniques described herein with respect to processor80and IMD16. For example, processor100or another processor may receive thoracic impedances or other sensed signals from IMD16for evaluation of autonomic tone.

FIG. 6is a block diagram illustrating an example system that includes an external device, such as a server114, and one or more computing devices120A-120N, that are coupled to the IMD16and programmer24shown inFIG. 1via a network112. In this example, IMD16may use its telemetry module88to communicate with programmer24via a first wireless connection, and to communication with an access point110via a second wireless connection. In the example ofFIG. 6, access point110, programmer24, server114, and computing devices120A-120N are interconnected, and able to communicate with each other, through network112. In some cases, one or more of access point110, programmer24, server114, and computing devices120A-120N may be coupled to network112through one or more wireless connections. IMD16, programmer24, server114, and computing devices120A-120N may each comprise one or more processors, such as one or more microprocessors, DSPs, ASICs, FPGAs, programmable logic circuitry, or the like, that may perform various functions and operations, such as those described herein.

Access point110may comprise a device that connects to network112via any of a variety of connections, such as telephone dial-up, digital subscriber line (DSL), or cable modem connections. In other embodiments, access point110may be coupled to network112through different forms of connections, including wired or wireless connections. In some embodiments, access point200may be co-located with patient14and may comprise one or more programming units and/or computing devices (e.g., one or more monitoring units) that may perform various functions and operations described herein. For example, access point110may include a home-monitoring unit that is co-located with patient14and that may monitor the activity of IMD16. In some embodiments, server114or computing devices120may control or perform any of the various functions or operations described herein, e.g., control performance of thoracic impedance measurements by IMD16or analyze impedance measurements made by IMD16.

In some cases, server114may be configured to provide a secure storage site for archival of thoracic impedances and autonomic parameters that have been collected from IMD16and/or programmer24. Network112may comprise a local area network, wide area network, or global network, such as the Internet. In some cases, programmer24or server114may assemble autonomic parameters or autonomic tone information in web pages or other documents for viewing by and trained professionals, such as clinicians, via viewing terminals associated with computing devices120. The system ofFIG. 6may be implemented, in some aspects, with general network technology and functionality similar to that provided by the Medtronic CareLink® Network developed by Medtronic, Inc., of Minneapolis, Minn.

FIGS. 7A and 7Billustrate example thoracic impedance measurements from Experiment1resulting from posture changes in patient A with a relatively healthy ANS. In the examples ofFIGS. 7A and 7B, the amplitude of changes in intrathoracic impedance values may be the autonomic parameter used as the index of autonomic tone.

As shown inFIG. 7A, graph130provides measured thoracic impedance values over time for the example patient A. Impedance values are provided in Ohms, and generally are between 65 and 85 Ohms. Impedance was measured between the right ventricular defibrillation coil and IMD16housing, i.e., elongated electrode62and housing electrode58, and patient A underwent a variety of posture and activity changes during a ninety minute period. General variation146is a line that indicates the average impedance between the continual variations in beat to beat impedance measurements. The variation in impedance between consecutive measurements is at least partially due to lung volume changes during breathing. Variation due to breathing may be removed by analog or digital smoothing or filtering, e.g., provided by processor80or sensing module86, in some examples.

At time interval132, patient A begins lying in the supine position for 30 minutes and subsequently begins breathing at time interval134. During this period, average line146indicates a gradual decline in thoracic impedance due to increased fluid content in the thorax of patient A. However, impedance begins to increase just before patient A wakes up from a 5 minute sleep at time interval136. General variation146continues to increase until patient A changes posture from the supine position to an upright position by standing up at time interval138. Patient A then sits on a stationary bike at time interval140and begins exercising by pedaling the bike at time interval142. At time interval144, patient A stops pedaling.

General variation146indicates that the thoracic impedance of patient A is changing due to changes in posture, including undertaking different activities. Although the intrathoracic impedance of patient A, as indicated by general variation146, decreases somewhat when patient A is in the supine position between time intervals132and136and when patient A is exercising between time intervals142and144, the largest variations in impedance occur during the relatively brief periods in which patient A changes posture, e.g., standing up from a supine position at time interval138and sitting on a bike at interval140. These changes in thoracic impedance may indicate that the ANS of patient A is capable of regulating thoracic fluid levels in response to, or in anticipation of, changes to posture.

As shown inFIG. 7B, graph150provides a portion of graph130fromFIG. 7A. General variation158indicates the acute change in average thoracic impedance between time intervals136and144ofFIG. 7A. Amplitude156is the measured change in intrathoracic impedances between high value152and low value154. Amplitude156may be used as the autonomic parameter that quantifies the autonomic tone of patient A. Here, amplitude156is approximately 10 Ohms.

Specifically amplitude156may be correlated to the posture change type responsible for the change in thoracic impedance. As shown inFIG. 7A, the large change in impedance was caused by patient A changing from standing to sitting on the stationary bike. For example, posture module89may detect this change in posture and processor80of IMD16may generate the autonomic parameter of amplitude156after measuring the changes in thoracic impedance. In an acute monitoring mode, IMD16may then compare amplitude156to prior amplitudes stored for the same change in posture, or posture change type. A decrease in amplitude may indicate a degradation in autonomic tone and general ANS health, and an increase in heart failure probability. Conversely, an increase in amplitude may indicate an improvement in autonomic tone and ANS health.

In some examples, IMD16may generate further autonomic parameters off of the thoracic impedance values obtained in graphs130and150. IMD16may simultaneously monitor several types of autonomic parameters to best monitor any changes in the health of the patient.

FIG. 8illustrates example thoracic impedance measurements resulting from posture changes in a patient with decreased autonomic tone. As shown inFIG. 8, graph160provides measured thoracic impedance values over time for the example patient B (similar toFIG. 7A). Impedance values are provided in Ohms, and generally are between 65 and 85 Ohms. Impedance was measured between the right ventricular defibrillation coil and IMD16housing, i.e., elongated electrode62and housing electrode58, and patient B underwent a variety of posture and activity changes during a seventy minute period. General variation174is a line that indicates the average impedance between the continual variations in beat to beat impedance measurements. The variation in impedance between consecutive measurements is at least partially due to lung volume changes during breathing.

At time interval162, patient B is resting in a supine posture. At time interval164, patient B moves to a seated posture until patient B stands up at time interval166. Patient B then gets on a stationary bike at time interval168and starts exercising by pedaling the bike at time interval170. At time interval172, patient B stops exercising.

As indicated by general variation174, the thoracic impedance of patient B does not change much in response to posture changes. In fact, the amplitude of the change in general variability174from posture changes, or the autonomic parameter, is essentially zero. In comparison to patient A fromFIGS. 7A and 7B, patient B may have worse autonomic tone due to diminished ANS health. Patient B may be at a higher risk for heart failure. During acute monitoring, further autonomic parameters could be generated from thoracic impedance measurements to determine if the autonomic tone of patient B could increase. In some cases where a patient exhibits minimal changes in impedance amplitude as a result of a few posture change types, e.g., standing up and sitting down inFIG. 8, IMD16may look for other posture change types that have a change in impedance amplitude so that further decreases in autonomic tone could be monitored in a patient like patient B ofFIG. 8.

FIG. 9illustrates an example graph180of impedance variability separated by time of day. As shown inFIG. 9, thoracic impedance has been chronically monitored for patient14. Thoracic impedance has been periodically obtained one or more time per day over a six month period, and IMD16has generated an impedance variability autonomic parameter for the daytime hours (when patient14is awake) and the nighttime hours (when patient14is sleeping) of each day. When these stored autonomic parameters are plotted over time, the result is daytime trend182and nighttime trend184. The difference between daytime trend182and nighttime trend184indicates that the autonomic tone of patient14remains healthy. Since autonomic tone manages thoracic fluid content, little to no difference between awake and sleep intrathoracic impedance measurements may suggest that autonomic tone is diminished. In addition, the increase of both daytime trend182and nighttime trend184over months 4 and 5 may suggest that the ANS health of patient14has been generally decreasing.

In other examples, the difference between daytime variability and nighttime variability may be directly calculated and plotted. Therefore, the graph may show the actual calculated difference between daytime and nighttime thoracic impedance variability. In the case of daytime trend182and daytime trend184, this difference line may be generally flat as there is no change in the difference over time. However, a declining difference between daytime and nighttime measurements may be observed, and an appropriate treatment for patient14could be developed.

Further, the autonomic parameter used to generate graph180and illustrate the difference between day and night thoracic impedances may differ. For example, the autonomic parameter may be a variance, standard deviation, or standard error of the mean graph180may be presented on user interface102of programmer24, on an external computing device120attached to network112ofFIG. 6, a home patient module, or any other display mechanism.

FIG. 10is a flow diagram of an example method of measuring impedance in response to a change in patient14posture. Although described as being performed by IMD16and processor80, the example method may be performed by any device or processor, or combination of devices or processors, described herein.

As shown inFIG. 10, IMD16is engaged in acute monitoring of autonomic tone of patient14. Processor80of IMD16continually monitors patient posture via posture module89(190). Posture module89may detect posture at any predetermined frequency. If processor80identifies a change in posture (192), processor80proceeds to measure the thoracic impedance of patient14(194). If there is no change in posture (192), then processor80continues to monitor posture (190). A change in posture may be identified when the signal from posture module89exceeds a predetermined threshold.

In some examples, processor80initiates impedance measurements, e.g., via signal generator84and sensing module86, upon identification of the change in posture. In other examples, processor80continuously or periodically measures impedance, and selects measured impedances proximate in time to the change in posture, e.g., before and after, for analysis. In such examples, memory82may comprise a buffer for measured impedances.

Once processor80measures the thoracic impedance (194), processor80generates one or more autonomic parameters based upon the measured impedance and at least one previously measured thoracic impedance (196). For example, processor80may determine the amplitude or magnitude between a maximum and minimum of impedance measured proximate to the posture change (e.g., as illustrated inFIG. 7B) as an autonomic parameter. In other examples, processor80may additionally or alternatively determine other values representing the variability of the impedance values proximate the posture change, e.g., statistical measures of variability, such as variability, variance, standard deviation, range, or mean difference. Processor80determines which autonomic parameters to generate based upon instructions set by the user and stored in memory82.

Processor80next stores the impedance measurement and generated autonomic parameters in memory82for later use and review (198). In some examples, values of the autonomic parameter may be available for viewing in the form of a trend diagram, histogram, or the like. Processor80continues to monitor posture (190) if none of the parameters exceed a threshold (200). However, if one of the autonomic parameters exceeds a threshold for the parameter (200), processor80generates an autonomic alert that is transmitted to the user indicating the exceeded autonomic parameter (202). An autonomic parameter exceeds a threshold if the parameter is less than a minimum value, more than a maximum value, or greater than an allowed variation from a threshold. The threshold may be a predetermined value, e.g., selected by a user, a baseline value, e.g., determined based on one or more baseline measurements of the patient's thoracic impedance, or an average of a number of previous measurements.

In some examples, the threshold that processor80compares the newly generated autonomic parameter against may be specific to a particular posture change type. Processor80may identify the posture change type detected by posture module89and compare the resulting autonomic parameters to previously generated autonomic parameters for only the same posture change type. In this manner, autonomic tone is always monitored in the same situation to prevent false negatives and false positives during diagnosis.

In other examples, the method ofFIG. 10may be applied to measure thoracic impedance in response to events other than or in addition to postures changes. For example, processor80may identify changes in activity, heart rate, temperature, or breathing rates or depth, the occurrence of neurological signal or event, gastrological signal or event, a tachyarrhythmia, or a premature ventricular complex, changes in a cardiac or cardiovascular pressure, or any other physiological attribute or event, and obtain and/or store a thoracic impedance measurement in response to the identified attribute or event in the same manner described herein with respect to posture or posture changes. In some examples, IMD16may include other sensors to detect such physiological events or attributes, such as pressure sensors or oxygen saturation sensors. Any detected changes in thoracic impedance over time, or temporal changes, may be used by processor80to determine ANS health or other baro-reflex sensitivity.

FIG. 11is a flow diagram of an example method of chronic intrathoracic impedance monitoring. Although described as being performed by IMD16and processor80, the example method may be performed by any device or processor, or combination of devices or processors, described herein.

In the illustrated example, IMD16continually delivers therapy according to instructions stored in memory82(204). However, in some examples therapy may not be delivered when measuring thoracic impedance, or at all. If processor80determines that thoracic impedance should be measured (206), e.g., a timed schedule indicates that a measurement needs to be obtained, processor80measures the thoracic impedance of patient14(208). Processor80may control the measurement of impedance several times a day, an hour, a minute, or the like. Once the thoracic impedance is measured, processor80stores the measured impedance in memory82for later retrieval and analysis. If stored impedances do not need to be analyzed (212), the processor80continues to deliver therapy (204).

If the stored chronic data needs to be analyzed (212), processor80retrieves the stored impedance data from memory82(214). Processor80then generates autonomic parameters from the stored thoracic impedances so that the user can review the autonomic tone of patient14(216). For example, processor80may generate any of a variety of the variability values discussed above, e.g., daily values based on impedance measurements during a day. Processor80then transmits the autonomic parameters to an external computing device, e.g., programmer24, so that the computing device can present the autonomic parameters as chronic autonomic tone information (218). The autonomic tone information may be presented in many different configurations according to the desires of the user, e.g., as a trend diagram of autonomic parameter values, e.g., a trend of daily thoracic impedance variability values. Processor80then continues to deliver therapy (204).

In alternative examples, all analysis of chronic thoracic impedances may be performed outside of IMD16. Processor80may immediately transmit the stored impedances to the external computing device if the autonomic tone of patient14needs to be analyzed and reviewed (212). Every other analysis step and presentation step is then performed at the external computing device or some other device used to review patient14autonomic tone. On the other hand, processor80may automatically review the presented chronic autonomic tone information and predetermined times and only transmit an alert to the user if the information suggests a decline in autonomic tone.

FIG. 12is a flow diagram of an example method of monitoring autonomic tone with a rolling average of autonomic parameter values. Although described as being performed by IMD16and processor80, the example method may be performed by any device or processor, or combination of devices or processors, described herein.

IMD16continually delivers therapy, e.g., atrial pacing, to patient14according to instructions stored in memory82(220). However, in some examples therapy may not be delivered when measuring thoracic impedance. If processor80determines that thoracic impedance should be measured (222), e.g., a timed schedule indicates that a measurement needs to be obtained, processor80measures the thoracic impedance of patient14(224). Processor80continues to deliver therapy if thoracic impedance does not need to be measured (220).

Various examples have been described. These and other examples are within the scope of the following claims. For example, although the measurement of intrathoracic impedance for ANS monitoring is directed herein toward cardiac therapy, this disclosure may also be applicable to other therapies in which ANS health may be important. These therapies may include spinal cord stimulation, deep brain stimulation, pelvic floor stimulation, gastric stimulation, occipital stimulation, functional electrical stimulation, and any other stimulation therapy utilizing electrode sensing and/or stimulation methods. Furthermore, although described herein as implemented by an IMD and system including an IMD, in other examples, the techniques described herein may be implemented in an external pulse generator. An external pulse generator may be coupled to leads during implant and perform intrathoracic impedance measurements to quantify autonomic tone.

In addition, it should be noted that therapy system10may not be limited to treatment of a human patient. In alternative examples, therapy system10may be implemented in non-human patients, e.g., primates, canines, equines, pigs, and felines. These other animals may undergo clinical or research therapies that my benefit from the subject matter of this disclosure.

The techniques described in this disclosure, including those attributed to IMD16, programmer24, or various constituent components, may be implemented, at least in part, in hardware, software, firmware or any combination thereof. For example, various aspects of the techniques may be implemented within one or more processors, including one or more microprocessors, digital signal processors (DSPs), application specific integrated circuits (ASICs), field programmable gate arrays (FPGAs), or any other equivalent integrated or discrete logic circuitry, as well as any combinations of such components, embodied in programmers, such as physician or patient programmers, stimulators, image processing devices or other devices. The term “processor” or “processing circuitry” may generally refer to any of the foregoing logic circuitry, alone or in combination with other logic circuitry, or any other equivalent circuitry.

When implemented in software, the functionality ascribed to the systems, devices and techniques described in this disclosure may be embodied as instructions on a computer-readable medium such as random access memory (RAM), read-only memory (ROM), non-volatile random access memory (NVRAM), electrically erasable programmable read-only memory (EEPROM), FLASH memory, magnetic data storage media, optical data storage media, or the like. The instructions may be executed to support one or more aspects of the functionality described in this disclosure.