Abstract:
The present invention relates to an implantable cardioverter-defibrillator or pacemaker whose standard circuitry is used to trend a physiological cardiac parameter using intra-cardiac impedance measurements. The trend information may be used to predict the onset of a sudden cardiac death (SCD) event. By being able to predict the onset of an SCD event, patients and their physicians may be forewarned of a life-threatening event allowing them to respond accordingly. The trend information may also be used to predict the efficacy of cardiac-related medications, monitor progress of congestive heart failure, detect the occurrence of myocardial infarction, or simply track changes in sympathetic tone.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a continuation of U.S. application Ser. No. 12/887,273, filed on Sep. 21, 2010, now issued as U.S. Pat. No. 8,340,747, which is a continuation of U.S. application Ser. No. 11/470,926, filed on Sep. 7, 2006, now issued as U.S. Pat. No. 7,826,891, which is a continuation of U.S. application Ser. No. 10/603,876, filed on Jun. 25, 2003, now issued as U.S. Pat. No. 7,171,258, which are incorporated herein by reference, and the benefit of priority of each of which are claimed hereby. 
    
    
     FIELD OF INVENTION 
     The present system relates generally to implantable cardioverter-defibrillators and pacemakers and particularly, but not by way of limitation, to such systems being used to trend a physiological parameter using intra-cardiac impedance measurements. 
     BACKGROUND OF THE INVENTION 
     The heart is generally divided into four chambers, the left and right ventricles and the left and right atria. Blood passes from the right atrium into the right ventricle via the tricuspid valve. The atrial chambers and the ventricular chambers undergo a cardiac cycle consisting of one complete sequence of contraction and relaxation of the chambers of the heart. The term systole describes the contraction phase of the cardiac cycle during which the ventricular muscle cells contract to pump blood through the circulatory system. The term diastole describes the relaxation phase during which the ventricular muscle cells relax, causing blood from the atrial chamber to fill the ventricular chamber. After completion of the period of diastolic filling, the systolic phase of a new cardiac cycle is initiated. 
     Through the cardiac cycle, the heart is able to pump blood throughout the circulatory system. Effective pumping of the heart depends upon five basic requirements. First, the contractions of cardiac muscle must occur at regular intervals and be synchronized. Second, the valves separating the chambers of the heart must fully open as blood passes through the chambers. Third, the valves must not leak. Fourth, the contraction of the cardiac muscle must be forceful. Fifth, the ventricles must fill adequately during diastole. 
     When functioning properly, the human heart maintains its own intrinsic rhythm based on physiologically-generated electrical impulses. However, when contractions of the heart are not occurring at regular intervals, or are unsynchronized, the heart is said to be arrhythmic. During an arrhythmia, the heart&#39;s ability to effectively and efficiently pump blood is compromised. Many different types of arrhythmias have been identified. Arrhythmias can occur in either the atria or the ventricles. Arrhythmias may be the result of such conditions as myocardial infarction, cardiomyopathy or carditis. 
     Ventricular fibrillation is an arrhythmia that occurs in the ventricles of the heart. In ventricular fibrillation, various areas of the ventricle contract asynchronously. During ventricular fibrillation the heart fails to pump blood. If not corrected, the failure to pump blood and thereby maintain the circulation can have fatal consequences. 
     Ventricular tachycardia is an arrhythmia that occurs in the ventricular chambers of the heart. Ventricular tachycardias are typified by ventricular rates between 120-250 beats per minute and are caused by electrical or mechanical disturbances within the ventricles of the heart. During ventricular tachycardia, the diastolic filling time is reduced and the ventricular contractions are less synchronized and therefore less effective than normal. If not treated quickly, a ventricular tachycardia could develop into a life-threatening ventricular fibrillation. 
     Supraventricular tachycardias occur in the atria. Examples of these include atrial tachycardias, atrial flutter and atrial fibrillation. During certain supraventricular tachycardias, aberrant cardiac signals from the atria drive the ventricles at a very rapid rate. 
     Sudden cardiac death (SCD) may be a consequence of cardiac rhythm abnormalities occurring in the ventricles or the atria such as ventricular fibrillation, ventricular tachycardia or one of the supraventricular tachycardias. Sudden cardiac death fatally afflicts about 300,000 Americans each year. 
     Patients with chronic heart disease can receive implantable cardiac devices such as pacemakers, implantable cardioverter-defibrillators and HF cardiac resynchronization therapy devices. Implantable cardioverter-defibrillators (ICDs) are used as conventional treatment for patients whose arrhythmic conditions cannot be controlled by medication. These devices provide large shocks to the heart in an attempt to revive a patient from a cardiac rhythm abnormality that may result in an SCD occurrence. At the present there are no firm predictors for SCD within these devices. 
     SUMMARY OF THE INVENTION 
     This document discusses an implantable cardioverter-defibrillator or pacemaker whose standard circuitry is used to trend a physiological cardiac parameter using intra-cardiac impedance measurements. The trend information may be used to predict the onset of an SCD event. By being able to predict the onset of an SCD event, patients and their physicians may be forewarned of a life-threatening event allowing them to respond accordingly. The trend information may also be used to predict the efficacy of cardiac-related medications, monitor progress of congestive heart failure, detect the occurrence of myocardial infarction, or simply track changes in sympathetic tone. 
     In one embodiment of the present invention, a method of predicting sudden cardiac death includes the steps of determining intra-cardiac impedance, deriving a physiologic cardiac parameter from the determined impedance, trending the parameter over spaced time intervals, and predicting the onset of a sudden cardiac death episode. 
     In another embodiment, a system for predicting sudden cardiac death episode includes a device that measures intra-cardiac impedance, a derivation module that derives a physiological cardiac parameter from the measured impedance, and a module that trends the derived parameter over spaced time intervals to create trend data. The system may also include an analyzing module that analyzes the trend data to predict a sudden cardiac death episode. 
     In a further embodiment, a method of trending a cardiac parameter includes the steps of measuring an intra-cardiac impedance, determining a physiologic parameter using the intra-cardiac impedance, and trending the cardiac parameter over time. 
     In a yet further embodiment, a device for trending a physiological cardiac parameter includes an impedance module that measures intra-cardiac impedance, a parameter module that calculates cardiac parameter values using the measured impedance, and a trending module that generates trend data using cardiac parameter values. 
     These and various other features, as well as advantages, which characterize the present invention, will be apparent from a reading of the following detailed description and a review of the drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       In the drawings, which are not necessarily drawn to scale, like numerals describe substantially similar components throughout the several views. Like numerals having different letter suffixes represent different instances of substantially similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document. 
         FIG. 1  is a schematic/block diagram illustrating generally, among other things, one embodiment of portions of an impedance sensor for trending a physiological cardiac parameter and an environment in which it is used. 
         FIG. 2  is a schematic/block diagram illustrating generally, among other things, one embodiment of portions of an impedance sensor for trending a physiological cardiac parameter. 
         FIG. 3  is a schematic/block diagram illustrating generally, among other things, one embodiment of further portions of the measuring module of the impedance sensor of  FIG. 2 . 
         FIG. 4  is a schematic/block diagram illustrating generally, among other things, an embodiment of further portions of the parameter module of the impedance sensor of  FIG. 2 . 
         FIG. 5  is a schematic/block diagram illustrating generally, among other things, an embodiment of further portions of the trending module of the impedance sensor of  FIG. 2 . 
         FIG. 6  is a schematic/block diagram illustrating generally, among other things, an embodiment of further portions of the analyzing module of the impedance sensor of  FIG. 2 . 
         FIG. 7  is a schematic/block diagram illustrating generally, among other things, another embodiment of portions of the impedance sensor. 
     
    
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT 
     In the following detailed description, reference is made to the accompanying drawings which form a part hereof, and in which is shown by way of illustration specific embodiments or examples. These embodiments may be combined, other embodiments may be utilized, and structural, logical and electrical changes may be made without departing from the spirit and scope of the present invention. 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. 
     The present system and methods are described with respect to implantable cardiac rhythm management (CRM) devices, such as pacemakers, cardioverter defibrillators (ICDs), pacer/defibrillators, and multi-chamber and/or multi-site (in a single chamber or multiple chambers) cardiac resynchronization therapy (CRT) devices that utilize standard pacing and defibrillating leads. The software directing operation of such devices may be modified in a way to utilize intra-cardiac impedance measurements collected by the device to generate a physiological cardiac parameter. The device may also be programmed to trend the generated parameter over time. The trend information may represent changes in sympathetic activity of cardiac tissue and thereby be used to track certain physiologic indicators such as, for example, the prediction of a sudden cardiac death (SCD) event, the efficacy of cardiac-related medications being taken by the patient, the detection of a myocardial infarction, or the progress of congestive heart failure in a patient. For example, one trend may show a slow decrease in overall sympathetic activity over time, while another trend may show a sharp drop in sympathetic activity that is sustained for a given period of time, while yet another trend may show spikes of sympathetic activity at certain times during each day that may be related to how the heart is reacting during specific activities. Because certain trends may indicate a specific physiological indicator (as listed above), the system of the present invention may be configured to identify the occurrence of certain physiological indicators from trend information. Such physiologic parameters may be referred to as “predetermined physiological indicators” to the extent that the system may be configured to identify and track one or more specific indicators based on the trend information. 
     Sympathetic activity refers to the level of activation of the autonomic nervous system, specifically the sympathetic nerves that regulate cardiac muscle contraction. Increased sympathetic activity (or tone) is an important contributor to the generation of spontaneous life-threatening arrhythmias and SCD. Changes in sympathetic activity during specific patient activities (such as exercise or sleep) over time may provide important information for the patient and their physician. 
     There are several physiological cardiac parameters that may be generated from intra-cardiac impedance measurements that provide insight into sympathetic activity by inferring their effects on cardiac contractility. Three exemplary parameters are stroke volume, ejection fraction, and pre-ejection period (PEP). “Stroke volume” refers to the volume of blood pumped from a ventricle of the heart in one beat. “Ejection fraction” refers to the ratio of the volume of blood the heart empties during systole to the volume of blood in the heart at the end of diastole expressed as a percentage. “Pre-ejection period” measures the latency between the onset of electromechanical systole, and the onset of left-ventricular ejection. 
     In one example, it is known that PEP shortens when sympathetic activity is increased. This shortened parameter may be measured via intra-cardiac impedance. Therefore, should a patient experience a myocardial infarction (MI), or have already experienced a MI, electrical remodeling will occur in the heart. This remodeling may manifest itself as an increased average sympathetic activity (detected by the shorted PEP values over some time interval), and eventually a life-threatening arrhythmia and possibly even sudden cardiac death. 
     The following is a detailed description of various systems and methods of generating and trending physiological cardiac parameters based on intra-cardiac impedance that are used to track certain physiological indicators.  FIG. 1  is a schematic/block diagram illustrating generally one embodiment of portions of a system  100  of the present invention and an environment in which it is used. In this embodiment, system  100  includes, among other things, an CRM device  105 , which is coupled by leads  110 ,  112 ,  137  to heart  114 . Heart  114  includes four chambers: right atrium  116 , right ventricle  118 , left atrium  120  and left ventricle  122 . Heart  114  also includes a coronary sinus  124 , a vessel that extends from right atrium  116  toward the left ventricular free wall, and which, for the purpose of this document, is considered to include the great cardiac vein and/or tributary vessels. 
     Lead  110  may include an electrode associated with right atrium  116 , such as a tip electrode  126  and/or ring electrode  128 . The electrode is “associated” with the particular heart chamber by inserting it into that heart chamber, by inserting it into a portion of the heart&#39;s vasculature that is close to that heart chamber, by epicardially placing the electrode outside that heart chamber, or by any other techniques of configuring and situating an electrode for sensing signals and/or providing therapy with respect to the heart chamber. 
     Lead  112 , which is introduced into coronary sinus  124  and/or the great cardiac vein or one of its tributaries, includes one or a plurality of electrodes associated with left ventricle  122 , such as tip electrode  130  and/or ring electrode  132 . Lead  137  includes one or a plurality of electrodes associated with the right ventricle, such as tip electrode  138  and/or ring electrode  140 . 
     Device  105  may also include other electrodes, such as housing electrode  134  and/or header electrode  136 , which are useful for, among other things, unipolar sensing of heart signals or unipolar delivery of contraction-evoking stimulations in conjunction with one or more of the electrodes  126 ,  128 ,  130 ,  132 ,  138 ,  140  associated with heart  115 . Electrodes  134  and  136  may be referred to in the art as “can” electrodes, such that electrodes  126 ,  128 ,  130 ,  132 ,  138 ,  140  positioned in the heart may be compared to or communicate with the “can” electrodes. Alternatively, bipolar sensing and/or therapy may be used between electrodes  126  and  128 , between electrodes  130  and  132 , between electrodes  138  and  140 , or between any one of the electrodes  126 ,  128 ,  130 ,  132 ,  138 ,  140  and another closely situated electrode. In practice, any combination of unipolar and bipolar electrodes positioned within the heart may be used, in addition to combining the electrodes positioned within the heart with “can” electrodes to obtain the necessary impedance measures. 
     Device  105  may include several features that may be represented by modules, process steps and components as hereinafter described. For example, device  105  may include a measuring module  142  that is coupled to one or more of the electrodes  126 - 136  for sensing electrical depolarizations and intra-cardiac impedance corresponding with heart chamber contractions. Device  105  may also include a parameter module  144 , a trending module  146 , an analyzing module  148 , and other modules or features relevant to tracking intra-cardiac impedance and trending derived physiologic parameters over time. For example, device  105  may include a transceiver  150  for communication between device  105  and an outside source such as, for example, an external programmer  152 , an external storage device  154 , or an external analyzing module  156 . 
     Referring now to  FIG. 2 , one embodiment of an example system or device  200  for trending a physiological cardiac parameter is provided. System  200  may include a measuring module  210 , a parameter module  230 , a trending module  250 , and in some cases may further include an analyzing module  270 . Modules  210 ,  230 ,  250  and  270  are further described herein with reference to  FIGS. 3-6 . In essence, the measuring module  210  is capable of measuring intra-cardiac impedance values in a patient, the parameter module  230  is capable of calculating or otherwise deriving a physiologic cardiac parameter using the measured impedance values, the trending module  250  is capable of generating trend data using the derived parameter values, and the analyzing module  270  is capable of analyzing trend data to track predetermined physiological indicators. In some embodiments, analyzing module  270  is part of a device including measuring, trending and parameter modules, such as the device  105  shown in  FIG. 1 . In other embodiments, analyzing module  270  may be an external analyzing module, such as module  156  illustrated in  FIG. 1 , that analyzes trend data at a separate location from the device in which the measuring, parameter and trending modules are located. Also, in other embodiments, system  200  may include other modules or components such as a transceiver  150 , a controller (not shown), a signal generator (not shown), etc. if such components or modules are not integrated into the measuring, parameter, trending and analyzing modules. 
       FIG. 3  illustrates several functions and capabilities of measuring module  210  as it relates to trending device  200  of the present invention. Measuring module  210  may be capable of performing such functions as verifying a correct position of a lead within heart  212 , passing current between electrodes of the lead at spaced time intervals  214 , measuring voltage between electrodes of the lead  216 , calculating impedance values from the measured voltage  218 , and storing impedance values  220 . 
     Verifying the correct position of a lead within heart  212  may include verifying that the lead is correctly positioned within a heart chamber, such as chambers  116 - 122  of  FIG. 1  (leads  126  and  128 ), or within a vessel of the heart, such as vessel  124  shown in  FIG. 1  (leads  130  and  132 ). Verification of the correct position of the lead  212  may not be a required function for the measuring module as the position of the lead may be assumed to be correct when an operator of device  200  activates the device to begin measuring. In some cases, however, verification of that the lead is correctly positioned in the heart may be part of the sensing capabilities of measuring module  210 . 
     Passing current to electrodes of the lead at spaced time intervals  214  may include passing current to one or more electrodes of a lead within the heart, or to an electrode positioned within the heart and to a separate electrode position external the heart (step  215  in  FIG. 3 ), such as, for example, electrodes  134 ,  136  shown in  FIG. 1 . The current may be passed to the electrodes of the lead at a constant rate or at spaced time intervals. The frequency in which current is passed to electrodes of the lead may coincide with the voltage measurements being taken between the electrodes of the lead  216 . The voltage measurements may also be taken between the lead electrode and the external electrode  217 . Preferably, current is provided to the electrodes so that voltage measurements can be taken at any desired time or time interval. For example, voltage measurements could be taken only during what would typically be when the patient is sleeping, when the patient is exercising, or any number of combinations of time periods throughout a given day, week, etc. 
     The measured voltage is then used for calculating impedance values  218 . The calculated impedance values may be sent directly to the parameter module  230  shown in  FIG. 4 , stored within device  200 , or may be transferred to an outside source for storage. Storing impedance values  220  may include storing the impedance values into an array or a like format that reflects variables related to the voltage and impedance values. 
     The parameter module  230  may be capable of performing such functions as collecting impedance values  232 , averaging impedance values over set time intervals  234 , calculating parameter values using calculated impedance values  236 , storing calculated parameter values  238 , and transferring calculated parameter values  240  to, for example, an advanced patient management system  242  or to another outside source  244 . 
     Collecting impedance values may include accessing the stored impedance values, for example, from a stored array of impedance values. The impedance values may be averaged over set time intervals prior to being used to calculate parameter values, or may be directly calculated into parameter values. Averaging impedance values over set time intervals  234  may include averaging the impedance values on, for example, a daily basis, a weekly basis, or other desired set time interval. The calculated parameter values may be stored within device  200  for future processing by device  200 , or for future transfer of the parameter values to an outside source. Calculated parameter values may also be directly transferred to a patient management system or to an outside source that may, in other embodiments, perform the trending and analyzing functions of modules  250  and  270 . 
     The trending module  250 , shown in  FIG. 5 , may be capable of performing several functions. For example, trending module  250  may collect parameter values  252 , trend collected parameter values over set time intervals  254 , compare trends at different times  256 , transfer data to a patient management system  258 , transfer data to an outside source  260 , average parameter values over set time intervals  262 , and trend average parameter values over set time intervals  264 . 
     Collecting parameter values  252  may include collecting all parameter values stored by the parameter module  230 , or collecting only certain parameter values at certain time intervals. Trending collected parameter values over a set time interval  254  may coincide with which parameter values are collected. Trending collected parameter values may include determining changes in parameter values over certain time intervals, such as, for example, changes in an average parameter value for each hour during a 24-hour period, for each day during a 7-day week, for each week during a given month, or for each month over the course of a year, etc. A “trend” may be generally defined as a pattern over a period of time, such as, for example, a net increase over time, a gradual, incremental increase over time, a steady value over time, etc. Comparing trends at different times  256  may not be required in all embodiments of trending module  250 . 
     As stated above, averaging parameter values over set time intervals  256  may be used for trending over set time intervals  264 . Thus, either specific parameter values or average parameter values may be compared to obtain trend data. Trend data may be transferred to an advanced patient management system  258  or to another outside source  260  that may be associated with device  200 . 
     The trend data output by trending module  250  may be analyzed in several different ways. For example, trend data may be analyzed by analyzing module  270  that is part of device  200 . In other embodiments, an individual, or some type of analyzing system or module, such as external analyzing module  156  in  FIG. 1 , that is independent of device  200 , may perform analysis of trend data. 
     Analyzing module  270  may be capable of performing several functions such as those shown in  FIG. 6 . For example, analyzing module  270  may collect trend data  272 , compare trend data  274 , detect differences in trend data  276 , and transfer trend data to a patient management system  278 . Analyzing module  270  may also track changes in sympathetic activity  280 , monitor effects of drug regimens  282 , monitor progress of congestive heart failure  284 , detect occurrence of myocardial infarction  286 , predict sudden cardiac death episode  288 , store results  290 , and transfer results to an outside source  292 . The functions of collecting trend data  272 , comparing trend data  274  and detecting differences in trend data  276  may involve further analysis and processing of trend information generated by trending module  250 , the results of which may be transferred, for example, to an advanced patient management system  278  or another outside source  292 . The trend data that is collected, compared, and detected may be used to track certain physiological indicators, such as indicators  280 - 288 . 
     Trend data analyzed by analyzing module  270  may be generally used to track or monitor sympathetic activity (tone)  280 . Changes in sympathetic activity, inferred from trend data may be useful diagnostic information for physicians. For example, the trend data may be used to monitor the effects of a drug or neural stimulation regimen being given a patient to alter sympathetic activity. The trend data may also be used to monitor the progress of congestive heart failure in a patient. Monitoring trend data related to intracardiac impedance could be used instead of R-R interval frequency spectrum (a conventional approach) or to augment such frequency-based sympathetic tone measurements. 
     Trend data may also be useful for detecting the occurrence of myocardial infarction  286 . This type of detection is possible because a myocardial infarction typically triggers electrical remodeling which leads to increased cardiac sympathetic nerve density. Thus, detecting the occurrence of a myocardial infarction may be important because research has indicated that as many as one out of every three myocardial infarctions are considered to be unnoticed by the patient. In addition, myocardial infarction is usually an eventual precursor to sudden cardiac death episode (SCD). 
     A further use of trend data may be in predicting SCD. Changes in sympathetic activity, as may be inferred from certain types of trends in such physiological parameters as described above, may indicate the onset of an SCD. Early recognition by a patient or the patient&#39;s physician of increases of sympathetic activity over time (as indicated by trend data) may provide an opportunity for earlier treatment for the patient. 
     In some embodiments, the analyzing module of system  200  may be able to store results within device  200  for future transmission to an outside source, or may immediately transfer results to an advanced patient management system. Some advanced patient management systems may include an alarm or similar indicator that would alert the patient or the patient&#39;s physician if, for example, a certain threshold value is met. Other patient management systems may be configured to connect to a communications system, such as, for example, a telecommunications system, the Internet via a hard landline or wireless network system, or satellite system to automatically send patient data at spaced time intervals or continuously send data in real time. 
     One example of a method of trending physiologic parameters is shown in  FIG. 7 . Method  300  may include the steps of measuring intracardiac impedance  3   10 , deriving physiologic cardiac parameters  330 , trending derived physiological parameters  350 , and analyzing trend data to track predetermined physiological indicators  370 . Each of steps  310 ,  330 ,  350  and  370  may include steps or functions that coincide with those functions described with reference to modules  210 ,  230 ,  250  and  270 , respectively, and to systems  100  and  200  generally. 
     The functions performed by the system and method discussed above may be performed by a single unitary device, such as an implantable cardiac rhythm management device. The instructions for performing the steps of the method and the functions related to the device discussed above may be stored on a computer readable medium having computer executable instructions. The present invention may also include a computer data signal embodied in a carrier wave readable by a computing system and encoding a computer program of instructions for executing a computer program of instructions for executing a computer program performing the method steps and system functions discussed above. 
     In some instances, various cardiac rhythm management (CRM) devices that are currently sold and marketed may be modified in order to practice the present invention. For example, if a given CRM device includes hardware capable of performing necessary intracardiac impedance measurements, the software of the system may be modified or augmented for software that performs the impedance measuring, parameter deriving, trending and analyzing functions required by the present invention. 
     It is to be understood that the above description is intended to be illustrative, and not restrictive. For example, the above-described embodiments may be used in combination with each other. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the fill scope of equivalents to which such claims are entitled. In the appended claims, the terms “including” and “in which” are used as the plain-English equivalents of the respective terms “comprising” and “wherein.”