Patent Publication Number: US-8540643-B1

Title: Method and device for motion and noise immunity in hemodynamic measurement

Description:
PRIORITY CLAIM 
     This application is a Divisional of U.S. patent application Ser. No. 10/872,165, filed Jun. 17, 2004, which is entitled “METHOD AND DEVICE FOR MOTION AND NOISE IMMUNITY IN HEMODYNAMIC MEASUREMENT.” 
    
    
     BACKGROUND OF THE INVENTION 
     1. Field of the Invention 
     The present invention relates generally to implantable cardiac devices and, more particularly, to implantable cardiac devices capable of hemodynamic measurement. 
     2. Background Art 
     An implantable cardiac device is a medical device that is implanted in a patient to monitor electrical activity of the heart and to deliver appropriate electrical and/or drug therapy, as required. Implantable cardiac devices include, for example, pacemakers, cardioverters and defibrillators. The term “implantable cardioverter defibrillator” or simply “ICD” is used herein to refer to any implantable cardiac device capable of delivering therapy to prevent or terminate a fast heart rate or a tachycardia. An ICD employs a battery to power its internal circuitry and to generate electrical therapy. The electrical therapy can include, for example, pacing pulses, cardioverting pulses and/or defibrillator pulses. This is in contrast to a “pacemaker” which is an implantable device specifically intended to treat slow heart rates or bradycardia. However, an ICD provides all the features of a pacemaker. An ICD also includes electrical sensing in its circuitry that monitors the electrical activity of the heart. While performing hemodynamic measurements would be advantageous, at present commercially available ICDs do not perform this function. 
     Hemodynamic status describes whether the heart is pumping blood sufficiently to ensure adequate perfusion of vital organs. Delivering anti-arrhythmia therapy, via an ICD for example, according to hemodynamic status of an arrhythmia provides several important benefits. Hemodynamically unstable arrhythmias are treated quickly and aggressively, which improves the chance of successful arrhythmia termination. Hemodynamically stable rhythms, during which the patient is most likely to be conscious, are treated with lower voltage therapies. This approach minimizes the risk of painful shocks and conserves battery power of an ICD while at the same time increases the probability of successful arrhythmia termination. Treating a patient according to hemodynamic status measurement may become even more important as the clinical indications for ICD implant become broader. 
     Hemodynamic status can be measured, for example, by one or more physiologic sensors located within an ICD. One example of a physiologic sensor used for hemodynamic measurement is a hemodynamic sensor. An example of a hemodynamic sensor is an acoustic sensor, which uses an acoustic transducer responsive to heart sounds to detect the hemodynamic status of a patient. For a more detailed description of hemodynamic measurement, including the use of acoustic sensors, see U.S. Pat. No. 6,477,406 B1 (Turcott), which is incorporated herein by reference. Another example of a hemodynamic sensor is a photoplethysmography sensor, such as that described in U.S. Pat. No. 6,409,675 (Turcott), which is incorporated herein by reference. Other types of hemodynamic sensors include intravenous or intracavitory pressure and flow sensors, or optical or mechanical plethysmography sensors. Right ventricular (RV) pressure, for example, is described further in U.S. Pat. Nos. 3,614,954 (Mirowski et al.); 3,942,536 (Mirowski et al.); 4,774,950 (Cohen); 4,967,749 (Cohen); 5,899,927 (Ecker et al.); 6,208,900 (Ecker et al.); 6,221,024 (Miesel); and 6,264,611 (Ishikawa et al.), which are incorporated herein by reference. 
     Conventional approaches to hemodynamic sensing face a common problem in that it is difficult to provide accurate and reliable data in the face of mechanical artifact. For example, hemodynamic status is particularly difficult to measure due to motion-induced artifact associated with a change of posture and chest compressions that are likely to accompany a significant arrhythmia. Other sources of noise that may affect hemodynamic measurement, depending on the type of hemodynamic sensor used, include electrical noise, external light, changes in atmospheric pressure, and radiated energy. 
     What is needed is a device, such as an ICD, that is immune from motion and noise during hemodynamic measurement and can reliably use such hemodynamic measurement to deliver an appropriate electrical therapy. 
     BRIEF SUMMARY OF THE INVENTION 
     The following invention is a method and device that minimize the deleterious effect of noise on hemodynamic sensing algorithms. The present invention is effective for any kind of noise. The source of the noise can include, for example, mechanical artifact associated with motion or change in posture, electrical noise such as thermal and flicker noise, environmental nose such as changes in atmospheric pressure or radiant energy, or any other process or cause that corrupts the measured signal. Conventional ICDs and related signal processing techniques do not resolve this problem. It is important to note that applications of the invention are not limited to hemodynamic assessment, but may be applied to the assessment of any signal. When used during hemodynamic assessment, however, applications of the technique are not limited to hemodynamic assessment during arrhythmia detection. Rather, the technique can be used in any context that requires hemodynamic measurement, such as atrio-ventricular/ventricular-ventricular (AV/VV) optimization, disease monitoring, orthostatic hypotension detection, and therapy, for example. 
     A method and device, such as an implantable cardiac device, for motion and noise immunity in hemodynamic measurement is presented. According to embodiments of the invention, the method includes obtaining a template waveform representing hemodynamic performance of a heart during a first hemodynamic state and obtaining an autocharacterization measure from an autocharacterization (e.g., autocorrelation) of the template waveform. The method further includes obtaining a test waveform during a second hemodynamic state, performing a cross-characterization (e.g., cross-correlation) of the template waveform and test waveform to identify a cross-characterization measure, and comparing the autocharacterization measure with the cross-characterization measure as a measurement of hemodynamic status of the second hemodynamic state. According to embodiments of the invention, the device includes hardware and/or software for performing the described method. A method and device for selecting an appropriate anti-arrhythmia therapy for a patient according to the patient&#39;s hemodynamic status are also disclosed. 
     Further features and advantages of the invention as well as the structure and operation of various embodiments of the invention are described in detail below with reference to the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS/FIGURES 
       The accompanying drawings, which are incorporated herein and form part of the specification, illustrate the invention and, together with the description, further serve to explain the principles of the invention and to enable a person skilled in the relevant art(s) to make and use the invention. In the drawings, like reference numbers indicate identical or functionally similar elements. Additionally, in most drawings, the leftmost digit of a reference number identifies the drawing in which the reference number first appears. 
         FIG. 1A  is a simplified diagram illustrating an exemplary ICD in electrical communication with at least three leads implanted into a patient&#39;s heart for delivering multi-chamber stimulation and shock therapy. 
         FIG. 1B  is a functional block diagram of an exemplary ICD, which can provide cardioversion, defibrillation and pacing stimulation in four chambers of a heart. 
         FIG. 2  illustrates a graphical output of a hemodynamic sensor, as signal amplitude versus time, that represents an exemplary template waveform for a hemodynamic sensor as used in embodiments of the invention. 
         FIG. 3  illustrates a series of sample test waveforms with varying levels of white Gaussian noise, as used in embodiments of the invention. 
         FIG. 4  illustrates a graphical representation of the sensitivity and specificity of both a conventional amplitude analysis and the cross-correlation analysis of the invention, plotted as functions of noise level. 
         FIG. 5  is a flowchart illustrating an embodiment of a method of the invention in which a hemodynamic performance of a patient&#39;s heart is measured. 
         FIG. 6  is a flowchart illustrating another embodiment of a method of the invention in which an appropriate anti-arrhythmia therapy according to a hemodynamic status of a patient is selected. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     The following detailed description of the invention refers to the accompanying drawings that illustrate exemplary embodiments consistent with this invention. Other embodiments are possible, and modifications may be made to the embodiments within the spirit and scope of the invention. Therefore, the following detailed description is not meant to limit the invention. Rather, the scope of the invention is defined by the appended claims. 
     It will be apparent to one of skill in the art that the invention, as described below, may be implemented in many different embodiments of hardware, software, firmware, and/or the entities illustrated in the figures. Any actual software and/or hardware described herein is not meant to limit the scope of the invention. Thus, the structure, operation and behavior of the invention will be described with the understanding that many modifications and variations of the embodiments are possible, given the level of detail presented herein. 
     Before describing the invention in detail, it is helpful to describe an example environment in which the invention may be implemented. The invention is particularly useful in the environment of an implantable cardiac device. Implantable cardiac devices include, for example, pacemakers, cardioverters and defibrillators. The term “implantable cardioverter defibrillator” or simply “ICD” is used herein to refer to any implantable cardioverter defibrillator (“ICD”) or implantable cardiac device capable of delivering therapy.  FIGS. 1A and 1B  illustrate such an environment. 
     As shown in  FIG. 1A , there is an exemplary ICD  10  in electrical communication with a patient&#39;s heart  12  by way of three leads,  20 ,  24  and  30 , suitable for delivering multi-chamber stimulation and pacing therapy. To sense atrial cardiac signals and to provide right atrial chamber stimulation therapy, ICD  10  is coupled to implantable right atrial lead  20  having at least an atrial tip electrode  22 , which typically is implanted in the patient&#39;s right atrial appendage. 
     To sense left atrial and ventricular cardiac signals and to provide left-chamber pacing therapy, ICD  10  is coupled to “coronary sinus” lead  24  designed for placement in the “coronary sinus region” via the coronary sinus for positioning a distal electrode adjacent to the left ventricle and/or additional electrode(s) adjacent to the left atrium. As used herein, the phrase “coronary sinus region” refers to the vasculature of the left ventricle, including any portion of the coronary sinus, great cardiac vein, left marginal vein, left posterior ventricular vein, middle cardiac vein, and/or small cardiac vein or any other cardiac vein accessible by the coronary sinus. 
     Accordingly, exemplary coronary sinus lead  24  is designed to receive atrial and ventricular cardiac signals and to deliver left ventricular pacing therapy using at least a left ventricular tip electrode  26 , left atrial pacing therapy using at least a left atrial ring electrode  27 , and shocking therapy using at least a left atrial coil electrode  28 . 
     ICD  10  is also shown in electrical communication with the patient&#39;s heart  12  by way of an implantable right ventricular lead  30  having, in this embodiment, a right ventricular tip electrode  32 , a right ventricular ring electrode  34 , a right ventricular (RV) coil electrode  36 , and an SVC coil electrode  38 . Typically, right ventricular lead  30  is transvenously inserted into heart  12  so as to place the right ventricular tip electrode  32  in the right ventricular apex so that RV coil electrode  36  will be positioned in the right ventricle and SVC coil electrode  38  will be positioned in the superior vena cava. Accordingly, right ventricular lead  30  is capable of receiving cardiac signals and delivering stimulation in the form of pacing and shock therapy to the right ventricle. 
       FIG. 1B  shows a simplified block diagram of ICD  10 , which is capable of treating both fast and slow arrhythmias with stimulation therapy, including cardioversion, defibrillation, and pacing stimulation. While a particular multi-chamber device is shown, it is shown for illustration purposes only, and one of skill in the art could readily duplicate, eliminate or disable the appropriate circuitry in any desired combination to provide a device capable of treating the appropriate chamber(s) with the desired cardioversion, defibrillation and pacing stimulation. 
     A housing  40  of ICD  10 , shown schematically in  FIG. 1B , is often referred to as the “can,” “case” or “case electrode” and may be programmably selected to act as the return electrode for all “unipolar” modes. Housing  40  may further be used as a return electrode alone or in combination with one or more of coil electrodes,  28 ,  36 , and  38  for shocking purposes. Housing  40  further includes a connector (not shown) having a plurality of terminals,  42 ,  44 ,  46 ,  48 ,  52 ,  54 ,  56 , and  58  (shown schematically and, for convenience, the names of the electrodes to which they are connected are shown next to the terminals). As such, to achieve right atrial sensing and pacing, the connector includes at least a right atrial tip terminal (AR TIP)  42  adapted for connection to atrial tip electrode  22 . 
     To achieve left chamber sensing, pacing and shocking, the connector includes at least a left ventricular tip terminal (VL TIP)  44 , a left atrial ring terminal (AL RING)  46 , and a left atrial shocking terminal (AL COIL)  48 , which are adapted for connection to left ventricular ring electrode  26 , left atrial tip electrode  27 , and left atrial coil electrode  28 , respectively. 
     To support right chamber sensing, pacing, and shocking the connector also includes a right ventricular tip terminal (VR TIP)  52 , a right ventricular ring terminal (VR RING)  54 , a right ventricular shocking terminal (RV COIL)  56 , and an SVC shocking terminal (SVC COIL)  58 , which are configured for connection to right ventricular tip electrode  32 , right ventricular ring electrode  34 , RV coil electrode  36 , and SVC coil electrode  38 , respectively. 
     At the core of ICD  10  is a programmable microcontroller  60  which controls the various modes of stimulation therapy. As is well known in the art, microcontroller  60  typically includes a microprocessor, or equivalent control circuitry, designed specifically for controlling the delivery of stimulation therapy and can further include RAM or ROM memory, logic and timing circuitry, state machine circuitry, and I/O circuitry. Typically, microcontroller  60  includes the ability to process or monitor input signals (data) as controlled by a program code stored in a designated block of memory. The details of the design of microcontroller  60  are not critical to the invention. Rather, any suitable microcontroller  60  can be used to carry out the functions described herein. The use of microprocessor-based control circuits for performing timing and data analysis functions are well known in the art. In specific embodiments of the invention, microcontroller  60  performs some or all of the steps associated with the sensing and prevention therapy in accordance with the invention. 
     Representative types of control circuitry that may be used with the invention include the microprocessor-based control system of U.S. Pat. No. 4,940,052 (Mann et al.) and the state-machines of U.S. Pat. Nos. 4,712,555 (Thornander et al.) and 4,944,298 (Sholder). For a more detailed description of the various timing intervals used within the ICDs and their inter-relationship, see U.S. Pat. No. 4,788,980 (Mann et al.). The &#39;052, &#39;555, &#39;298 and &#39;980 patents are incorporated herein by reference. 
     As shown in  FIG. 1B , an atrial pulse generator  70  and a ventricular pulse generator  72  generate pacing stimulation pulses for delivery by right atrial lead  20 , right ventricular lead  30 , and/or coronary sinus lead  24  via an electrode configuration switch  74 . It is understood that in order to provide stimulation therapy in each of the four chambers of the heart, atrial and ventricular pulse generators  70  and  72  may include dedicated, independent pulse generators, multiplexed pulse generators, or shared pulse generators. Pulse generators  70  and  72  are controlled by microcontroller  60  via appropriate control signals  76  and  78 , respectively, to trigger or inhibit the stimulation pulses. 
     Microcontroller  60  further includes timing control circuitry  79  which is used to control pacing parameters (e.g., the timing of stimulation pulses) as well as to keep track of the timing of refractory periods, PVARP intervals, noise detection windows, evoked response windows, alert intervals, marker channel timing, etc., which are well known in the art. Examples of pacing parameters include, but are not limited to, atrio-ventricular (AV) delay, interventricular (RV-LV) delay, atrial interconduction (A-A) delay, ventricular interconduction (V-V) delay, and pacing rate. 
     Switch  74  includes a plurality of switches for connecting the desired electrodes to the appropriate I/O circuits, thereby providing complete electrode programmability. Accordingly, switch  74 , in response to a control signal  80  from microcontroller  60 , determines the polarity of the stimulation pulses (e.g., unipolar, bipolar, combipolar, etc.) by selectively closing the appropriate combination of switches (not shown) as is known in the art. 
     Atrial sensing circuits  82  and ventricular sensing circuits  84  may also be selectively coupled to right atrial lead  20 , coronary sinus lead  24 , and right ventricular lead  30 , through switch  74  for detecting the presence of cardiac activity in each of the four chambers of the heart. Accordingly, the atrial (ATR. SENSE) and ventricular (VTR. SENSE) sensing circuits  82  and  84  may include dedicated sense amplifiers, multiplexed amplifiers, or shared amplifiers. Switch  74  determines the “sensing polarity” of the cardiac signal by selectively closing the appropriate switches, as is also known in the art. In this way, the clinician may program the sensing polarity independent of the stimulation polarity. 
     Each sensing circuit,  82  and  84 , preferably employs one or more low power, precision amplifiers with programmable gain and/or automatic sensitivity control, bandpass filtering, and a threshold detection circuit, as known in the art, to selectively sense the cardiac signal of interest. The automatic sensitivity control (ASC) enables ICD  10  to deal effectively with the difficult problem of sensing the low amplitude signal characteristics of atrial or ventricular fibrillation. Such sensing circuits,  82  and  84 , can be used to determine cardiac performance values used in the invention. 
     The outputs of atrial and ventricular sensing circuits  82  and  84  are connected to microcontroller  60  which, in turn, are able to trigger or inhibit atrial and ventricular pulse generators,  70  and  72 , respectively, in a demand fashion in response to the absence or presence of cardiac activity, in the appropriate chambers of the heart. Sensing circuits  82  and  84 , in turn, receive control signals over signal lines  86  and  88  from microcontroller  60  for purposes of measuring cardiac performance at appropriate times, and for controlling the gain, threshold, polarization charge removal circuitry (not shown), and timing of any blocking circuitry (not shown) coupled to the inputs of sensing circuits  82  and  84 . 
     For arrhythmia detection, ICD  10  utilizes the atrial and ventricular sensing circuits  82  and  84  to sense cardiac signals to determine whether a rhythm is physiologic or pathologic. The timing intervals between sensed events (e.g., P-waves, R-waves, and depolarization signals associated with fibrillation which are sometimes referred to as “F-waves” or “Fib-waves”) are then classified by microcontroller  60  by comparing them to a predefined rate zone limit (i.e., bradycardia, normal, low rate VT, high rate VT, and fibrillation rate zones) and various other characteristics (e.g., sudden onset, stability, physiologic sensors, and morphology, etc.) in order to determine the type of remedial therapy that is needed (e.g., bradycardia pacing, anti-tachycardia pacing, cardioversion shocks or defibrillation shocks, collectively referred to as “tiered therapy”). 
     Microcontroller  60  utilizes arrhythmia detection circuitry  75  and morphology detection circuitry  76  to recognize and classify arrhythmia so that appropriate therapy can be delivered. 
     Cardiac signals are also applied to the inputs of an analog-to-digital (A/D) data acquisition system  90 . Data acquisition system  90  is configured to acquire intracardiac electrogram signals, convert the raw analog data into a digital signal, and store the digital signals for later processing and/or telemetric transmission to an external device  102 . Data acquisition system  90  is coupled to right atrial lead  20 , coronary sinus lead  24 , and right ventricular lead  30  through switch  74  to sample cardiac signals across any pair of desired electrodes. 
     Advantageously, data acquisition system  90  can be coupled to microcontroller  60 , or other detection circuitry, for detecting an evoked response from heart  12  in response to an applied stimulus, thereby aiding in the detection of “capture.” Capture occurs when an electrical stimulus applied to the heart is of sufficient energy to depolarize the cardiac tissue, thereby causing the heart muscle to contract. Microcontroller  60  detects a depolarization signal during a window following a stimulation pulse, the presence of which indicates that capture has occurred. Microcontroller  60  enables capture detection by triggering ventricular pulse generator  72  to generate a stimulation pulse, starting a capture detection window using timing control circuitry  79  within microcontroller  60 , and enabling data acquisition system  90  via control signal  92  to sample the cardiac signal that falls in the capture detection window and, based on the amplitude, determines if capture has occurred. 
     The implementation of capture detection circuitry and algorithms are well known. See for example, U.S. Pat. No. 4,729,376 (DeCote, Jr.); U.S. Pat. No. 4,708,142 (DeCote, Jr.); U.S. Pat. No. 4,686,988 (Sholder); U.S. Pat. No. 4,969,467 (Callaghan et al.); and U.S. Pat. No. 5,350,410 (Kleks et al.), which patents are hereby incorporated herein by reference. The type of capture detection system used is not critical to the invention. 
     Microcontroller  60  is further coupled to a memory  94  by a suitable data/address bus  96 , wherein the programmable operating parameters used by microcontroller  60  are stored and modified, as required, in order to customize the operation of ICD  10  to suit the needs of a particular patient. Such operating parameters define, for example, pacing pulse amplitude, pulse duration, electrode polarity, rate, sensitivity, automatic features, arrhythmia detection criteria, and the amplitude, waveshape and vector of each shocking pulse to be delivered to the patient&#39;s heart  12  within each respective tier of therapy. 
     Advantageously, the operating parameters of ICD  10  may be non-invasively programmed into memory  94  through a telemetry circuit  100  in telemetric communication with external device  102 , such as a programmer, transtelephonic transceiver, or a diagnostic system analyzer. Telemetry circuit  100  is activated by microcontroller  60  by a control signal  106 . Telemetry circuit  100  advantageously allows intracardiac electrograms and status information relating to the operation of ICD  10  (as contained in microcontroller  60  or memory  94 ) to be sent to external device  102  through an established communication link  104 . 
     For examples of such devices, see U.S. Pat. No. 4,809,697, entitled “Interactive Programming and Diagnostic System for use with Implantable Pacemaker” (Causey, III et al.); U.S. Pat. No. 4,944,299, entitled “High Speed Digital Telemetry System for Implantable Device” (Silvian); and U.S. Pat. No. 6,275,734, entitled “Efficient Generation of Sensing Signals in an Implantable Medical Device such as a Pacemaker or ICD” (McClure et al.), which patents are hereby incorporated herein by reference. 
     In an embodiment, ICD  10  further includes a physiologic sensor  108  that can be used to detect changes in cardiac performance or changes in the physiological condition of the heart. Accordingly, microcontroller  60  can respond by adjusting the various pacing parameters (such as rate, AV Delay, RV-LV Delay, V-V Delay, etc.) in accordance with the embodiments of the invention. Microcontroller  60  controls adjustments of pacing parameters by, for example, controlling the stimulation pulses generated by the atrial and ventricular pulse generators  70  and  72 . While shown as being included within ICD  10 , it is to be understood that physiologic sensor  108  may also be external to ICD  10 , yet still be implanted within or carried by the patient. More specifically, sensor  108  can be located inside ICD  10 , on the surface of ICD  10 , in a header of ICD  10 , or on a lead (which can be placed inside or outside the bloodstream). 
     ICD  10  additionally includes a battery  110 , which provides operating power to all of the circuits shown in  FIG. 1B . For ICD  10 , which employs shocking therapy, battery  110  must be capable of operating at low current drains for long periods of time, and then be capable of providing high-current pulses (for capacitor charging) when the patient requires a shock pulse. Battery  110  must also have a predictable discharge characteristic so that elective replacement time can be detected. Accordingly, ICD  10  preferably employs lithium/silver vanadium oxide batteries, as is true for most (if not all) current devices. 
     ICD  10  further includes magnet detection circuitry (not shown), coupled to microcontroller  60 . It is the purpose of the magnet detection circuitry to detect when a magnet is placed over ICD  10 , which magnet may be used by a clinician to perform various test functions of ICD  10  and/or to signal microcontroller  60  that the external programmer  102  is in place to receive or transmit data to microcontroller  60  through telemetry circuit  100 . 
     As further shown in  FIG. 1B , ICD  10  is shown as having an impedance measuring circuit  112  which is enabled by microcontroller  60  via a control signal  114 . The known uses for an impedance measuring circuit  112  include, but are not limited to, lead impedance surveillance during the acute and chronic phases for proper lead positioning or dislodgement; detecting operable electrodes and automatically switching to an operable pair if dislodgement occurs; measuring respiration or minute ventilation; measuring thoracic impedance for determining shock thresholds; detecting when the device has been implanted; measuring stroke volume; and detecting the opening of heart valves, etc. The impedance measuring circuit  112  is advantageously coupled to switch  74  so that any desired electrode may be used. The impedance measuring circuit  112  is not critical to the invention and is shown only for completeness. 
     In the case where ICD  10  is intended to operate as a cardioverter, pacer or defibrillator, it must detect the occurrence of an arrhythmia and automatically apply an appropriate electrical therapy to the heart aimed at terminating the detected arrhythmia. To this end, microcontroller  60  further controls a shocking circuit  116  by way of a control signal  118 . The shocking circuit  116  generates shocking pulses of low (up to about 0.5 Joules), moderate (about 0.5-10 Joules), or high energy (about 11 to 40 Joules), as controlled by microcontroller  60 . Such shocking pulses are applied to the patient&#39;s heart  12  through at least two shocking electrodes (e.g., selected from left atrial coil electrode  28 , RV coil electrode  36 , and SVC coil electrode  38 ). As noted above, housing  40  may act as an active electrode in combination with RV electrode  36 , or as part of a split electrical vector using SVC coil electrode  38  or left atrial coil electrode  28  (i.e., using the RV electrode as a common electrode). 
     Cardioversion shocks are generally considered to be of low to moderate energy level (so as to minimize pain felt by the patient), and/or synchronized with an R-wave and/or pertaining to the treatment of tachycardia. Defibrillation shocks are generally of moderate to high energy level (i.e., corresponding to thresholds in the range of about 5-40 Joules), delivered asynchronously (since R-waves may be too disorganized to be recognized), and pertaining exclusively to the treatment of fibrillation. Accordingly, microcontroller  60  is capable of controlling the synchronous or asynchronous delivery of the shocking pulses. 
     With the description of an example environment, such as an ICD, in mind, features of the invention are described in more detail below. 
     As stated in the Background section, hemodynamic status describes whether the heart is pumping blood sufficiently to ensure adequate perfusion of vital organs. Hemodynamic status can be measured, for example, by one or more physiologic sensors located within an ICD, or on a lead that is placed in the bloodstream or at a location remote from the ICD. One example of a physiologic sensor used for hemodynamic measurement is a hemodynamic acoustic sensor. An acoustic sensor uses an acoustic transducer responsive to heart sounds to detect the hemodynamic status of a patient. For a more detailed description of hemodynamic measurement, including the use of acoustic sensors, see U.S. Pat. No. 6,477,406 B1 (Turcott), which is incorporated herein by reference. Another example of a hemodynamic sensor is a photoplethysmography sensor, such as that described in U.S. Pat. No. 6,409,675 (Turcott), which is incorporated herein by reference. Yet another example of a hemodynamic sensor is a pressure transducer placed in the right ventricle, as described in U.S. Pat. Nos. 3,942,536 (Mirowski et al.) and 6,221,024 (Miesel), which are incorporated herein by reference. 
     Conventional approaches to hemodynamic sensing face the common problem that it is difficult to provide accurate and reliable data in the face of mechanical artifact. For example, hemodynamic status is particularly difficult to measure due to motion-induced artifact associated with a change of posture and chest compressions that are likely to accompany a significant arrhythmia. To counter this problem, a device is needed, such as an ICD, that is immune from motion and electrical noise during hemodynamic measurement and can reliably use such hemodynamic measurement to deliver an appropriate electrical therapy. To that end, a device and method for hemodynamic measurement that is immune from motion and electrical noise, according to embodiments of the invention, will now be described. 
       FIG. 2  shows a graph  200  of an exemplary output from a hemodynamic sensor, such as an acoustic or photoplethysmography sensor. The signal of graph  200  is, for example, a template waveform  210  measured during a first hemodynamic state, plotted as signal amplitude versus time. Template waveform  210  should represent hemodynamic sensor data during a known physiologic state, such as during a benign state such as sinus rhythm. Therefore, the first hemodynamic state may be a normal sinus rhythm or pacing with a baseline AV delay, for example. 
     The template waveform  210  shown in  FIG. 2  is a model of an ideal sensor output unaffected by noise. However, most hemodynamic signals contain noise and artifact that can degrade the quality of a template. Examples of such noise include electronic noise and respiration. Electronic noise is recognizable as low amplitude, high frequency variability of the signal, which gives the trace a thick appearance in the plot. Respiration is recognizable as a low-frequency oscillation in the baseline of the hemodynamic signal. To minimize the effects of electronic, respiratory, and other noise components, the raw hemodynamic signal can be filtered using a band-pass filter, for example. Some intrinsic respiratory variability may remain, but it is greatly attenuated relative to the raw signal. 
     To acquire a template waveform that best represents a non-pathologic rhythm, the template waveform can be formed by superimposing multiple pulse traces in time and computing an ensemble average over one or more respiratory cycles. This can be done by synchronizing the traces relative to sensed cardiac events. For example, a threshold crossing of an ECG is used to identify a point of onset of ventricular contraction. The portions of the filtered hemodynamic signal that fall between successive threshold crossings are superimposed, and the average of the ensemble of traces is computed. The result serves as the template waveform. Other methods of obtaining a template exist and are known in the art. For example, rather than performing the alignment based on synchronization with an auxiliary signal, as discussed above in reference to the ECG signal, one could align the traces by performing a cross-correlation between a trace and the current template or a reference trace. 
     The quality of the template can be further improved by acquiring the template data during periods when noise is not present or is minimally present. For example, by monitoring an activity sensor, which is commonly included in contemporary ICDs, template data could be acquired when the patient is not moving. Alternatively, intrinsic analysis of the hemodynamic sensor signal could be performed to select periods when the signal fidelity is high, which implies that motion and other sources of noise are not significant. High-fidelity data segments could then be used to construct the template. 
       FIG. 3  illustrates an examplary series  300  of test waveforms  320 - 330  with varying levels of white Gaussian noise applied. In  FIG. 3 , the standard deviation of the additive noise is varied from 0.0 (as shown by test waveform  320 ) to 0.5 (as shown by test waveform  330 ) times the maximum of the full-amplitude noiseless test waveform  320 . As the noise amplitude is increased, note how quickly the waveform of interest becomes obscured. The invention allows the measuring of hemodynamic performance that is essentially unaffected by increases in noise amplitude.  FIG. 4  corresponds to the test waveforms  320 - 330  of  FIG. 3  and will be discussed after the embodiments of the invention are described. 
     In the description to follow, the terms ‘autocorrelation’ and ‘cross-correlation’ are used. These terms refer to well-known mathematical operations that are commonly used in engineering and data analysis. Their use in the following description is illustrative, and should not be taken in a limiting sense. The terms ‘autocorrelation’ and ‘cross-correlation’ represent specific techniques of a more general class of mathematical operations, which are referred to herein as ‘autocharacterization’ and ‘cross-characterization.’ Any technique that provides a quantitative comparison of two waveforms can serve in place of the autocorrelation and cross-correlation steps described below. 
     An example technique of quantitative comparison of two waveforms is as follows. Point-wise differences between two waveforms can be calculated, squared, and summed. One waveform is then translocated relative to the other, and the calculation repeated. This process is continued so that a function is obtained which expresses the dependence of the sum of squared differences between the two waveforms on the relative translocation of the two waveforms. This is similar to the correlation function, except that here it is the sum of squared differences, while the correlation function is based on average squared value. The minimum value achieved by this function occurs at the time lag or translocation that yields the best fit between the two waveforms, whereas the maximum value of a correlation function occurs at the time lag or translocation that yields the worst fit. 
     Alternatively, rather than obtaining a function whose independent variable is the time lag, or translocation, between the two waveforms, one could calculate a single measure of similarity at a single lag or translocation. For example, aligning two functions relative to ventricular depolarization (e.g., as measured by an intracardiac electrogram) and obtaining a measure that represents their degree of similarity would avoid the need for repetitive translocations and calculations described above and implicit in the computation of the correlation function. The degree of similarity could be quantified as the sum of squared differences, or, analogous to the correlation function, the sum of squared values. Thus, while the invention is described in terms of the autocorrelation and cross-correlation operations, these terms are intended to represent a broader class of operations, which are more appropriately termed ‘autocharacterization’ and ‘cross-characterization.’ 
     Embodiments of the invention will now be described. 
     A method  500  of measuring hemodynamic performance of a patient&#39;s heart in accordance with the invention is illustrated in the flowchart of  FIG. 5 . According to an embodiment of the invention, the method  500  begins at step  560 , and immediately continues at step  562 . In step  562 , a template waveform is obtained that represents hemodynamic performance of a heart during a first hemodynamic state. The template waveform is akin to template waveform  210  of  FIG. 2 , which represents output from a physiologic sensor such as an acoustic or photoplethysmography sensor. According to one embodiment of the invention, the first hemodynamic state is that of a normal sinus rhythm. According to another embodiment of the invention, the first hemodynamic state is heart pacing with a baseline atrioventricular (AV) delay. 
     In step  564 , an autocorrelation of the template waveform is obtained. The autocorrelation may be obtained in any way that is known by those skilled in the art of signal processing. One example of performing an autocorrelation of the template waveform is to transform the template waveform signal into the frequency domain from the time domain, multiply its spectrum with itself, and perform an inverse transformation back into the time domain. In step  566 , a maximum autocorrelation value is identified from the obtained autocorrelation. 
     In step  568 , a test waveform is obtained during a second hemodynamic state. The test waveform is akin to any of test waveforms  320 - 330  of  FIG. 3 . The test waveform represents current output from a physiologic sensor such as an acoustic or photoplethysmography sensor. According to one embodiment of the invention, the second hemodynamic state is that of a tachycardia rhythm. According to another embodiment of the invention, the second hemodynamic state includes a test atrioventricular (AV) delay. That is, the AV delay can be varied and the resultant test waveforms captured for the different AV delay values. 
     In step  570 , a cross-correlation of the template waveform and the test waveform is performed to obtain a cross-correlation function. The cross-correlation may be obtained in any way that is known by those skilled in the art of signal processing. One example of performing a cross-correlation of the template waveform with the test waveform is to transform both waveform signals into the frequency domain from the time domain, multiply the spectrum of the template waveform with the spectrum of the test waveform, and perform an inverse transformation back into the time domain. In step  572 , a maximum value of the cross-correlation function is obtained. 
     In step  574 , the maximum autocorrelation value is compared with the maximum cross-correlation function value. This comparison is a measurement of hemodynamic status of the second hemodynamic state with the template waveform being used as a baseline. In an embodiment of the invention, step  574  includes comparing a predetermined threshold against a difference between the maximum autocorrelation value and the maximum cross-correlation function value. Method  500  terminates at step  576 . 
     According to one embodiment of the invention, step  574  includes determining if the maximum cross-correlation function value is less than the maximum autocorrelation value by a predetermined status low threshold. If so, the hemodynamic status of the second hemodynamic state is determined as low. This means that the current hemodynamic status of the patient is deemed to be significantly less than during template waveform acquisition. This may mean, for example, that the detected tachycardia is hemodynamically unstable or that the current test AV delay is inferior to the baseline AV delay. The magnitude of the threshold can vary according to the application. For example, a different threshold may be used for arrhythmia analysis than would be used for AV/VV optimization. 
     According to another embodiment of the invention, step  574  includes determining if the maximum cross-correlation function value is greater than the maximum autocorrelation value by a predetermined status high threshold. If so, the hemodynamic status of the second hemodynamic state is determined as high. This means that the current hemodynamic status of the patient is deemed to be significantly greater than during template waveform acquisition. This may mean, for example, that the current test AV delay is superior to the baseline AV delay. The magnitude of the threshold can vary according to the application. 
     The maximum cross-correlation function value is reduced by a reduction in signal amplitude and also by a deviation of signal morphology away from that of the template. The reduction in signal amplitude and deviation of signal morphology are expected for some hemodynamic sensors during unstable arrhythmias. Both effects (amplitude and morphology) on the maximum values are in the same direction and improve performance during arrhythmia discrimination. 
     A method  600  of selecting an appropriate anti-arrhythmia therapy for a patient according to the patient&#39;s hemodynamic status, in accordance with the invention, is illustrated in the flowchart of  FIG. 6 . According to an embodiment of the invention, the method  600  begins at step  602 , and immediately continues at step  604 . In step  604 , electrical activity of a patient&#39;s heart is monitored to detect an arrhythmia. In step  606 , hemodynamic performance of the heart is monitored. In an embodiment, hemodynamic performance is monitored as in method  500 , previously described with reference to  FIG. 5 . In step  608 , an appropriate anti-arrhythmia therapy is selected to treat the arrhythmia. One factor involved with this selection is whether the patient is hemodynamically stable or unstable. For example, if hemodynamically stable, the patient is likely to be conscious, and therefore treated with lower voltage therapies. If hemodynamically unstable, the patient is treated more quickly and aggressively. In step  610 , the method terminates. 
     As stated earlier, it is important to note that applications of the invention are not limited to hemodynamic assessment, but may be applied to the assessment of any electrical signal. When used during hemodynamic assessment, however, applications of the technique are not limited to hemodynamic assessment during arrhythmia detection. Rather, the technique can be used in any context that requires hemodynamic measurement, such as atrio-ventricular/ventricular-ventricular (AV/VV) optimization, disease monitoring, orthostatic hypotension detection and therapy, for example. 
     It will be appreciated by those skilled in the art that the above-described method can be used within the hardware, software, and/or firmware of a pacing system, such as the ICD described earlier with reference to  FIGS. 1A and 1B , for example. 
     The technique of method  500  functions reliably in the face of electrical noise and motion artifact since the maximum cross-correlation function value is relatively unaffected by additive noise. This is demonstrated further with reference to  FIGS. 2 ,  3 , and  4 , which show a computer-simulated comparison between a conventional amplitude-based technique as compared to the cross-characterization technique of the invention. 
     As previously described, the waveform  210  of  FIG. 2  serves as a template waveform showing output from a physiologic sensor, such as an acoustic or photoplethysmography sensor. Template waveform  210  is cross-correlated with a test waveform, such as any of test waveforms  320 - 330  of  FIG. 3 . The test waveforms  320 - 330  represent current output of the physiologic sensor, each with varying levels of white Gaussian noise applied. Test waveform  320  has no noise applied, for example, and test waveform  324  has a standard deviation of additive noise of 0.2 times the maximum of the full-amplitude test waveform with no noise applied (i.e., test waveform  320 ). The template waveform  210  is cross-correlated with each of test waveforms  320 - 330 , and the maximum of each of the resulting functions is taken as a measure of hemodynamic status. 
     In the computer simulation of which this discussion describes a part, ten thousand test waveforms were analyzed at each of a range of noise levels. Half of the test waveforms had the same amplitude as the original template waveform, while the remainder had a 50% attenuation in amplitude. The sensitivity and specificity of the cross-correlation technique of the invention in detecting the reduced amplitude signal was determined. The sensitivity and specificity of the cross-correlation technique was then compared to the sensitivity and specificity of a conventional amplitude-based technique used to analyze the same set of test waveforms. The algorithm used for the computer simulation was tasked with detecting a 50% reduction in signal amplitude. The detection threshold for the cross-correlation technique was halfway between a maxima of the cross-correlation functions (i.e., template waveform crossed with a full-amplitude noiseless test waveform, and template waveform crossed with a half-amplitude noiseless test waveform). The detection threshold for the amplitude technique was halfway between a maxima of a full-amplitude noiseless test waveform and a half-amplitude noiseless test waveform. 
     In  FIG. 3 , the sensitivity and specificity for the conventional amplitude technique and the cross-correlation technique of the invention are shown for each test waveform  320 - 330 . It can be seen that for low noise levels, both techniques can reliably distinguish the full-amplitude from the half-amplitude test waveforms, since each technique shows a sensitivity and specificity of at or very near 100% (see the sensitivities and specificities of test waveforms  320  and  322 ). However, for higher noise levels, the amplitude technique fails. For example, the sensitivities of the amplitude technique for test waveforms  326 ,  328 , and  330  are at or very nearly zero, while the specificities are at or nearly one. This indicates that for test waveforms  326 ,  328 , and  330 , the amplitude technique diagnosed all test waveforms as being of full amplitude. It is unlikely that a threshold adjustment would show improvement. 
       FIG. 4  corresponds to the test waveforms  320 - 330  of  FIG. 3  and illustrates a comparison of the sensitivities and specificities of a conventional amplitude technique and the cross-correlation technique of the invention for detecting a 50% reduction in signal amplitude. The calculated sensitivities and specificities shown in  FIG. 3  are plotted as functions  400  of noise level. Solid lines  432  and  434  represent the data from using the cross-correlation technique of the invention. The dashed lines  436  and  438  represent the data from using the conventional amplitude-based technique. The sensitivity chart  440  clearly shows the difference in sensitivity between the two techniques at normalized noise levels greater than about 0.2. The results of the simulation show that even though the presence of the test waveforms becomes difficult to visually detect in the raw data for normalized noise levels greater than about 0.2 (see  FIG. 3 ), the sensitivity and specificity of the cross-correlation technique remains quite good for all noise levels tested (as shown in  FIG. 4 ). 
     The cross-characterization technique of the invention described herein significantly improves noise-immunity in hemodynamic sensing as compared to conventional techniques. Use of cross-characterization techniques, such as cross-correlation, allows for hemodynamic measurement that is immune from motion and noise and can reliably be used to deliver appropriate electrical therapies to a patient, possibly even enabling ambulatory hemodynamic assessment. 
     Example embodiments of the methods, systems, and components of the invention have been described herein. As noted elsewhere, these example embodiments have been described for illustrative purposes only, and are not limiting. Other embodiments are possible and are covered by the invention. Such embodiments will be apparent to persons skilled in the relevant art(s) based on the teachings contained herein. Thus, the breadth and scope of the invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.