Patent Publication Number: US-8116870-B2

Title: Capture detection for multi-chamber pacing

Description:
RELATED PATENT DOCUMENTS 
     This application is a continuation of U.S. patent application Ser. No. 11/116,563 filed on Apr. 28, 2005, which is incorporated herein by reference in its entirety. 
    
    
     FIELD OF THE INVENTION 
     The present invention relates generally to cardiac devices and methods, and, more particularly, to cardiac devices and methods used in detecting capture in multi-chamber pacing. 
     BACKGROUND OF THE INVENTION 
     When functioning normally, the heart produces rhythmic contractions and is capable of pumping blood throughout the body. The heart has specialized conduction pathways in both the atria and the ventricles that enable the rapid conduction of excitation impulses (i.e. depolarizations) from the SA node throughout the myocardium. These specialized conduction pathways conduct the depolarizations from the SA node to the atrial myocardium, to the atrioventricular node, and to the ventricular myocardium to produce a coordinated contraction of both atria and both ventricles. 
     The conduction pathways synchronize the contractions of the muscle fibers of each chamber as well as the contraction of each atrium or ventricle with the opposite atrium or ventricle. Without the synchronization afforded by the normally functioning specialized conduction pathways, the heart&#39;s pumping efficiency is greatly diminished. Patients who exhibit pathology of these conduction pathways can suffer compromised cardiac output. 
     Cardiac rhythm management devices have been developed that provide pacing stimulation to one or more heart chambers in an attempt to improve the rhythm and coordination of atrial and/or ventricular contractions. Cardiac rhythm management devices typically include circuitry to sense signals from the heart and a pulse generator for providing electrical stimulation to the heart. Leads extending into the patient&#39;s heart chamber and/or into veins of the heart are coupled to electrodes that sense the heart&#39;s electrical signals and for delivering stimulation to the heart in accordance with various therapies for treating cardiac arrhythmias. 
     Pacemakers are cardiac rhythm management devices that deliver a series of low energy pace pulses timed to assist the heart in producing a contractile rhythm that maintains cardiac pumping efficiency. Pace pulses may be intermittent or continuous, depending on the needs of the patient. There exist a number of categories of pacemaker devices, with various modes for sensing and pacing one or more heart chambers. 
     A pace pulse must exceed a minimum energy value, or capture threshold, to produce a contraction. It is desirable for a pace pulse to have sufficient energy to stimulate capture of the heart chamber without expending energy significantly in excess of the capture threshold. Thus, accurate determination of the capture threshold is required for efficient pace energy management. If the pace pulse energy is too low, the pace pulses may not reliably produce a contractile response in the heart chamber and may result in ineffective pacing. If the pace pulse energy is too high, the patient may experience discomfort and the battery life of the device will be shorter. 
     Detecting if a pacing pulse “captures” the heart and produces a contraction allows the pacemaker to adjust the energy level of pace pulses to correspond to the optimum energy expenditure that reliably produces capture. Further, capture detection allows the pacemaker to initiate a back-up pulse at a higher energy level whenever a pace pulse does not produce a contraction. 
     When a pace pulse produces a contraction in the heart chamber, the electrical cardiac signal preceding the contraction is denoted the captured response. The captured response typically includes an electrical signal, denoted the evoked response signal, associated with the heart contraction, along with a superimposed signal associated with residual post pace polarization at the electrode-tissue interface. The magnitude of the residual post pace polarization signal, or pacing artifact, may be affected by a variety of factors including lead polarization, after-potential from the pace pulse, lead impedance, patient impedance, pace pulse width, and pace pulse amplitude, for example. The evoked response may be affected by interaction with intrinsic heart activity and resulting in a fusion or pseudofusion response. 
     Multi-chamber pacemakers may include electrodes positioned to contact cardiac tissue within or adjacent to both the left and the right ventricles for pacing both the left and right ventricles. This type of device allows bi-ventricular pacing therapy to be applied, for example, to coordinate ventricular contractions when a patient suffers from congestive heart failure (CHF). Furthermore, multi-chamber pacemakers may include electrodes positioned to contact tissue within or adjacent to both the left and the right atria to enable bi-atrial pacing. 
     It is desirable to determine if pacing pulses delivered to multiple heart chambers produce a captured response in one, both, or none of the paced chambers. The present invention provides methods and systems used for enhancing the discrimination of the cardiac response to multi-chamber pacing and provides various advantages over the prior art. 
     SUMMARY OF THE INVENTION 
     The present invention involves approaches for detecting various capture conditions during multi-chamber pacing. One embodiment of the invention involves a method for detection various capture conditions. Pacing pulses are delivered to left and right heart chambers during a cardiac cycle. A cardiac electrogram signal is sensed following the delivery of the pacing pulses. The method includes distinguishing between left chamber capture only, right chamber capture only, and bi-chamber capture based on characteristics of the cardiac electrogram signal. 
     According to one aspect, the pacing pulses are delivered to left and right ventricles. The method includes distinguishing between left ventricular capture only, right ventricular capture only, and bi-ventricular capture. 
     The cardiac electrogram signal may be sensed, for example, using an electrode positioned in, on or within a vein of the right heart chamber, using an electrode positioned in, on, or within a vein of the left heart chamber or using both left heart chamber and right heart chamber electrodes. 
     In one implementation, each of the templates, comprising detection windows having dimensions of time and amplitude, are associated with left chamber capture, right chamber capture, or bi-chamber capture. The cardiac electrogram signal is compared to one or more of the templates to determine the type of capture condition. The detection windows are associated with an expected feature, e.g., peaks, of the cardiac electrogram under a particular capture condition. 
     Another embodiment of the invention involves a cardiac device. The cardiac device includes a sensing channel configured to sense a cardiac electrogram signal following delivery of pacing pulses delivered to left and right heart chambers, respectively, during a cardiac cycle. A processor coupled to the sensing circuitry, the processor configured to distinguish between left chamber capture only, right chamber capture only, and bi-chamber capture based on characteristics of the cardiac signal. 
     The above summary of the present invention is not intended to describe each embodiment or every implementation of the present invention. Advantages and attainments, together with a more complete understanding of the invention, will become apparent and appreciated by referring to the following detailed description and claims taken in conjunction with the accompanying drawings. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a flowchart illustrating a method of capture detection in accordance with embodiments of the invention; 
         FIG. 2  is a partial view of one embodiment of an implantable medical device suitable for implementing multi-chamber capture detection in accordance with embodiments of the invention; 
         FIG. 3  is a block diagram of an implantable medical device suitable for implementing multi-chamber capture detection in accordance with embodiments of the invention. 
         FIGS. 4A and 4B  provide a flowchart illustrating a method of bi-ventricular capture detection in accordance with embodiments of the invention; 
         FIG. 5  is a graph illustrating detection windows used for detecting bi-ventricular capture and right ventricle only capture in accordance with embodiments of the invention; 
         FIG. 6  is a graph illustrating detection windows used for detecting bi-ventricular capture and left ventricle only capture in accordance with embodiments of the invention; 
         FIG. 7  is a flowchart illustrating a method of performing a multi-chamber capture threshold test in accordance with embodiments of the invention; 
         FIG. 8  is a flowchart illustrating a method of confirming the capture condition in accordance with embodiments of the invention; and 
         FIGS. 9A and 9B  are flowcharts illustrating methods of selecting an electrode for capture sensing in accordance with embodiments of the invention. 
     
    
    
     While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail below. It is to be understood, however, that the intention is not to limit the invention to the particular embodiments described. On the contrary, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims. 
     DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS 
     In the following description of the illustrated embodiments, references are made to the accompanying drawings forming a part hereof, and in which are shown by way of illustration, various embodiments by which the invention may be practiced. It is to be understood that other embodiments may be utilized, and structural and functional changes may be made without departing from the scope of the present invention. 
     A pacemaker or other cardiac rhythm management device may determine whether an applied electrical pacing stimulus captures a heart chamber. The systems and methods described herein involve the use of features of a cardiac electrogram to discriminate between various types of cardiac responses to multi-chamber pacing. The approaches of the present invention provide for enhanced capture threshold testing and/or beat to beat automatic capture verification for multi-chamber pacing, for example. 
     Several functions of cardiac devices rely on the heart response consistency. For example, automatic capture threshold testing and/or automatic capture verification algorithms may rely on templates of the heart&#39;s response as the basis for determining whether a future pacing stimulus produces a particular type of response. Templates representative of various types of cardiac responses may comprise one or more detection windows. The detection windows are compared to a cardiac signal following delivery of multi-chamber pacing. In multi-chamber pacing, pacing pulses delivered to two opposite, i.e., left and right, heart chambers during a cardiac cycle. In accordance with embodiments of the invention, the cardiac signal following pacing is analyzed to discriminate, for example between left heart chamber capture, right heart chamber capture, multi-chamber capture, fusion and non-capture. 
       FIG. 1  is a flowchart illustrating a method of multi-chamber capture detection in accordance with embodiments of the invention. Pacing pulses are delivered  110  to left and right heart chambers during a cardiac cycle. For example, a pacing pulse may be delivered to the left ventricle (LV) and to the right ventricle (RV). The pacing pulses may be delivered over separate pacing channels and may be delivered substantially simultaneously or may be separated in time by an interventricular delay (IVD). The cardiac signal following delivery of the pacing pulses is sensed  120 . The cardiac signal may be sensed, for example, using an evoked response sensing channel that is configured for detection of the cardiac response to the multi-chamber pacing. The cardiac response to the multi-chamber pacing is determined based on characteristics of the sensed cardiac signal. Capture of the left chamber only, right chamber only, multi-chamber capture, fusion or non-capture may be discriminated  130 . 
     The embodiments of the present system illustrated herein are generally described as being implemented in a patient implantable medical device (PIMD) such as a pacemaker/defibrillator (PD) that may operate in numerous pacing modes known in the art. Various types of multiple chamber implantable cardiac pacemaker/defibrillators are known in the art and may be used in connection with cardiac devices and methods that provide multi-chamber capture detection in accordance with the approaches of the present invention. The methods of the present invention may be implemented in a variety of implantable or patient-external cardiac rhythm management devices, including multi-chamber pacemakers, defibrillators, cardioverters, bi-ventricular pacemakers, cardiac resynchronizers, and cardiac monitoring systems, for example. 
     A device suitable for implementing the capture detection methods of the present invention may include stimulation circuitry from delivering stimulation pulses to the heart and includes sensing circuitry comprising electrodes electrically coupled to the heart. Leads from the sensing and/or stimulation circuitry are coupled to electrodes positioned within heart chambers, positioned within veins of the heart, and/or positioned on the heart. The electrodes sense the heart&#39;s electrical signals, which are denoted cardiac electrogram signals. Each lead may include multiple electrodes, and each electrode may be used to sense a separate electrogram signal for capture detection. 
     Although the present system is described in conjunction with an implantable cardiac pacemaker/defibrillator having a microprocessor-based architecture, it will be understood that the implantable pacemaker/defibrillator (or other device) may be implemented using any logic-based circuit architecture, if desired. 
     Referring now to  FIG. 2  of the drawings, there is shown a partial view of a cardiac rhythm management device that may be used to implement multi-chamber capture detection in accordance with the present invention. The cardiac rhythm management device in  FIG. 2  includes a pacemaker/defibrillator  800  electrically and physically coupled to a lead system  802 . The housing and/or header of the pacemaker/defibrillator  800  may incorporate one or more electrodes  908 ,  909  used to provide electrical stimulation energy to the heart and to sense cardiac electrical activity. The pacemaker/defibrillator  800  may utilize all or a portion of the pacemaker/defibrillator housing as a can electrode  909 . The pacemaker/defibrillator  800  may include an indifferent electrode  908  positioned, for example, on the header or the housing of the pacemaker/defibrillator  800 . If the pacemaker/defibrillator  800  includes both a can electrode  909  and an indifferent electrode  908 , the electrodes  908 ,  909  typically are electrically isolated from each other. 
     The lead system  802  is used to detect electric cardiac signals produced by the heart  801  and to provide electrical energy to the heart  801  under certain predetermined conditions to treat cardiac arrhythmias. The lead system  802  may include one or more electrodes used for pacing, sensing, and/or defibrillation. In the embodiment shown in  FIG. 2 , the lead system  802  includes an intracardiac right ventricular (RV) lead system  804 , an intracardiac right atrial (RA) lead system  805 , an intracardiac left ventricular (LV) lead system  806 , and an extracardiac left atrial (LA) lead system  808 . The lead system  802  of  FIG. 2  illustrates one embodiment that may be used in connection with the multi-chamber capture detection methodologies described herein. Other leads and/or electrodes may additionally or alternatively be used. 
     The lead system  802  may include intracardiac leads  804 ,  805 ,  806  implanted in a human body with portions of the intracardiac leads  804 ,  805 ,  806  inserted into a heart  801 . The intracardiac leads  804 ,  805 ,  806  include various electrodes positionable within the heart for sensing electrical activity of the heart and for delivering electrical stimulation energy to the heart, for example, pacing pulses and/or defibrillation shocks to treat various arrhythmias of the heart. 
     As illustrated in  FIG. 2 , the lead system  802  may include one or more extracardiac leads  808  having electrodes, e.g., epicardial electrodes, positioned at locations outside the heart for sensing and pacing one or more heart chambers. 
     The right ventricular lead system  804  illustrated in  FIG. 2  includes an SVC-coil  816 , an RV-coil  814 , an RV-ring electrode  811 , and an RV-tip electrode  812 . The right ventricular lead system  804  extends through the right atrium  820  and into the right ventricle  819 . In particular, the RV-tip electrode  812 , RV-ring electrode  811 , and RV-coil electrode  814  are positioned at appropriate locations within the right ventricle  819  for sensing and delivering electrical stimulation pulses to the heart  801 . The SVC-coil  816  is positioned at an appropriate location within the right atrium chamber  820  of the heart  801  or a major vein leading to the right atrial chamber  820  of the heart  801 . 
     In one configuration, the RV-tip electrode  812  referenced to the can electrode  909  may be used to implement unipolar pacing and/or sensing in the right ventricle  819 . Bipolar pacing and/or sensing in the right ventricle may be implemented using the RV-tip  812  and RV-ring  811  electrodes. In yet another configuration, the RV-ring  811  electrode may optionally be omitted, and bipolar pacing and/or sensing may be accomplished using the RV-tip electrode  812  and the RV-coil  814 , for example. The RV-coil  814  and the SVC-coil  816  are defibrillation electrodes. 
     The left ventricular lead  806  includes an LV distal electrode  813  and an LV proximal electrode  817  located at appropriate locations in or about the left ventricle  824  for pacing and/or sensing the left ventricle  824 . The left ventricular lead  806  may be guided into the right atrium  820  of the heart via the superior vena cava. From the right atrium  820 , the left ventricular lead  806  may be deployed into the coronary sinus ostium, the opening of the coronary sinus  850 . The lead  806  may be guided through the coronary sinus  850  to a coronary vein of the left ventricle  824 . This vein is used as an access pathway for leads to reach the surfaces of the left ventricle  824  which are not directly accessible from the right side of the heart. Lead placement for the left ventricular lead  806  may be achieved via subclavian vein access and a preformed guiding catheter for insertion of the LV electrodes  813 ,  817  adjacent to the left ventricle. 
     Unipolar pacing and/or sensing in the left ventricle may be implemented, for example, using the LV distal electrode referenced to the can electrode  909 . The LV distal electrode  813  and the LV proximal electrode  817  may be used together as bipolar sense and/or pace electrodes for the left ventricle. The left ventricular lead  806  and the right ventricular lead  804 , in conjunction with the pacemaker/defibrillator  800 , may be used to provide cardiac resynchronization therapy such that the ventricles of the heart are paced substantially simultaneously, or in phased sequence, to provide enhanced cardiac pumping efficiency for patients suffering from chronic heart failure. 
     The right atrial lead  805  includes a RA-tip electrode  856  and an RA-ring electrode  854  positioned at appropriate locations in the right atrium  820  for sensing and pacing the right atrium  820 . In one configuration, the RA-tip  856  referenced to the can electrode  909 , for example, may be used to provide unipolar pacing and/or sensing in the right atrium  820 . In another configuration, the RA-tip electrode  856  and the RA-ring electrode  854  may be used to provide bipolar pacing and/or sensing. 
       FIG. 2  illustrates one embodiment of a left atrial lead system  808 . In this example, the left atrial lead  808  is implemented as an extracardiac lead with LA distal  818  and LA proximal  815  electrodes positioned at appropriate locations outside the heart  801  for sensing and pacing the left atrium  822 . Unipolar pacing and/or sensing of the left atrium may be accomplished, for example, using the LA distal electrode  818  to the can  909  pacing vector. The LA proximal  815  and LA distal  818  electrodes may be used together to implement bipolar pacing and/or sensing of the left atrium  822 . The right atrial lead  805  and the left atrial lead  808  may be used in conjunction with the pacemaker/defibrillator  800  to provide bi-atrial pacing. 
     Referring now to  FIG. 3 , there is shown a block diagram of a cardiac pacemaker/defibrillator  900  suitable for implementing multi-chamber capture detection methods of the present invention.  FIG. 3  shows a cardiac pacemaker/defibrillator  900  divided into functional blocks. It is understood by those skilled in the art that there exist many possible configurations in which these functional blocks can be arranged. The example depicted in  FIG. 3  is one possible functional arrangement. Other arrangements are also possible. For example, more, fewer or different functional blocks may be used to describe a cardiac pacemaker/defibrillator suitable for implementing the methodologies for multi-chamber capture detection in accordance with the present invention. In addition, although the cardiac pacemaker/defibrillator  900  depicted in  FIG. 3  contemplates the use of a programmable microprocessor-based logic circuit, other circuit implementations may be utilized. 
     The cardiac pacemaker/defibrillator  900  depicted in  FIG. 3  includes circuitry for receiving cardiac signals from a heart and delivering electrical stimulation energy to the heart in the form of pacing pulses or defibrillation shocks. In one embodiment, the circuitry of the cardiac pacemaker/defibrillator  900  is encased and hermetically sealed in a housing  901  suitable for implanting in a human body. Power to the cardiac pacemaker/defibrillator  900  is supplied by an electrochemical battery  980 . A connector block (not shown) is attached to the housing  901  of the cardiac pacemaker/defibrillator  900  to allow for the physical and electrical attachment of the lead system conductors to the circuitry of the cardiac pacemaker/defibrillator  900 . 
     The cardiac pacemaker/defibrillator  900  may be a programmable microprocessor-based system, including a control system  920  and a memory  970 . The memory  970  may store parameters for various pacing, defibrillation, and sensing modes, along with other parameters. Further, the memory  970  may store data indicative of cardiac signals received by other components of the cardiac pacemaker/defibrillator  900 . The memory  970  may be used, for example, for storing historical cardiac electrogram and therapy data. The historical data storage may include, for example, data obtained from long-term patient monitoring used for trending and/or other diagnostic purposes. Historical data, as well as other information, may be transmitted to an external programmer unit  990  as needed or desired. 
     The control system  920  and memory  970  may cooperate with other components of the cardiac pacemaker/defibrillator  900  to control the operations of the cardiac pacemaker/defibrillator  900 . The control system  920  depicted in  FIG. 3  incorporates detection window circuitry  926  configured to provide multi-chamber capture detection as described herein. 
     The control system  920  further includes a cardiac response classification processor  925  that works in conjunction with the detection window circuitry  926 . The cardiac response classification processor  925  performs the function of analyzing the location of cardiac signal features with respect to one or more detection windows to determine the cardiac response to pacing. 
     The control system  920  may include additional functional components including a pacemaker control circuit  922 , an arrhythmia detector  921 , along with other components for controlling the operations of the cardiac pacemaker/defibrillator  900 . 
     Telemetry circuitry  960  may be implemented to provide communications between the cardiac pacemaker/defibrillator  900  and an external programmer unit  990 . In one embodiment, the telemetry circuitry  960  and the programmer unit  990  communicate using a wire loop antenna and a radio frequency telemetric link, as is known in the art, to receive and transmit signals and data between the programmer unit  990  and the telemetry circuitry  960 . In this manner, programming commands and other information may be transferred to the control system  920  of the cardiac pacemaker/defibrillator  900  from the programmer unit  990  during and after implant. In addition, stored cardiac data pertaining to capture threshold, capture detection and/or cardiac response classification, for example, along with other data, may be transferred to the programmer unit  990  from the cardiac pacemaker/defibrillator  900 . 
     The telemetry circuitry  960  may provide for communication between the cardiac pacemaker/defibrillator  900  and an advanced patient management (APM) system. The advanced patient management system allows physicians or other personnel to remotely and automatically monitor cardiac and/or other patient conditions. In one example, a cardiac pacemaker/defibrillator, or other device, may be equipped with various telecommunications and information technologies that enable real-time data collection, diagnosis, and treatment of the patient. Various embodiments described herein may be used in connection with advanced patient management. 
     Methods, structures, and/or techniques described herein, which may be adapted to provide for remote patient/device monitoring, diagnosis, therapy, or other APM related methodologies, may incorporate features of one or more of the following references: U.S. Pat. Nos. 6,221,011; 6,270,457; 6,277,072; 6,280,380; 6,312,378; 6,336,903; 6,358,203; 6,368,284; 6,398,728; and 6,440,066, which are hereby incorporated herein by reference. 
     In the embodiment of the cardiac pacemaker/defibrillator  900  illustrated in  FIG. 3 , electrodes RA-tip  856 , RA-ring  854 , RV-tip  812 , RV-ring  811 , RV-coil  814 , SVC-coil  816 , LV distal electrode  813 , LV proximal electrode  817 , LA distal electrode  818 , LA proximal electrode  815 , indifferent electrode  908 , and can electrode  909  are coupled through a switch matrix  910  to sensing circuits  931 - 937 . 
     A right atrial sensing circuit  931  serves to detect and amplify electrical signals from the right atrium of the heart. Bipolar sensing in the right atrium may be implemented, for example, by sensing voltages developed between the RA-tip  856  and the RA-ring  854 . Unipolar sensing may be implemented, for example, by sensing voltages developed between the RA-tip  856  and the can electrode  909 . Outputs from the right atrial sensing circuit are coupled to the control system  920 . 
     A right ventricular sensing circuit  932  serves to detect and amplify electrical signals from the right ventricle of the heart. The right ventricular sensing circuit  932  may include, for example, a right ventricular rate channel  933  and a right ventricular shock channel  934 . Right ventricular cardiac signals sensed through use of the RV-tip  812  electrode are right ventricular near-field signals and are denoted RV rate channel signals. A bipolar RV rate channel signal may be sensed as a voltage developed between the RV-tip  812  and the RV-ring  811 . Alternatively, bipolar sensing in the right ventricle may be implemented using the RV-tip electrode  812  and the RV-coil  814 . Unipolar rate channel sensing in the right ventricle may be implemented, for example, by sensing voltages developed between the RV-tip  812  and the can electrode  909 . 
     Right ventricular cardiac signals sensed through use of the defibrillation electrodes are far-field signals, also referred to as RV morphology or RV shock channel signals. More particularly, a right ventricular shock channel signal may be detected as a voltage developed between the RV-coil  814  and the SVC-coil  816 . A right ventricular shock channel signal may also be detected as a voltage developed between the RV-coil  814  and the can electrode  909 . In another configuration the can electrode  909  and the SVC-coil electrode  816  may be electrically shorted and a RV shock channel signal may be detected as the voltage developed between the RV-coil  814  and the can electrode  909 /SVC-coil  816  combination. 
     Left atrial cardiac signals may be sensed through the use of one or more left atrial electrodes  815 ,  818 , which may be configured as epicardial electrodes. A left atrial sensing circuit  935  serves to detect and amplify electrical signals from the left atrium of the heart. Bipolar sensing and/or pacing in the left atrium may be implemented, for example, using the LA distal electrode  818  and the LA proximal electrode  815 . Unipolar sensing and/or pacing of the left atrium may be accomplished, for example, using the LA distal electrode  818  to can vector  909  or the LA proximal electrode  815  to can vector  909 . 
     A left ventricular sensing circuit  936  serves to detect and amplify electrical signals from the left ventricle of the heart. Bipolar sensing in the left ventricle may be implemented, for example, by sensing voltages developed between the LV distal electrode  813  and the LV proximal electrode  817 . Unipolar sensing may be implemented, for example, by sensing voltages developed between the LV distal electrode  813  or the LV proximal electrode  817  and the can electrode  909 . 
     Optionally, an LV coil electrode (not shown) may be inserted into the patient&#39;s cardiac vasculature, e.g., the coronary sinus, adjacent the left heart. Signals detected using combinations of the LV electrodes,  813 ,  817 , LV coil electrode (not shown), and/or can electrodes  909  may be sensed and amplified by the left ventricular sensing circuitry  936 . The output of the left ventricular sensing circuit  936  is coupled to the control system  920 . 
     The outputs of the switching matrix  910  may be operated to couple selected combinations of electrodes  811 ,  812 ,  813 ,  814 ,  815 ,  816 ,  817 ,  818 ,  856 ,  854  to an evoked response sensing circuit  937 . The evoked response sensing circuit  937  serves to sense and amplify signals developed using various combinations of electrodes for discrimination of various cardiac responses to pacing in accordance with embodiments of the invention. The cardiac response classification processor  925  may cooperate with detection window circuitry  926  to analyze the output of the evoked response sensing circuit  937  for implementation of multi-chamber cardiac pacing response classification. 
     Various combinations of pacing and sensing electrodes may be utilized in connection with pacing and sensing the cardiac signal following the pace pulses to determine the cardiac response to the pacing pulse. The pacemaker control circuit  922 , in combination with pacing circuitry for the left atrium, right atrium, left ventricle, and right ventricle  941 ,  942 ,  943 ,  944 , may be implemented to selectively generate and deliver pacing pulses to the heart using various electrode combinations. The pacing electrode combinations may be used to effect bipolar or unipolar pacing pulses to a heart chamber using one of the pacing vectors as described above. 
     In some implementations, the cardiac pacemaker/defibrillator  900  may include a sensor  961  that is used to sense the patient&#39;s hemodynamic need. In one implementation, the sensor may comprise, for example, an accelerometer configured to sense patient activity. In another implementation, the sensor may comprise an impedance sensor configured to sense patient respiration. The pacing output of the cardiac pacemaker/defibrillator may be adjusted based on the sensor output. 
     The electrical signal following the delivery of the pacing pulses may be sensed through various sensing vectors coupled through the switch matrix  910  to the evoked response sensing circuit  937  and/or other sensing circuits and used to classify the cardiac response to pacing. The cardiac response may be classified as one of left chamber capture only, right chamber capture only, multi-chamber capture, fusion and non-capture, for example. 
     Subcutaneous electrodes may provide additional sensing vectors useable for cardiac response classification. In one implementation, cardiac rhythm management system may involve a hybrid system including an intracardiac device configured to pace the heart and an extracardiac device, e.g., a subcutaneous defibrillator, configured to perform functions other than pacing. The extracardiac device may be employed to detect and classify cardiac response to pacing based on signals sensed using subcutaneous electrode arrays. The extracardiac and intracardiac devices may operate cooperatively with communication between the devices occurring over a wireless link, for example. Examples of subcutaneous electrode systems and devices are described in commonly owned U.S. Publication Nos. 2004/0230229 and 2004/0230230, which are hereby incorporated herein by reference in their respective entireties. 
       FIG. 4  is a flowchart illustrating a multi-chamber capture method in accordance with the present invention as applied to a bi-ventricular pacing embodiment. Detection windows are provided  402 , each detection window corresponding to an expected feature of the cardiac signal under conditions of LV capture, RV capture or bi-ventricular capture. The detection windows may be provided based on clinical data taken from a number of patients or may be formed based on data taken from the patient. 
     In one implementation, detection windows associated with a particular capture condition may be formed by measuring a number of cardiac signals of the patient under the particular capture condition, extracting one or more features from each of the cardiac signals, clustering the features, and determining detection window boundaries based on the clustered features. In one implementation, the features extracted and clustered comprise positive and negative cardiac signal peaks. Forming detection windows based on clustering is described in commonly owned U.S. Pat. No. 7,499,751, which is hereby incorporated herein by reference. The one or more detection windows used for detecting the particular capture condition form a detection template. Detection windows and templates comprising one or more detection windows for each capture condition (LV capture, RV capture, and bi-ventricular capture) may be formed using the clustering approach or other methods. 
     In some cases, pacing the ventricles based on tracked atrial events is used to more closely mimic the patient&#39;s natural rhythm. During a cardiac cycle, an atrial pacing pulse is delivered to the atrium or atrial activity is sensed  404 . An atrioventricular (AV) delay is initiated  406  relative to the sensed or paced atrial event. The AV delay may have a predetermined, programmable, or automatically adjustable duration. 
     Maintaining consistent bi-ventricular pacing enhances cardiac resynchronization. The AV delay may be set to a relatively short duration relative to the patient&#39;s AV conduction time to promote bi-ventricular pacing. 
     The first and second ventricles may be paced substantially simultaneously or in phased sequence. In one implementation, a first ventricle (left or right) is paced  408  relative to the AV delay and the second ventricle (right or left) is paced  410  relative an interventricular (IV) delay. The interventricular delay may be a fixed, programmable, or automatically adjustable duration. 
     The sensing channel used for capture detection, e.g., evoked response channel, is blanked  412  after the ventricular paces. For example, the evoked response channel may be blanked during the interventricular delay and for about 0 milliseconds to about 40 milliseconds after the last ventricular pace. After blanking, the cardiac signal is sensed  414 . The cardiac signal comprises a cardiac electrogram signal that may be sensed using one or more electrodes positioned within one or more heart chambers and/or within one or more veins of the heart. In this implementation, the cardiac electrogram signal may be sensed using an electrode positioned in the right ventricle (RV tip electrode, RV ring electrode or RV coil electrode), an electrode positioned within a vein of the left ventricle (LV distal electrode or LV proximal electrode), and/or electrodes positioned in the right ventricle and the left ventricular vein, for example. The cardiac signal is compared to an activity detection threshold (ADT) which comprises positive and negative thresholds. If the cardiac signal does not exceed  416  the ADT in either the positive or negative direction, then the cardiac response is determined  418  to be a non-captured response. If non-capture is detected,  418  a back up pace may be delivered  420  to one or both ventricles. 
     If the cardiac signal exceeds  416  the ADT, the cardiac signal morphology is compared to the expected morphology associated with various capture conditions. Cardiac signal features are extracted and compared to detection windows comprising a template associated with a particular type of capture condition. Cardiac signal features may be compared  422  to one or more of a template associated with bi-ventricular capture, a template associated with LV capture and a template associated with RV capture. 
     In one implementation, the extracted features of the cardiac signal may comprise positive and negative peaks. The amplitude and timing of the cardiac signal peaks may be compared to expected peak amplitudes and peak times associated with capture conditions LV capture, RV capture, and/or bi-ventricular capture. 
     If the cardiac signal peaks fall within one or more detection windows associated with LV capture, then the capture condition is determined  426  to be LV capture. If the cardiac signal peaks fall within one or more detection windows associated with RV capture, then the capture condition is determined  424  to be RV capture. If the cardiac signal peaks fall within on or more detection windows associated with bi-ventricular capture, then the capture condition is determined  428  to be bi-ventricular capture. If the cardiac signal peaks do not fall within any of the detection windows, or if the cardiac signal peaks fall within multiple detection windows representing different capture conditions, then the capture condition may be determined to be fusion. 
     If the features of the cardiac signal are consistent with a particular capture template, then the particular capture template may be updated  430  using the features. Methods and systems for updating cardiac pacing response templates are described in commonly owned U.S. Pat. No. 7,574,260, which is hereby incorporated herein by reference. 
       FIG. 5  provides a composite graph of signals representative of bi-ventricular capture  510  and of signals representative of RV capture only (LV non-capture)  520 . These signals follow pacing pulses delivered to the right and left ventricles. A signal similar to the bi-ventricular capture signals  510  is produced when the pacing pulses capture both ventricles. A signal similar to the RV capture signals  520  is produced when the pacing pulse delivered to the right ventricle captures the right ventricle and the pacing pulse delivered to the left ventricle does not capture the left ventricle. 
     Both the bi-ventricular capture signals  510  and the RV capture signals  520  have an initial peak followed by a peak of opposite polarity. However, the signals  510 ,  520  differ in morphology. As can be seen from  FIG. 5 , the morphology of the signals  520  associated with RV only capture have slightly wider peak widths and the peaks are delayed in time when compared to the signals  510  associated with bi-ventricular capture. 
     The morphological differences between signals associated with bi-ventricular capture  510  and signals associated with RV capture  520  can be utilized to discriminate between bi-ventricular capture and RV capture.  FIG. 5  illustrates detection windows  512 ,  514   522 ,  524  that may be used to discriminate between bi-ventricular capture and RV capture. 
     First  512  and second  514  bi-ventricular detection windows are used to detect bi-ventricular capture. If the positive peak of a cardiac signal falls within the first bi-ventricular detection window  512  and the negative peak of the cardiac signal falls within the second bi-ventricular detection window  514 , then the system determines that both the left and the right ventricles were captured by the pacing pulses. 
     If the positive peak of the cardiac signal falls in the first RV capture detection window  522  and the negative peak of the cardiac signal falls in the second RV capture detection window  524 , then the system determines that the pacing pulse delivered to the right ventricle captured the right ventricle and the pacing pulse delivered to the left ventricle did not capture the left ventricle. If the positive or negative value of the cardiac signal does not exceed the ADT  505 , then neither ventricle was captured. If the cardiac signal peaks do not fall within any of the detection windows, or if the cardiac signal peaks fall within multiple detection windows representing the two capture conditions, then the capture condition may be determined to be fusion. 
       FIG. 6  provides a composite graph of signals representative of bi-ventricular capture  610  and of signals representative of LV capture only (RV non-capture)  620 . These signals follow pacing pulses delivered to the right and left ventricles. A signal similar to the bi-ventricular capture signals  610  is produced when the pacing pulses capture both ventricles. A signal similar to the LV capture signals  620  is produced when the pacing pulse delivered to the left ventricle captures the left ventricle and the pacing pulse delivered to the right ventricle does not capture the right ventricle. 
     As can be seen from  FIG. 6 , the signals associated with LV capture  620  have peaks that are inverted and delayed in time when compared to the signals associated with bi-ventricular capture  610 . The morphological differences between signals associated with bi-ventricular capture and signals associated with LV capture can be utilized to discriminate between bi-ventricular capture and LV capture.  FIG. 6  illustrates detection windows  612 ,  614 ,  622  that may be used to discriminate between bi-ventricular capture and LV capture. 
     First  612  and second  614  bi-ventricular detection windows are used to detect bi-ventricular capture. If the positive peak of a cardiac signal falls within the first bi-ventricular detection window  612  and the negative peak of the cardiac signal falls within the second bi-ventricular detection window  614 , then the system determines that both the left and the right ventricles were captured by the pacing pulses. 
     If the positive peak of the cardiac signal falls in the LV capture detection window  622  then the system determines that the pacing pulse delivered to the left ventricle captured the left ventricle and the pacing pulse delivered to the right ventricle did not capture the right ventricle. If the amplitude of the cardiac signal does not exceed the ADT  605 , in either the positive or negative direction, then neither ventricle was captured. If the cardiac signal peaks do not fall within any of the detection windows, or if the cardiac signal peaks fall within multiple detection windows representing the two capture conditions, then the capture condition may be determined to be fusion. 
     By way of example, the processes of the present invention may be used to enhance capture threshold testing to determine a suitable energy for pacing. Determination of a suitable pacing energy may be implemented, for example, by an automatic capture threshold testing procedure executed by an implantable pacemaker/defibrillator or other cardiac rhythm management device. Additionally, automatic capture verification may be used, for example, to monitor capture on a beat-by-beat basis. Automatic capture verification may be used to control back up pacing when a pace pulse delivered to the heart fails to evoke a captured response. These and other applications may be enhanced by the multi-chamber capture approaches of the present invention. 
     Those skilled in the art will appreciate that reference to a capture threshold testing procedure indicates a method of determining the capture threshold in one or more of the left atrium, the right atrium, both the left atrium and the right atrium, the left ventricle, the right ventricle, and/or both the left ventricle and the right ventricle. In such a procedure, the pacemaker, automatically or upon command, initiates a search for the capture threshold of the selected heart chamber or chambers. The capture threshold is defined as the lowest pacing energy that consistently produces a contraction of the heart chamber. 
     In one example of an automatic capture threshold procedure, the pacemaker delivers a sequence of pacing pulses to the heart chamber or chambers and detects the cardiac responses to the pace pulses. The energy of the pacing pulses may be decreased in discrete steps until a predetermined number of loss-of-capture events occur. After the predetermined number of loss-of-capture events occur, the pacemaker may increase the stimulation energy in discrete steps until a predetermined number of capture events occur to confirm the capture threshold. A capture threshold test may be performed using the multi-chamber capture detection approaches of the present invention. 
     Other procedures for implementing capture threshold testing may be utilized. In one example, the pacing energy may be initially set to zero or a relatively low pacing energy and then increased in discrete steps until capture is detected. In another example, the pacing energy may be adjusted according to a binomial search pattern. 
     Automatic capture threshold determination is distinguishable from automatic capture verification, a procedure that may occur on a beat-by-beat basis during pacing. Automatic capture verification verifies that a delivered pace pulse results in a captured response. When a captured response is not detected following a pace pulse, the pacemaker may deliver a back up safety pace to ensure consistent pacing. The back up pace may be delivered, for example, about 90-110 ms after the initial pace pulse. If a predetermined number of pace pulses delivered during normal pacing do not produce a captured response, the pacemaker may initiate a capture threshold test to determine the capture threshold. Automatic capture verification and back up pacing may be implemented using the multi-chamber capture detection processes of the present invention. 
       FIG. 7  illustrates an automatic capture threshold testing procedure for multi-chamber pacing using multi-chamber capture detection in accordance with approaches of the invention. The pacing energy of first and second heart chambers is initialized  710  to a value exceeding the capture threshold, such as a maximum pacing value. Blocks  715 - 730  illustrate a method of incrementally decreasing  715  the pacing energy of the first chamber until loss of capture (LOC) occurs  730 . After each incremental reduction  715  in pacing energy, the first and second chambers are paced  720 . The cardiac signal following the pacing energy is sensed  725  and compared to one or more detection windows associated with expected characteristics of multi-chamber capture and/or second chamber only capture and/or first chamber only capture. If the signal characteristics are consistent with second chamber only capture, then loss of capture of the first chamber is detected  730 . The first chamber energy value is stored  735  as the first chamber capture threshold. 
     The pacing energy of the first chamber is reinitialized  740  to a value exceeding the capture threshold. Blocks  745 - 755  illustrate a method of incrementally decreasing  745  the pacing energy of the second chamber until loss of capture (LOC) occurs  755 . After each incremental reduction  745  in pacing energy, the first and second chambers are paced  750 . The cardiac signal following the pacing energy is sensed  752  and compared to one or more detection windows associated with expected characteristics of multi-chamber capture and/or second chamber only capture and/or first chamber only capture. If the signal characteristics are consistent with first chamber only capture, then loss of capture of the second chamber is detected  755 . The second chamber energy value is stored  760  as the second chamber capture threshold. 
     In some embodiments, a first electrogram signal may be used to determine the capture condition and one or more additional electrogram signals may be used to confirm or increase a level of confidence in the capture determination. In some implementations, the first electrogram signal may be sensed using an electrode electrically coupled to a first heart chamber and an additional electrogram signal may be sensed using an electrode electrically coupled to a second heart chamber. In some implementations, the first and additional electrogram signals may be sensed using electrodes electrically coupled to the same chamber. 
     The processor may evaluate the first and additional cardiac electrogram signals to distinguish capture conditions in various combinations. For example, the processor may evaluate the first signal to discriminate between a first two of right chamber capture only, left chamber capture only, and multi-chamber capture to determine the capture condition. The processor may use an additional signal to distinguish between a second two of right chamber capture only, left chamber capture only, and multi-chamber capture to confirm the capture condition. Distinguishing between other combinations of capture conditions including left chamber capture only, right chamber capture only, multi-chamber capture, non-capture, and fusion for capture confirmation is possible. 
     A process of using an additional electrocardiogram signal for confirming capture determination is illustrated by the flowchart of  FIG. 8 . Pacing pulses are delivered  1010  to left and right heart chambers during a cardiac cycle. A first electrogram signal is sensed  1020 , for example, using an electrode associated with a first heart chamber. A second electrocardiogram is sensed  1030 , for example, using an electrode associated with a second heart chamber. The capture condition is determined  1040  using the first signal. The second signal is used to confirm  1050  or increase confidence in the capture condition determination. 
     In some embodiments, a selected electrode may be used to determine the capture condition. The selection may be based on parameters of the signal produced using the electrode, including, for example, signal integrity (signal to noise ratio), suitability for capture detection, sensitivity to a particular capture condition, e.g., LV capture or bi-ventricular capture, over sense condition, lead impedance outside a predetermined range, capture amplitude voltage outside a predetermined range, intrinsic amplitude outside a predetermined range, detection of unintended non-cardiac stimulation, failure to detect an expected event and/or other parameters of the signal.  FIGS. 9A and 9B  are flowcharts illustrating electrode selection processes in accordance with embodiments of the invention. 
       FIGS. 9A and 9B  illustrate methods of selecting capture sensing electrodes for use in automatic capture threshold testing and/or beat to beat automatic capture verification. The process illustrated in  FIG. 9A  may be particularly suited, for example, for use in connection with an automatic capture threshold test. Prior to beginning the test, the signals produced by available electrode combinations are evaluated  1101  with respect to signal to noise ratio and/or other parameters associated with capture detection suitability as described above. An electrode combination is selected  1105  for capture detection during the test. Pacing pulses are delivered  1110  to left and right heart chambers. The cardiac signal is sensed  1115  using the selected electrode combination. The capture condition is determined  1120  based on characteristics of the sensed signal. 
     The capture determination process illustrated by the flowchart of  FIG. 9B  may be used, for example, to select between available electrode combinations in beat to beat automatic capture verification, and/or other capture detection processes. The illustrated process allows the pacemaker to switch between capture sensing electrodes if the signal from a particular electrode combination becomes noisy or produces unreliable capture results. An initial electrode combination is selected  1125  for capture sensing. Pacing pulses are delivered  1130  to the left and right heart chambers. A cardiac electrogram signal is sensed  1135  using the selected electrode combination. If the signal is suitable  1140  for capture detection, e.g., not noisy, minimum signal level, etc., then the capture condition is determined  1150  based on the signal characteristics. If the signal is unsuitable  1140  for capture detection, particularly if the signal is persistently unsuitable, then the system may select  1145  a different electrode combination. Methods and systems for selective use of various electrode combinations to improve capture detection and other pacemaker/defibrillator functions, aspects of which may be utilized in connection with the present invention, are described in commonly owned U.S. Pat. No. 6,493,586 which is incorporated herein by reference. 
     The components, functionality, and structural configurations depicted herein are intended to provide an understanding of various features and combination of features that may be incorporated in an implantable pacemaker/defibrillator. It is understood that a wide variety of cardiac monitoring and/or stimulation device configurations are contemplated, ranging from relatively sophisticated to relatively simple designs. As such, particular cardiac device configurations may include particular features as described herein, while other such device configurations may exclude particular features described herein. 
     Various modifications and additions can be made to the preferred embodiments discussed hereinabove without departing from the scope of the present invention. Accordingly, the scope of the present invention should not be limited by the particular embodiments described above, but should be defined only by the claims set forth below and equivalents thereof.