Abstract:
According to this disclosure, a non-transvenous pacing and, optionally defibrillation, therapy device is implanted subcutaneously and oriented to provide cardiac sensing from electrodes spaced from a heart and deliver pacing and/or defibrillation from one or more non-transvenous electrodes (e.g., an epicardial or pericardial electrode or electrode patch). A subject receiving a device according to this disclosure is monitored to confirm a relatively stable bundle branch block (i.e., delayed activation) of one ventricle. The subcutaneous device has electrodes disposed on the housing and/or having an electrode on a subcutaneous medical lead is oriented so that the pacing (and sensing) vector impinges mainly upon the one ventricle, and/or optionally an epicardial or pericardial lead is deployed to a last-to-depolarize ventricle (e.g., a left ventricle) so that single-ventricular pacing is delivered to achieve fusion depolarization of both ventricles.

Description:
CROSS REFERENCE AND STATEMENT OF INCORPORATION 
       [0001]    This patent application relates to co-pending application Ser. No. 11/343,677 filed 31 Jan. 2006 entitled, “SUBCUTANEOUS ICD WITH SEPARATE CARDIAC RHYTHM SENSOR,” the entire contents of each is hereby incorporated by reference herein. 
     
    
     FIELD 
       [0002]    The disclosure pertains to cardiac resynchronization therapy (CRT) delivery pacing systems that efficiently deliver fusion-based CRT via ventricular pre-excitation from electrodes spaced from the heart. 
       BACKGROUND 
       [0003]    It has been shown that in certain patients exhibiting symptoms resulting from congestive heart failure (CHF), cardiac output is enhanced by timing the delivery of a left ventricular (LV) pacing pulse, via a lead disposed in a portion of the great cardiac vein, evoked depolarization of the LV is effected in fusion with the intrinsic depolarization of the right ventricle (RV). The fusion depolarization enhances stroke volume in such hearts where the RV depolarizes first due to intact atrio-ventricular (AV) conduction of a preceding intrinsic or evoked atrial depolarization wave front, but wherein the AV conducted depolarization of the LV is unduly delayed. The fusion depolarization of the LV is attained by timing the delivery of the LV pace (LVp) pulse to follow the intrinsic depolarization of the RV but to precede the intrinsic depolarization of the LV. Specifically, an RV pace (RVp) pulse is not delivered due to the inhibition of the RVp event upon the sensing of RV depolarization (RVs), allowing natural propagation of the wave front and depolarization of the intraventricular septum, while an LVp pulse is delivered in fusion with the RV depolarization. 
         [0004]    However, due to a number of factors (e.g., the amount of time required for appropriate signal processing, confounding conduction delays or conduction blockage of a patient, diverse electrode placement locations, and the like) for a variety of patients the system described may not always effectively deliver CRT. Also, the cost and complexity programming and implanting triple-chamber devices confounds many clinicians and patients in obtaining chronic CRT delivery. 
         [0005]    A need therefore exists in the art to simply, efficiently and chronically deliver CRT to patients suffering from various cardiac conduction abnormalities who might not otherwise receive the benefits of CRT therapy. 
       SUMMARY 
       [0006]    According to this disclosure, a non-transvenous pacing and, optionally defibrillator device is implanted subcutaneously and oriented to provide pacing therapy from electrodes spaced from a heart. A subject receiving a device according to this disclosure is monitored to confirm a relatively stable bundle branch block or delayed activation of one ventricle. The subcutaneous device having electrodes disposed on the housing and/or having an electrode on a subcutaneous medical lead is oriented so that the pacing (and sensing) vector impinges mainly upon the one ventricle. 
         [0007]    A single pacing stimulus is then delivered upon expiration of an AV interval timed from at least one prior intrinsic atrial event, represented herein as “As” determined from at least one prior As that resulted in an intrinsic sensed ventricular event (Vs). The triggering event, Ap, can emanate from the right atrium (RA) or the left atrium (LA) and the “single” ventricular pacing stimulus is timed to pre-excite the one ventricle so that intra-ventricular mechanical synchrony results. The mechanical synchrony results from the fusing of the two ventricular depolarization wavefronts (i.e., one “paced” and the other more or less intrinsically-conducted). 
         [0008]    Accordingly, delivery of a single “ventricular” pacing stimulus occurs upon expiration of a fusion-AV or, herein referred to as the pre-excitation interval (“PEI”). One way to express this relationship defines the PEI as being based on an intrinsic AV interval or intervals from an immediately prior cardiac cycle or cycles. Thus, the PEI can be expressed as PEI=AV n-1 −V pei , wherein the AV interval represents the interval from an A-event (As) to the resulting intrinsic depolarization of a ventricle (for a prior cardiac cycle) and the value of PEI equals the desired amount of pre-excitation needed to effect ventricular fusion (expressed in ms). For a patient with LBBB conduction status (for a current cardiac cycle “n”) the above formula can be expressed as: A-LVp n =A-RV n-1 −LV pei  and for a patient suffering from RBBB conduction status the formula reduces to: A-RVp n =A-LV n-1 −RV pei . 
         [0009]    As noted above, the timing of the single pacing stimulus is an important parameter when delivering therapy according to the foregoing. While a single, immediately prior atrial event (Ap) to a RV or an LV sensed depolarization can be utilized to set the PEI and derive the timing for delivering pacing stimulus (i.e., A-RV n-1  or A-LV n-1 ) more than a single prior sensed AV interval, a prior PEI, a plurality of prior sensed AV intervals or prior PEIs can be utilized (e.g., mathematically calculated values such as a temporal derived value, a mean value, an averaged value, a median value and the like). Also, a time-weighted value of the foregoing can be employed wherein the most recent values receive additional weight. Alternatively, the PEI can be based upon heart rate (HR), a derived value combining HR with an activity sensor input, P-wave to P-wave timing, R-wave to R-wave timing and the like. Again, these values may be time-weighted in favor of the most, or more, recent events. Of course, other predictive algorithms could be used which would account for variability, slope or trend in AV interval timing and thereby predict AV characteristics. 
         [0010]    Among other aspects, this provides ah energy-efficient manner of providing single ventricle, pre-excitation fusion-pacing therapy delivered from a non-transvenously implanted medical device. 
         [0011]    Since an evoked depolarization from electrodes spaced remotely from the heart excites the myocardium from the opposite side of the ventricular wall (versus normal intrinsic cardiac excitation), the LV may heed to be excited before an intrinsic sense (RVs) occurs for the same cycle to achieve optimal performance. 
         [0012]    In another aspect, in lieu of delivering the therapy from electrodes spaced from the heart a single epicardial pacing lead and optionally, a defibrillation electrode or array, is deployed into contact with the last-to-depolarize ventricle. The implant procedure for an extra-cardiac ICD (e.g. sub-Q or sub-muscular) used to practice the foregoing—in the pectoral region—allows for chronic application of CRT. Preexisting LV implant leads and tools have been developed that make sub-xiphoid implants on the epicardium feasible. The challenge with obtaining CRT by simply placing a lead on the LV is that proper CRT can only be delivered if the LV pace is timed to the intrinsic atrial and/or ventricular activity. This disclosure describes methods to allow for BiV, Triggered and Fusion CRT with an EC-ICD system. The primary embodiment of the disclosure is a single lead extra-vascular system, with the lead placed on the LV. Fusion based CRT could be delivered by sensing far-field atrial signals (P-waves) and far-field ECG to determine earliest activation. Fusion pacing algorithms whose basic concepts have already been disclosed could then be applied, monitoring A-RVs times and pacing the LV at shorter A-LVp intervals. A triggered pacing mode could be a backup mode to fusion if reliable P-waves cannot be detected, triggering an LV pace off of a ventricular sense. Special signal processing (e.g., filtering) techniques are used to accurately determine the P-wave, including detecting an R-wave and then looking back over a window where the P-wave is detected. Additional electrode/lead locations may be used to pick up P-wave and R-wave activity, including extra-vascular leads passing around the chest to the posterior of a subject. 
         [0013]    Some features of the disclosure include the following:
   delivery of fusion pacing via a single LV lead using far-field sensing of the P-waves.   Computation of a Fusion A-V (F-A-V) interval based on a periodic evaluation of a P-R interval and the use of a pre-excitation interval (PEI).   Titration of the PEI or detection point on the P-wave based on the resulting paced fusion beat.   A mode switch from Fusion to triggered pacing if P-waves cannot be reliably detected.   The lead attached to the heart could include defibrillation coils to assist in lowering DFTs.   Addition of an RV lead to deliver BiV pacing.   
 
         [0020]    The foregoing and other aspects and features of the present disclosure will be more readily understood from the following detailed description of the embodiments thereof, when considered in conjunction with the drawings which like reference numerals indicate similar structures throughout the several views, and with reference to the claims appearing at the end of this disclosure. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0021]      FIG. 1  is a schematic diagram of an exemplary subcutaneous device in which the present disclosure may be usefully practiced. 
           [0022]      FIG. 2  is a perspective view of a system according to certain embodiments of the disclosure. 
           [0023]      FIG. 3A  is an exemplary schematic diagram of electronic circuitry within a hermetically sealed housing of a subcutaneous device of the present disclosure. 
           [0024]      FIG. 3B  is a schematic diagram of signal processing aspects of a subcutaneous device according to an exemplary embodiment of the present disclosure. 
           [0025]      FIG. 3C  is a schematic diagram of a rectifier and auto-threshold unit in a subcutaneous device according to an embodiment of the present disclosure. 
           [0026]      FIG. 4  illustrates an embodiment of the energy efficient, single-pacing stimulus, ventricular pre-excitation pacing mode according to the present disclosure. 
           [0027]      FIG. 5  illustrates an embodiment of the energy efficient, single-pacing stimulus, ventricular pre-excitation pacing mode according to the present disclosure. 
           [0028]      FIG. 6  depicts a process for periodically ceasing delivery of the pre-excitation, single ventricular pacing therapy to determine the cardiac conduction status of a patient and performing steps based on the status. 
       
    
    
     DETAILED DESCRIPTION 
       [0029]    In the following detailed description, references are made to illustrative embodiments for carrying out an energy efficient, single-pacing stimulus, ventricular pre-excitation pacing mode according to the present disclosure. It is understood that other embodiments may be utilized without departing from the scope of the disclosure. For example, examples are disclosed in detail herein in the context of an intrinsically-based or AV sequential (evoked) uni-ventricular pacing system with remote ventricular sensing. This provides an efficient pacing modality for restoring electromechanical ventricular synchrony based upon either atrial-paced or atrial-sensed events particularly for patients with some degree of either chronic, acute or paroxysmal ventricular conduction block (e.g., intraventricular, LBBB, RBBB). A system according to the disclosure efficiently can provide cardiac resynchronization therapy (CRT) with a single pacing stimulus per cardiac cycle. 
         [0030]    The following issued U.S. patents are hereby incorporated into this disclosure as if fully set forth herein; namely, U.S. Pat. No. 6,871,096 to Hill, entitled, “System and Method for Bi-Ventricular Fusion-pacing;” issued U.S. Pat. No. 7,254,442 to Pilmeyer and van Gelder entitled, “APPARATUS AND METHODS FOR ‘LEPARS’ INTERVAL-BASED FUSION-PACING;” and U.S. Pat. No. 7,181,284 to Burnes and Mullen entitled, “APPARATUS AND METHODS OF ENERGY EFFICIENT, ATRIAL-BASED BI-VENTRICULAR FUSION-PACING.” 
         [0031]      FIG. 1  is a schematic diagram of an exemplary subcutaneous device in which the present disclosure may be usefully practiced. As illustrated in  FIG. 1 , a subcutaneous device  14  according to an embodiment of the present disclosure is subcutaneously implanted outside the ribcage of a patient  12 , anterior to the cardiac notch. Further, a subcutaneous sensing and cardioversion/defibrillation therapy delivery lead  18  in electrical communication with subcutaneous device  14  is tunneled subcutaneously into a location adjacent to a portion of a latissimus dorsi muscle of patient  12 . Specifically, lead  18  is tunneled subcutaneously from the median implant pocket of the subcutaneous device  14  laterally and posterially to the patient&#39;s back to a location opposite the heart such that the heart  16  is disposed between the subcutaneous device  14  and the distal electrode coil  24  and distal sensing electrode  26  of lead  18 . 
         [0032]    It is understood that while the subcutaneous device  14  is shown positioned through loose connective tissue between the skin and muscle layer of the patient, the term “subcutaneous device” is intended to include a device that can be positioned in the patient to be implanted using any non-intravenous location of the patient, such as below the muscle layer or within the thoracic cavity, for example. 
         [0033]    Further referring to  FIG. 1 , a programmer  20  is shown in telemetric communication with subcutaneous device  14  by an RF communication link  22 . Communication link  22  may be any appropriate RF link such as Bluetooth, WiFi, MICS, or as described in U.S. Pat. No. 5,683,432 “Adaptive Performance-Optimizing Communication System for Communicating with an Implantable Medical Device” to Goedeke, et al. and incorporated herein by reference in its entirety. 
         [0034]    Subcutaneous device  14  includes a housing  15  that may be constructed of stainless steel, titanium or ceramic as described in U.S. Pat. No. 4,180,078 “Lead Connector for a Body implantable Stimulator” to Anderson and U.S. Pat. No. 5,470,345 “Implantable Medical Device with Multi-layered Ceramic Enclosure” to Hassler, et al, both incorporated herein by reference in their entireties. The electronics circuitry of SubQ ICD  14  may be incorporated on a polyimide flex circuit, printed circuit board (PCB) or ceramic substrate with integrated circuits packaged in leadless chip carriers and/or chip scale packaging (CSP). 
         [0035]    Subcutaneous lead  18  includes a distal defibrillation coil electrode  24 , a distal sensing electrode  26 , an insulated flexible lead body and a proximal connector pin  27  (shown in  FIG. 2 ) for connection to the housing  15  of the subcutaneous device  14  via a connector  25 . In addition, one or more electrodes  28  (shown in  FIG. 2 ) are positioned along the outer surface of the housing to form a housing-based subcutaneous electrode array (SEA). Distal sensing electrode  26  is sized appropriately to match the sensing impedance of the housing-based subcutaneous electrode array. 
         [0036]    It is understood that while device  14  is shown with electrodes  28  positioned on housing  15 , according to an embodiment of the present disclosure electrodes  28  may be alternatively positioned along one or more separate leads connected to device  14  via connector  25 . 
         [0037]    Continuing with  FIG. 2 , electrodes  28  are welded into place on the flattened periphery of the housing  15 . In the embodiment depicted in this figure, the complete periphery of the SubQ ICD may be manufactured to have a slightly flattened perspective with rounded edges to accommodate the placement of the electrodes  28 . The electrodes  28  are welded to housing  15  (to preserve hermaticity) and are connected via wires (not shown) to electronic circuitry (described herein below) inside housing  15 . Electrodes  28  may be constructed of flat plates, or alternatively, may be spiral electrodes as described in U.S. Pat. No. 6,512,940 “Subcutaneous Spiral Electrode for Sensing Electrical Signals of the Heart” to Brabec, et al. and mounted in a non-conductive surround shroud as described in U.S. Pat. No. 6,522,915 “Surround Shroud Connector and Electrode Housings for a Subcutaneous Electrode Array and Leadless ECGs” to Ceballos, et al. and U.S. Pat. No. 6,622,046 “Subcutaneous Sensing Feedthrough/Electrode Assembly” to Fraley, et al, all incorporated herein by reference in their entireties. The electrodes  28  of  FIG. 2  can be positioned to form orthogonal or equilateral signal vectors, for example. 
         [0038]    The electronic circuitry employed in subcutaneous device  14  can take any of the known forms that detect a tachyarrhythmia from the sensed ECG and provide cardioversion/defibrillation shocks as well as post-shock pacing as needed while the heart recovers. A simplified block diagram of such circuitry adapted to function employing the first and second cardioversion-defibrillation electrodes as well as the ECG sensing and pacing electrodes described herein below is set forth in  FIG. 3A . It will be understood that the simplified block diagram does not show all of the conventional components and circuitry of such devices including digital clocks and clock lines, low voltage power supply and supply lines for powering the circuits and providing pacing pulses or telemetry circuits for telemetry transmissions between the device  14  and external programmer  20 . 
         [0039]      FIG. 3A  is an exemplary schematic diagram of electronic circuitry within a hermetically sealed housing of a subcutaneous device according to an embodiment of the present disclosure. As illustrated in  FIG. 3A , subcutaneous device  14  includes a low voltage battery  153  coupled to a power supply (not shown) that supplies power to the circuitry of the subcutaneous device  14  and the pacing output capacitors to supply pacing energy in a manner well known in the art. The low voltage battery  153  may be formed of one or two conventional LiCF x , LiMnO 2  or LiI 2  cells, for example. The subcutaneous device  14  also includes a high voltage battery  112  that may be formed of one or two conventional LiSVO or LiMnO 2  cells. Although two both low voltage battery and a high voltage battery are shown in  FIG. 3A , according to an embodiment of the present disclosure, the device  14  could utilize a single battery for both high and low voltage uses. 
         [0040]    Further referring to  FIG. 3A , subcutaneous device  14  functions are controlled by means of software, firmware and hardware that cooperatively monitor the ECG, determine when a cardioversion-defibrillation shock or pacing is necessary, and deliver prescribed cardioversion-defibrillation and pacing therapies. The subcutaneous device  14  may incorporate circuitry set forth in commonly assigned U.S. Pat. No. 5,163,427 “Apparatus for Delivering Single and Multiple Cardioversion and Defibrillation Pulses” to Keimel and U.S. Pat. No. 5,188,105 “Apparatus and Method for Treating a Tachyarrhythmia” to Keimel for selectively delivering single phase, simultaneous biphasic and sequential biphasic cardioversion-defibrillation shocks typically employing ICD IPG housing electrodes  28  coupled to the COMMON output  123  of high voltage output circuit  140  and cardioversion-defibrillation electrode  24  disposed posterially and subcutaneously and coupled to the HVI output  113  of the high voltage output circuit  140 . Outputs  132  of  FIG. 3A  is coupled to sense electrode  26 . 
         [0041]    The cardioversion-defibrillation shock energy and capacitor charge voltages can be intermediate to those supplied by ICDs having at least one cardioversion-defibrillation electrode in contact with the heart and most AEDs having cardioversion-defibrillation electrodes in contact with the skin. The typical maximum voltage necessary for ICDs using most biphasic waveforms is approximately 750 Volts with an associated maximum energy of approximately 40 Joules. The typical maximum voltage necessary for AEDs is approximately 2000-5000 Volts with an associated maximum energy of approximately 200-360 Joules depending upon the model and waveform used. The subcutaneous device  14  of the present disclosure uses maximum voltages in the range of about 300 to approximately 1000 Volts and is associated with energies of approximately 25 to 150 joules or more. The total high voltage capacitance could range from about 50 to about 300 microfarads. Such cardioversion-defibrillation shocks are only delivered when a malignant tachyarrhythmia, e.g., ventricular fibrillation is detected through processing of the far field cardiac ECG employing the detection algorithms as described herein below. 
         [0042]    In  FIG. 3A , sense amp  190  in conjunction with pacer/device timing circuit  178  processes the far field ECG sense signal that is developed across a particular ECG sense vector defined by a selected pair of the subcutaneous electrodes  24 ,  26  and  28 , or, optionally, a virtual signal (i.e., a mathematical combination of two vectors) if selected. The selection of the sensing electrode pair is made through the switch matrix/MUX  191  in a mariner to provide the most reliable sensing of the ECG signal of interest, which would be the R wave for patients who are believed to be at risk of ventricular fibrillation leading to sudden death. The far field ECG signals are passed through the switch matrix/MUX  191  to the input of the sense amplifier  190  that, in conjunction with pacer/device timing circuit  178 , evaluates the sensed EGM. Bradycardia, or asystole, is typically determined by an escape interval timer within the pacer timing circuit  178  and/or the control circuit  144 . Pace Trigger signals are applied to the pacing pulse generator  192  generating pacing stimulation when the interval between successive R-waves exceeds the escape interval. According to the disclosure, fusion-pacing therapy is delivered via this circuitry. Also, bradycardia pacing can be temporarily provided to maintain cardiac output after delivery of a cardioversion-defibrillation shock that may cause the heart to slowly beat as it recovers back to normal function. Sensing subcutaneous far field signals in the presence of noise may be aided by the use of appropriate denial and extensible accommodation periods as described in U.S. Pat. No. 6,236,882 “Noise Rejection for Monitoring ECGs” to Lee, et al. and incorporated herein by reference in its entirety. 
         [0043]    Detection of a malignant tachyarrhythmia is determined in the Control circuit  144  as a function of the intervals between R-wave sense event signals that are output from the pacer/device timing  178  and sense amplifier circuit  190  to the timing and control circuit  144 . It should be noted that the present disclosure utilizes not only interval based signal analysis method but also supplemental sensors and morphology processing method and apparatus as described herein below. 
         [0044]    Supplemental sensors such as tissue color, tissue oxygenation, respiration, patient activity and the like may be used to contribute to the decision to apply or withhold a defibrillation therapy as described generally in U.S. Pat. No. 5,464,434 “Medical Interventional Device Responsive to Sudden Hemodynamic Change” to Alt and incorporated herein by reference in its entirety. Sensor processing block  194  provides sensor data to microprocessor  142  via data bus  146 . Specifically, patient activity and/or posture may be determined by the apparatus and method as described in U.S. Pat. No. 5,593,431 “Medical Sen/ice Employing Multiple DC Accelerometers for Patient Activity and Posture Sensing and Method” to Sheldon and incorporated herein by reference in its entirety. Patient respiration may be determined by the apparatus and method as described in U.S. Pat. No. 4,567,892 “Implantable Cardiac Pacemaker” to Plicchi, et al. and incorporated herein by reference in its entirety. Patient tissue oxygenation or tissue color may be determined by the sensor apparatus and method as described in U.S. Pat. No. 5,176,137 to Erickson, et al. and incorporated herein by reference in its entirety. The oxygen sensor of the &#39;137 patent may be located in the subcutaneous device pocket or, alternatively, located on the lead  18  to enable the sensing of contacting or near-contacting tissue oxygenation or color. 
         [0045]    Certain steps in the performance of the detection algorithm criteria are cooperatively performed in microcomputer  142 , including microprocessor, RAM and ROM, associated circuitry, and stored detection criteria that may be programmed into RAM via a telemetry interface (not shown) conventional in the art. Data and commands are exchanged between microcomputer  142  and timing and control circuit  144 , pacer timing/amplifier circuit  178 , and high voltage output circuit  140  via a bi-directional data/control bus  146 . The pacer timing/amplifier circuit  178  and the control circuit  144  are clocked at a slow clock rate. The microcomputer  142  is normally asleep, but is awakened and operated by a fast clock by interrupts developed by each R-wave sense event, on receipt of a downlink telemetry programming instruction or upon delivery of cardiac pacing pulses to perform any necessary mathematical calculations, to perform tachycardia and fibrillation detection procedures, and to update the time intervals monitored and controlled by the timers in pacer/device timing circuitry  178 . 
         [0046]    When a malignant tachycardia is detected, high voltage capacitors  156 ,  158 ,  160 , and  162  are charged to a pre-programmed voltage level by a high-voltage charging circuit  164 . It is generally considered inefficient to maintain a constant charge on the high voltage output capacitors  156 ,  158 ,  160 ,  162 . Instead, charging is initiated when control circuit  144  issues a high voltage charge command HVCHG delivered on line  145  to high voltage charge circuit  164  and charging is controlled by means of bi-directional control/data bus  166  and a feedback signal VCAP from the HV output circuit  140 . High voltage output capacitors  156 ,  158 ,  160  and  162  may be of film, aluminum electrolytic or wet tantalum construction. 
         [0047]    The negative terminal of high voltage battery  112  is directly coupled to system ground. Switch circuit  114  is normally open so that the positive terminal of high voltage battery  112  is disconnected from the positive power input of the high voltage charge circuit  164 . The high voltage charge command HVCHG is also conducted via conductor  149  to the control input of switch circuit  114 , and switch circuit  114  closes in response to connect positive high voltage battery voltage EXT B+ to the positive power input of high voltage charge circuit  164 . Switch circuit  114  may be, for example, a field effect transistor (FET) with its source-to-drain path interrupting the EXT B+ conductor  118  and its gate receiving the HVCHG signal on conductor  145 . High voltage charge circuit  164  is thereby rendered ready to begin charging the high voltage output capacitors  156 ,  158 ,  160 , and  162  with charging current from high voltage battery  112 . 
         [0048]    High voltage output capacitors  156 ,  158 ,  160 , and  162  may be charged to very high voltages, e.g., 300-1000V, to be discharged through the body and heart between the electrode pair of subcutaneous cardioversion-defibrillation electrodes  113  and  123 . The details of the voltage charging circuitry are also not deemed to be critical with regard to practicing the present disclosure; one high voltage charging circuit believed to be suitable for the purposes of the present disclosure is disclosed. High voltage capacitors  156 ,  158 ,  160  and  162  may be charged, for example, by high voltage charge circuit  164  and a high frequency, high-voltage transformer  168  as described in detail in commonly assigned U.S. Pat. No. 4,548,209 “Energy Converter for Implantable Cardioverter” to Wielders, et al. Proper charging polarities are maintained by diodes  170 ,  172 ,  174  and  176  interconnecting the output windings of high-voltage transformer  168  and the capacitors  156 ,  158 ,  160 , and  162 . As noted above, the state of capacitor charge is monitored by circuitry within the high voltage output circuit  140  that provides a VCAP, feedback signal indicative of the voltage to the timing and control circuit  144 . Timing and control circuit  144  terminates the high voltage charge command HVCHG when the VCAP signal matches the programmed capacitor output voltage, i.e., the cardioversion-defibrillation peak shock voltage. 
         [0049]    Control circuit  144  then develops first and second control signals NPULSE  1  and NPULSE  2 , respectively, that are applied to the high voltage output circuit  140  for triggering the delivery of cardioverting or defibrillating shocks. In particular, the NPULSE  1  signal triggers discharge of the first capacitor bank, comprising capacitors  156  and  158 . The NPULSE  2  signal triggers discharge of the first capacitor bank and a second capacitor bank, comprising capacitors  160  and  162 . It is possible to select between a plurality of output pulse regimes simply by modifying the number and time order of assertion of the NPULSE  1  and NPULSE  2  signals. The NPULSE  1  signals and NPULSE  2  signals may be provided sequentially, simultaneously or individually. In this way, control circuitry  144  serves to control operation of the high voltage output stage  140 , which delivers high energy cardioversion-defibrillation shocks between the pair of the cardioversion-defibrillation electrodes  113  and  123  coupled to the HV-1 and COMMON output as shown in  FIG. 3A . 
         [0050]    Thus, subcutaneous device  14  monitors the patient&#39;s cardiac status and initiates the delivery of a cardioversion-defibrillation shock through the cardioversion-defibrillation electrodes  24  and  28  in response to detection of a tachyarrhythmia requiring cardioversion-defibrillation. The high HVCHG signal causes the high voltage battery  112  to be connected through the switch circuit  114  with the high voltage charge circuit  164  and the charging of output capacitors  156 ,  158 ,  160 , and  162  to commence. Charging continues until the programmed charge voltage is reflected by the VCAP signal, at which point control and timing circuit  144  sets the HVCHG signal low terminating charging and opening switch circuit  114 . Typically, the charging cycle takes only fifteen to twenty seconds, and occurs very infrequently. The subcutaneous device  14  can be programmed to attempt to deliver cardioversion shocks to the heart in (the manners described above in timed synchrony with a detected R-wave or can be programmed or fabricated to deliver defibrillation shocks to the heart in the manners described above without attempting to synchronize the delivery to a detected R-wave. Episode data related to the detection of the tachyarrhythmia and delivery of the cardioversion-defibrillation shock can be stored in RAM for uplink telemetry transmission to an external programmer as is well known in the art to facilitate in diagnosis of the patient&#39;s cardiac state. A patient receiving the device  14  on a prophylactic basis would be instructed to report each such episode to the attending physician for further evaluation of the patient&#39;s condition and assessment for the need for implantation of a more sophisticated ICD. 
         [0051]      FIG. 5  is a schematic diagram of a rectifier and auto-threshold unit in a subcutaneous device according to an embodiment of the present disclosure. Waveform  402  depicts a typical subcutaneous ECG waveform and waveform  404  depicts the same waveform after filtering and rectification. A time dependant threshold  406  allows a more sensitive sensing threshold temporally with respect to the previous sensed R-wave. Sensed events  408  indicate when the rectified ECG signal  404  exceeds the auto-adjusting threshold and a sensed event has occurred. 
         [0052]    Turning to  FIG. 3B , the subcutaneous ECG signal (ECG 1 ) is applied to ECG morphology block  232 , filtered by a 2-pole 23 Hz low pass filter  252  and evaluated by DSP microcontroller  254  under control of program instructions stored in System Instruction RAM  258 . ECG morphology is used for subsequent rhythm detection/determination (to be described herein below). 
         [0053]    Subcutaneous device  14  desirably includes telemetry circuit (not shown in  FIG. 3A ), so that it is capable of being programmed by means of external programmer  20  via a 2-way telemetry link  22  (shown in  FIG. 1 ). Uplink telemetry allows device status and diagnostic/event data to be sent to external programmer  20  for review by the patients physician. Downlink telemetry allows the external programmer via physician control to allow the programming of device function and the optimization of the detection and therapy for a specific patient. Programmers and telemetry systems suitable for use in the practice of the present disclosure have been well known for many years. Known programmers typically communicate with an implanted device via a bi-directional radio-frequency telemetry link, so that the programmer can transmit control commands and operational parameter values to be received by the implanted device, so that the implanted device can communicate diagnostic and operational data to the programmer. Programmers believed to be suitable for the purposes of practicing the present disclosure include the Models 9790 and CareLink® programmers, commercially available from Medtronic, Inc., Minneapolis, Minn. 
         [0054]    Various telemetry systems for providing the necessary communications channels between an external programming unit and an implanted device have been developed and are well known in the art. Telemetry systems believed to be suitable for the purposes of practicing the present disclosure are disclosed, for example, in the following U.S. patents: U.S. Pat. No. 5,127,404 to Wyborny et al. entitled “Telemetry Format for Implanted Medical Device”; U.S. Pat. No. 4,374,382 to Markowitz entitled “Marker Channel Telemetry System for a Medical Device”; and U.S. Pat. No. 4,556,063 to Thompson et al. entitled “Telemetry System for a Medical Device”. The Wyborny et al. &#39;404, Markowitz &#39;382, and Thompson et al. &#39;063 patents are commonly assigned to the assignee of the present disclosure, and are each hereby incorporated by reference herein in their respective entireties. 
         [0055]      FIG. 3B  is a schematic diagram of signal processing aspects of a subcutaneous device according to an exemplary embodiment of the present disclosure. The transthoracic ECG signal (ECG 1 ) detected between the distal electrode  26  of subcutaneous lead  18  and one of electrodes  28  positioned on the subcutaneous device  14  are amplified and bandpass filtered (2.5-105 Hz) by pre-amplifiers  202  and  206  located in Sense Amp  190  of  FIG. 3A . The amplified EGM signals are directed to A/D converters  210  and  212 , which operate to sample the time varying analog EGM signal and digitize the sampled points. The digital output of A/D converters  210  and  212  are applied to temporary buffers/control logic, which shifts the digital data through its stages in a FIFO manner under the control of Pacer/Device Timing block  178  of  FIG. 3A . Virtual Vector block  226  selects one housing-based EGG signal (ECG 2 ) from any pair of electrodes  28  as described, for example, in U.S. Pat. No. 5,331,966 “Subcutaneous Multi-Electrode Sensing System, Method and Pacer” to Bennett, et al. or, alternatively, generates a virtual vector signal under control of Microprocessor  142  and Control block  144  as described in U.S. Pat. No. 6,505,067 “System and Method for Deriving Virtual ECG or EGM Signal” to Lee, et al; both patents incorporated herein by reference in their entireties. ECG 1  and ECG 2  vector selection may be selected by the patient&#39;s physician and programmed via telemetry link  22  from programmer  20 . 
         [0056]    According to an embodiment of the present disclosure, in order to automatically select the preferred ECG vector set, it is necessary to have an index of merit upon which to rate the quality of the signal. “Quality” is defined as the signal&#39;s ability to provide accurate heart rate estimation and accurate morphological waveform separation between the patient&#39;s usual sinus rhythm and the patients ventricular tachyarrhythmia. 
         [0057]    Appropriate indices may include R-wave amplitude, R-wave peak amplitude to waveform amplitude between R-waves (i.e., signal to noise ratio), low slope content, relative high versus low frequency power, mean frequency estimation, probability density function, or some combination of these metrics. 
         [0058]    Automatic vector selection can be done at implantation or periodically (daily, weekly, monthly) or both. At implant, automatic vector selection may be initiated as part of an automatic device turn-on procedure that performs such activities as measure lead impedances and battery voltages. The device turn-on procedure may be initiated by the implanting physician (e.g., by pressing a programmer button) or, alternatively, may be initiated automatically upon automatic detection of device/lead implantation. The turn-on procedure may also use the automatic vector selection criteria to determine if ECG vector quality is adequate for the current patient and for the device and lead position, prior to suturing the subcutaneous device  14  device in place and closing the incision. Such an ECG quality indicator would allow the implanting physician to maneuver the device to a new location or orientation to improve the quality of the ECG signals as required. The preferred ECG vector or vectors may also be selected at implant as part of the device turn-on procedure. The preferred vectors might be those vectors with the indices that maximize fate estimation and detection accuracy. There may also be an a priori set of vectors that are preferred by the physician, and as long as those vectors exceed some minimum threshold, or are only slightly worse than some other more desirable vectors, the a priori preferred vectors are chosen. Certain vectors may be considered nearly identical such that they are not tested unless the a priori selected vector index falls below some predetermined threshold. 
         [0059]    Depending upon metric power consumption and power requirements of the device, the ECG signal quality metric may be measured on the range of vectors (or alternatively, a subset) as often as desired. Data may be gathered, for example, on a minute, hourly, daily, weekly or monthly basis. More frequent measurements (e.g., every minute) may be averaged over time and used to select vectors based upon susceptibility of vectors to occasional noise, motion noise, or EMI, for example. 
         [0060]    Alternatively, the subcutaneous device  14  may have an indicator/sensor of patient activity (piezo-resistive, accelerometer, impedance, or the like) and delay automatic vector measurement during periods of moderate or high patient activity to periods of minimal to no activity. One representative scenario may include testing/evaluating ECG vectors once daily or weekly while the patient has been determined to be asleep (using an internal clock (e.g., 2:00 am) or, alternatively, infer sleep by determining the patient&#39;s position (via a 2- or 3-axis accelerometer) and a lack of activity). 
         [0061]    If infrequent automatic, periodic measurements are made, it may also be desirable to measure noise (e.g., muscle, motion, EMI, etc.) in the signal and postpone the vector selection measurement when the noise has subsided. 
         [0062]    Subcutaneous device  14  may optionally have an indicator of the patient&#39;s posture (via a 2- or 3-axis accelerometer). This sensor may be used to ensure that the differences in ECG quality are not simply a result of changing posture/position. The sensor may be used to gather data in a number of postures so that ECG quality may be averaged over these postures or, alternatively, selected for a preferred posture. 
         [0063]    In the preferred embodiment, vector quality metric calculations would occur a number of times over approximately 1 minute, once per day, for each vector. These values would be averaged for each vector over the course of one week. Averaging may consist of a moving average or recursive average depending on time weighting and memory considerations. In this example, the preferred vector(s) would be selected once per week. 
         [0064]    Continuing with  FIG. 3B , a diagnostic channel  228  receives a programmable selected ECG signal from the housing based subcutaneous electrodes and the transthoracic ECG from the distal electrode  26  on lead  18 . Block  238  compresses the digital data, the data is applied to temporary buffers/control logic  218  which shifts the digital data through its stages in a FIFO manner under the control of Pacer/Device Timing block  178  of  FIG. 3A , and the data is then stored in SRAM block  244  via direct memory access block  242 . 
         [0065]    The two selected ECG signals (ECG 1  and ECG 2 ) are additionally used to provide R-wave interval sensing via EGG sensing block  230 . IIR notch filter block  246  provides 50/60 Hz notch filtering. A rectifier and auto-threshold block  248  provides R-wave event detection as described in U.S. Pat. No. 5,117,824 “Apparatus for Monitoring Electrical Physiologic Signals” to Keimel, et al; publication WO2004023995 “Method and Apparatus for Cardiac R-wave Sensing in a Subcutaneous ECG Waveform” to Cao, et al. and U.S. Publication No. 2004/0260350 “Automatic EGM Amplitude Measurements During Tachyarrhythmia Episodes” to Brandstetter, et al, all incorporated herein by reference in their entireties. The rectifier of block  248  performs full wave rectification on the amplified, narrowband signal from bandpass filter  246 . A programmable fixed threshold (percentage of peak value), a moving average or, more preferably, an auto-adjusting threshold is generated as described in the &#39;824 patent or &#39;350 publication. In these references, following a detected depolarization, the amplifier is automatically adjusted so that the effective sensing threshold is set to be equal to a predetermined portion of the amplitude of the sensed depolarization, and the effective sensing threshold decays thereafter to a lower or base-sensing threshold. A comparator in block  248  determines signal crossings from the rectified waveform and auto-adjusting threshold signal. A timer block  250  provides R-wave to R-wave interval timing for subsequent arrhythmia detection (to be described herein below). The heart rate estimation is derived from the last 12 R-R intervals (e.g., by a mean, trimmed mean, or median, for example), with the oldest data value being removed as a hew data value is added. 
         [0066]    Some of the operating modes of the device circuitry of  FIG. 3A  are depicted in the flow charts ( FIGS. 4-6 ) and described as follows. The particular operating mode is a programmed or hard-wired sub-set of the possible operating modes as also described below. For convenience, the algorithm of  FIGS. 4-6  is described in the context of determining the PEI delay and computing the A-LVp intervals to optimally pace the LV chamber to produce electromechanical fusion with the corresponding intrinsic depolarization of the RV chamber. The RV chamber depolarizes intrinsically so that the pre-excited electromechanical fusion occurs as between the intrinsically activated RV chamber and the pre-excitation evoked response of the LV chamber. As noted below, the algorithm can be employed to determine an optimal PEI delay that results in an A-LVp interval producing ventricular synchrony (i.e., CRT delivery via a single ventricular pacing stimulus). Of course, the methods according to the present disclosure are intended to be stored as executable instructions on any appropriate computer readable medium although they may be performed manually as well. 
         [0067]      FIG. 4  illustrates one embodiment of the present disclosure wherein the IPG circuit  300  includes a method  400  beginning with step S 402  that is periodically performed to determine the intrinsic ventricular delay between the LV and the RV. In step  402  the first-to-depolarize ventricle is labeled RV and the second-to-depolarize ventricle is labeled LV and the corresponding shortest A-V interval is stored as the “A-RV” delay interval. In step  404  the A-RV delay interval is decremented by the PEI to generate the A-LVp interval for delivering pacing stimulus to the LV chamber. The magnitude of the PEI depends on several factors, including internal circuitry processing delay, location of sensing electrodes, location of pacing electrodes, heart rate, dynamic physiologic conduction status (e.g., due to ischemia, myocardial infarction, LBBB or RBBB, etc.). However, the inventors have found that a PEI of approximately 20-40 milliseconds (ms) oftentimes provides adequate pre-excitation to the LV chamber resulting in electromechanical fusion of both ventricles. However, a reasonable range for the PEI runs from about one ms to about 100 ms (or more). Of course, an iterative subroutine for decrementing the A-RV delay can be used and/or a clinical procedure utilized to help narrow a range of prospective values for the magnitude of the decrease in the A-RV delay. According to this part of the present disclosure a series of decrements are implemented over a series of at least several cardiac cycles (as needed for the hemodynamic or contractile response to stabilize). 
         [0068]    In another aspect, a data set is generated for a range of heart rates that correspond to measured A-RV (and/or A-LV) delay intervals. The data may include paced or intrinsic heart rate data (ppm and bpm, respectively). In this aspect of the disclosure, the data set can be employed as a guiding or a controlling factor during heart rate excursions for continuous delivery of the single ventricular pre-excitation pacing of the present disclosure. In one form of this aspect of the disclosure, internal physiologic sensor data may be used as a guiding factor when determining an appropriate setting for the PEI (A-LV). 
         [0069]    In yet another aspect, a first data set of appropriate values of the A-LV delay interval are based on evoked response (i.e., wherein the A-EVENT is a pacing event) and a second data set of appropriate values of the A-LV delay interval are based on intrinsic response (i.e., wherein the A-EVENT is a natural atrial depolarization). 
         [0070]    Following the decrementing step  404  the A-LVp (pacing) delay interval is set and in step  406  pre-excitation pacing therapy is delivered to the LV chamber upon expiration of the A-RVp interval. 
         [0071]    In the presently illustrated embodiment of the disclosure, pre-excitation pacing therapy delivery continues until: a pre-set number of cardiac cycles occur, a preset time period expires, a loss of capture occurs in the LV chamber, or a physiologic response trigger event occurs. The physiologic response trigger will be described below. With respect to the other three situations, the number of cardiac cycles or the time period may be set to any clinically appropriate value, given the patient&#39;s physiologic condition (among other factors) before returning to step  402  and (redetermining the physiologic A-RV interval and deriving an operating PEI (A-LVp). If a loss of capture in the LV chamber is detected it could indicate that the LVp (pacing) stimulus is being delivered too late (e.g., during the refractory period of the LV chamber) or that the LV pacing electrodes have malfunctioned or become dislodged. While the process  400  depicted in  FIG. 4  reflect that under all the foregoing situations steps  402 - 406  should be performed following events (i)-(iii), the pre-excitation pacing therapy could of course be terminated. 
         [0072]    With respect to the physiologic response trigger event(s)—as well as optionally with respect to condition (iii) wherein loss of capture of the LV chamber occurs due to inappropriate timing of the LV pacing stimulus—at step  410  an iterative closed-loop process for determining an appropriate A-LVp interval is performed. In step  410 , the A-LVp interval is directly manipulated from a prior operating value while one or more physiologic response, is monitored and/or measured and stored. As mentioned above with respect to step  404  with regard to decrementing the intrinsic A-RV interval to generate the operating A-LVp interval, a number of sensors may be employed. After storing the physiologic response data (and corresponding PEI used during data collection) at step  412  the data is compared and the PEI corresponding to the most favorable physiologic response is then programmed as the operating PEI. The process then proceeds back to step  406  and the LV chamber receives pre-excitation pacing therapy upon the expiration of the physiologically-derived PEI. Of course, of the foregoing steps, steps  402 , 404 , 406  may be performed wherein step  402  (deriving the PEI from A-RV interval) is only performed occasionally (e.g., every ten cardiac cycles, during heart rate excursions, etc.). In this form of the disclosure, the magnitude of the decrement of the A-RV, or the PEI itself, can be based upon one or more prior operating PEI value (and several prior operating PEI values, with the most recent PEI receiving additional statistical weighting). In addition to or in lieu of the foregoing a look up table (LUT) or other data compilation, as described above, may be utilized to guide or control the derivation of the PEI value (as described in more detail with respect to  FIG. 5 ). 
         [0073]    Now turning to  FIG. 5 , another embodiment of a method according to the present disclosure is depicted as process  500 . To begin process  500 , the steps  502 ,  504 ,  506 ,  508  correspond closely to the corresponding steps of process  400  ( FIG. 4 ) just described. However, at step  510 —in the event that condition (iv) of step  508  is declared—a data set (or LUT) of physiologic responses and corresponding PEI values for a given patient is accessed. At step  512  the PEI is programmed to a value corresponding to the current physiologic response trigger for the patient. Then, at step  506 , pre-excitation pacing ensues upon expiration of the newly programmed PEI. A representative physiologic response trigger includes an upward or downward heart rate excursion, a sensed lack of ventricular synchrony (based on accelerometer, pressure, EGM or other physiologic data signals) and the like. 
         [0074]    In  FIG. 6 , a process  600  for periodically ceasing delivery of the pre-excitation, single ventricular pacing therapy to perform a pacing mode switch to a different form of pre-excitation therapy, ceasing pre-excitation therapy, or allowing normal sinus rhythm to continue (chronically) is illustrated. The process  600  can be implemented as a part of steps  402 ,  502  (of process  400  and  500 , respectively) for determining the intrinsic A-RV interval or can be performed independently. In either case, process  600  is designed to help reveal improvement (or decline) of a patient&#39;s condition. In the former case, if so-called “reverse remodeling” of the myocardium occurs resulting in return of ventricular synchrony and improved hemodynamics and autonomic tone, pre-excitation therapy delivery may be temporarily or permanently terminated. The patient may, in the best scenario, be relieved of pacing therapy delivery altogether (programming the pacing circuitry to an ODO monitoring-only “pacing modality”). Assuming the patient is not chronotropically incompetent, normal sinus rhythm may emerge permanently for all the activities of daily living. Additionally, the process  600  may be employed to search for a change in conduction status (e.g., wherein LV changes from LV to RV, or wherein A-RV conduction timing changes, etc.). According to process  600 , at step  602  the delivery of pre-excitation therapy ceases and for at least one cardiac cycle the intrinsic, normal sinus rhythm is allowed to emerge. At step  604  the depolarization(s) of the LV and RV are monitored (and, optionally stored in memory). At step  606  a comparison of the depolarization timing is compared and at decision step  608  three outcomes are determined based on the comparison of depolarization timing. If the RV depolarization occurs prior to the LV depolarization then step  610  is performed wherein the LV comprises the LV chamber and A-LVp pre-excitation is initiated (according to process  400  or  500  or analogues thereof). However, if the LV depolarization occurs prior to the RV depolarization then step  612  is performed wherein the RV comprises the LV chamber and A-RVp pre-excitation is initiated (according to process  400  or  500  or analogues thereof). Finally, if the RV depolarization occurs substantially at the same time as the LV depolarization then step  614  is performed. In step  614 , either normal sinus rhythm is allowed to continue or a non-pre-excitation pacing therapy is initiated. 
         [0075]    In addition to or in lieu of the subject matter described above, fusion pacing can be suspended for one or more cardiac cycles while RV depolarization(s) are monitored. Also, a form of CRT delivery could be implemented wherein the LV pacing therapy delivery is triggered off a sensed (intrinsic) depolarization of the RV chamber. The latter technique allows collection of intrinsic A-RV timing while still preserving some of the hemodynamic benefit of CRT delivery. 
         [0076]    It should be understood that certain of the above described structures, functions and operations of the pacing systems of the illustrated embodiments are not necessary to practice the present disclosure and are included in the description simply for completeness of an exemplary embodiment or embodiments. It will also be understood that there may be other structures, functions and operations ancillary to the typical operation of an implantable pulse generator that are not disclosed and are not necessary to the practice of the present disclosure.