Abstract:
Accordingly, according to the present invention a programmable IMD provides a patient with an essentially customized cardiac pacing therapy resulting in enhanced hemodynamic function. In particular, the present invention provides for refined tuning of pacing parameters to cause the heart to pump blood and perfuse in an efficient manner. In general, the invention promotes good hemodynamic operation through programming of an implantable medical device (IMD) as a function of one or more hemodynamic data sensed by a device located external to the body of the patient relying on said data as gathered either by discrete internal measuring device or an external device. The ability to share data among and between an IMD, an IMD programming device and a hemodynamic monitoring or measuring device spaced from the IMD (i.e., either an implantable device or external to the patient) allows for improved selection of pacing parameters to optimize hemodynamic function.

Description:
CROSS REFERENCE TO RELATED APPLICATIONS  
         [0001]    This patent disclosure hereby incorporates by reference the following patent applications filed on even date hereof; namely, P-11214, “Method and Apparatus for Detecting Myocardial Electrical Recovery and Controlling Extra-Systolic Stimulation; P-11216, “Method and Apparatus to Monitor Pulmonary Edema; P-11252, “Method and Apparatus for Determining Myocardial Electrical Resitution and Controlling Extra Systolic Stimulation; and P-11215, “Use of Activation and Recovery Times and Dispersions to Monitor Heart Failure Status and Arrhythmia Risk”.  
         TECHNICAL FIELD  
         [0002]    The invention relates to cardiac pacing systems, and more particularly to programmable cardiac pacing systems and automatic optimization of pacing parameters by iteratively altering one or more such pacing parameters and capturing at least one hemodynamic response resulting therefrom with an external and/or an internal sensing or measuring device.  
         BACKGROUND  
         [0003]    Many patients receive an implantable medical device (IMD), such as a pacemaker, an implantable cardioverter-defibrillator, and the like that addresses abnormal cardiac rates or rhythms. One common type of IMD is a pacemaker that senses cardiac activity such as single or multiple chamber depolarization (i.e., left or right atrial and/or ventricular activity) and delivers timed electrical stimulation therapy to activate one or more atria or ventricles. Typically, one or more deployable medical electrical leads (or other electrodes) coupled to such an IMD senses an atrial activation or causes an atrial activation with an electrical pacing stimulus and after a predetermined time interval provides pacing stimulus to one or both ventricles.  
           [0004]    Some patients, such as those suffering from heart failure, develop a wide QRS complex resulting from a delayed activation of one of the ventricles in the heart, and inter- and/or intra-ventricular electrical-mechanical dysynchrony. Such dysynchrony may worsen heart failure symptoms. For example, the patient may experience a reduction in cardiac output because the ventricles begin or complete contracting at significantly different times. The timing imbalance may also cause the patient to experience paraoxysmal septal motion, mitral regurgitation and/or inadequate atrial contribution to ventricular filling, and the like.  
           [0005]    Patients having a wide QRS complex or having inter- and/or intra-ventricular electrical-mechanical dysynchrony appear to benefit from therapy provided by synchronized pacing therapy provided to both ventricles. This particular tyupe of pacing therapy has become known as cardiac resynchronization therapy (CRT). In one generic form of CRT electrodes operably coupled to IMD circuitry sense (or pace) atrial chamber activity, and then after a predetermined time interval after each sensed or paced atrial activation, provide synchronized bi-ventricular pacing therapy. Accordingly, each ventricular chamber may be paced simultaneously, or one ventricle may be paced before another. When one ventricle is paced before the other, the time delay between ventricular paces is generally known as a V-V interval. This bi-ventricular pacing is one form of cardiac resynchronization, and it presently improves the quality of life, exercise capacity and overall cardiac function for many heart failure patients. Cardiac resynchronization therapy may also be applied to the atria. The atria may be paced simultaneously, or one atrium may be paced before the other. When one atrium is paced before the other, the time delay between atrial paces is generally known as an A-A interval. These intervals, among others, represent pacing parameters and adjustment of one of more of such intervals can have disparate effects on hemodynamic function.  
           [0006]    Due in part to the importance of improving hemodynamic function, particularly for heart failure patients, the present invention provides a method and apparatus for applying select pacing parameters and pacing parameter combination to enhance hemodynamic function.  
         SUMMARY  
         [0007]    Accordingly, according to the present invention a programmable IMD provides a patient with an essentially customized cardiac pacing therapy resulting in enhanced hemodynamic function. In particular, the present invention provides for refined tuning of pacing parameters to cause the heart to pump blood and perfuse in an efficient manner. In general, the invention promotes good hemodynamic operation through programming of an implantable medical device (IMD) as a function of one or more hemodynamic data sensed by a device located external to the body of the patient relying on said data as gathered either by discrete internal measuring device or an external device. The ability to share data among and between an IMD, an IMD programming device and a hemodynamic monitoring or measurement device spaced from the IMD (i.e., either an device implanted within or external to the body of a patient) allows for improved selection of pacing parameters to optimize hemodynamic function.  
           [0008]    In a typical application, a programmer sets a pacing parameter in the IMD. An external device monitors the patient while the IMD applies the pacing parameter, and generates hemodynamic data indicative of hemodynamic function. By example and without limitation, representative hemodynamic data include (or can be derived from) stroke volume, cardiac output, heart rate, ECG/EGM, heart sounds, blood pressure, blood flow, temperature, tissue impedance, trans-thoracic impedance, body fluid analysis (e.g., saturated oxygen, carbon dioxide, pH, lactate), tissue saturation (e.g., relating to pulmonary edema and the like), circulation delay time (e.g., a time period from an initial stimulation or perturbation of the cardiovascular system to detection of a corresponding response), cardiac tissue contractility index, mechanical restitution (MR), recirculation fraction (RF), ejection fraction, acceleration or movement of various parts of the heart (e.g., portions of atrial or ventricular wall tissue, septal wall tissue, and the like), volumetric (or dimension) data for a heart during the cardiac cycle, and various dedicated left- and right-side hemodynamic measurements as is known in the art, but as used herein, hemodynamic data encompasses any metric that reflects or relates to actual hemodynamic function. In addition, first and second derivatives and integrals of the foregoing may be used to derive or integrate primary measurements, respectively, to produce additional hemodynamic data useful when practicing the present invention.  
           [0009]    Furthermore, in the context of the present patent disclosure, the rubric of “hemodynamic data” includes without limitation data reflecting cardiac mechanical function. For example, contractility metrics as measured by diverse sensors such as accelerometer(s) adapted to be coupled to endo-, epi- or peri-cardial tissue, blood pressure sensors, fluid flow sensors, and the like may be used to adjust pacing parameters according to the present invention. Dispersion of depolarization wave fronts (and corresponding wave backs) through and around features of a patient&#39;s cardiac physiology as measured by pacing, defibrillation electrodes and/or other electrodes disposed around or near the heart.  
           [0010]    Accordingly, at least one piece of said hemodynamic data is utilized when practicing the present invention; however, in one embodiment of the invention a plurality of such data is used to select pacing parameters to optimize hemodynamic function. Also, collection of such data may occur over a very short period of time and/or may represent longer-term trend information although such data collection typically lags any changes to one or more pacing parameters by at least a few minutes so that any transient effects are minimized.  
           [0011]    From time to time in the present patent disclosure intrinsic cardiac events are distinguished from evoked cardiac events. Thus, the phrase “pacing parameter” is meant to comprehend myriad pacing parameters, including timed, device-related cardiac pacing intervals (e.g., A-A, V-V, A-V, V-A, etc.) and intrinsic intervals (e.g., P-P, P-R, R-R, R-P, etc.) and combinations thereof (e.g., A-R, P-V, R-A, V-A, etc.) and the like. The phrase “pacing parameters” is also intended to include intrinsic heart rate information (typically expressed as beats-per-minute or bpm) as well as paced heart rate (expressed as paces-per-minute or ppm) and intervals related thereto. For example, programmed sensing intervals (e.g., SAV or “sensed A-V” interval, PAV or “paced A-V” interval, and the like), and blanking periods (e.g., PVAB or “post-ventricular atrial blanking”) and programmable refractory periods (e.g., PVARP or “post-ventricular atrial refractory period”) and the like. Further, in this disclosure pacing stimulus information such as stimulus amplitude, duration, and waveform type (e.g., mono-, bi- or multi-phasic, etc.) and/or rate and the like are also included under the rubric of “pacing parameters.” In addition, the phrase is intended to include the so-called pacing modality or schema (e.g., DDD, VVI, ADI, AAI, VOO, etc.) as well as rate-responsive derivatives thereof. As mentioned previously, the phrase is also intended to cover pacing modalities such as CRT (or bi-ventricular therapy) as well as the relatively new pacing modality becoming known as minimum ventricular pacing (MVP) therapy. One form of MVP therapy involves periodically confirming intact AV conduction and delivering atrial-biased pacing therapy (e.g., AAI/R or ADI/R) and changing to dual chamber or ventricular pacing therapy if AV conduction is lacking (e.g., DDD/R, DDI/R, VVI, etc.). Moreover, the phrase pacing parameters includes newly re-emerging pacing modalities and related parameters such as those related to paired or coupled pacing therapy (also known as post extra-systolic potentiation therapy or PESP therapy) which include the notion of an extra-systolic interval (ESI) for the time period between a ventricular pace or an intrinsic ventricular depolarization and an electrical augmentation stimulus delivered shortly after the relative refractory period of said ventricle. The PESP therapy may include additional parameters a cardiac stress index (CSI), a cardiac performance index (CPI) and diverse other pacing parameters. With respect to PESP, the following references are incorporated by reference herein, U.S. Pat. No. 6,213,098 to Bennett et al. and assigned to Medtronic, Inc. and non-provisional U.S. patent application Ser. No. 10/232,792 (Atty. Dkt. P-9854.00) filed 28 Aug. 2002. The phrase pacing parameters can without limitation also include anti-arrhythmia therapy parameters such as anti-tachycardia pacing (ATP), electrical stimulation metrics for atrial or ventricular cardioversion and/or defibrillation (e.g., a pacing threshold, a defibrillation threshold, a cardioversion threshold). Finally, the phrase pacing parameters without limitation includes timing of intrinsic arrhythmic events such as one or more premature atrial or ventricular contraction (PAC or PVC, respectively), ventricular tachycardia (VT), ventricular fibrillation (VF), atrial fibrillation (AF), and the like.  
           [0012]    In practicing the present invention, an IMD programming device receives at least one piece of hemodynamic data from one or more hemodynamic measurement device (one or more external and/or co-implantable devices), and programs one or more pacing parameters of the IMD as a function of one or more pieces of the hemodynamic data. The IMD programming device, of course, is also telemetrically linked to the IMD and may read, write or store virtually any pacing parameter of the IMD to the IMD and/or to the IMD programming device. The hemodynamic measurement device continues to monitor the patient and generates an updated piece of hemodynamic data, and the programmer may set the one or more pacing parameters again as a function of the updated hemodynamic date.  
           [0013]    In addition, the IMD may communicate physiologic data and/or pacing parameter settings to the hemodynamic measuring device(s). Thus, the duty cycle or timing for any measurements can be efficiently enhanced for example, by triggering data collection to a predetermined time interval when the measurement is most readily or efficiently taken. In the event that one or more of the measuring device(s) are also implanted such efficiency results in conservation of the power source for such device(s) while limiting the amount of filtering required to produce usable hemodynamic data, among other advantages.  
           [0014]    In this way, an IMD programming device may iteratively program one or more pacing parameters of an IMD. When the hemodynamic measurement device generates a hemodynamic datum indicating that the hemodynamic operation of the patient appears optimized (or at least satisfactory), the IMD programming device establishes said one or more pacing parameters by programming the IMD accordingly.  
           [0015]    In one embodiment, the invention is directed to a method comprising receiving at least one hemodynamic data from a hemodynamic measuring device (e.g., a device external to or implanted within the body of a patient) and setting a pacing parameter in an IMD as a function of the hemodynamic data. In another embodiment, the invention is directed to a method comprising setting a pacing parameter in an implantable medical device to a first setting and receiving hemodynamic data from a hemodynamic measuring device while the pacing parameter is at the first setting. In further embodiments, the invention is directed to a computer-readable medium containing instructions that cause a programmable processor to carry out any of the foregoing methods.  
           [0016]    In an additional embodiment, the invention is directed to processor-based devices. The processor receives a hemodynamic data item from a device implanted in the body of a patient or from an external device, or both, and generates a pacing parameter setting for the implanted device as a function of the hemodynamic data.  
           [0017]    In another embodiment, the invention provides a hemodynamic measurement device that is wholly external to the body of a patient. The device comprising a sensor to measure a hemodynamic datum from a body of a patient and a transmitter to transmit the hemodynamic datum to an IMD programmer. As mentioned previously, the operation of the hemodynamic measurement device is optionally enhanced by receiving information, including pacing parameter information, from an IMD so that the hemodynamic measurement device more efficiently and/or accurately measures hemodynamic function of the patient.  
           [0018]    In an added embodiment, the invention is directed to a system that includes a sensing device, a programmer, and an implantable medical device. The sensing device is external to the body of the patient and measures a hemodynamic datum. The programmer, which may be external or implanted, generates a pacing parameter setting as a function of the hemodynamic datum. The implantable medical device applies pacing stimuli to a heart according to the pacing parameter setting.  
           [0019]    The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent to those of skill in the art to which the present invention is directed upon review of the written description, drawings, and claims appended hereto. 
       
    
    
     BRIEF DESCRIPTION OF DRAWINGS  
       [0020]    [0020]FIG. 1 is a block diagram illustrating an exemplary system that may practice the invention, including an external device, a programmer and an IMD.  
         [0021]    [0021]FIG. 2 illustrates an exemplary IMD that may be programmed using the techniques of the invention, located in and near a heart.  
         [0022]    [0022]FIG. 3 is a functional schematic diagram of the embodiment of the IMD shown in FIG. 2.  
         [0023]    [0023]FIG. 4 is a schematic diagram illustrating an external device for measuring an exemplary hemodynamic datum, transthoracic impedance.  
         [0024]    [0024]FIG. 5A is a timing diagram illustrating an exemplary relation between an exemplary hemodynamic datum, cardiac output, and an exemplary pacing parameter, a V-V interval.  
         [0025]    [0025]FIG. 5B is a timing diagram illustrating a change in the exemplary hemodynamic datum resulting from a change to the exemplary pacing parameter shown in FIG. 5A.  
         [0026]    [0026]FIG. 6 is a flow diagram illustrating an exemplary technique for monitoring a hemodynamic datum and programming an IMD according to an embodiment of the invention. 
     
    
     DETAILED DESCRIPTION  
       [0027]    [0027]FIG. 1 is a block diagram illustrating an example embodiment of a system  10  including an external device  14 , a programmer  16  and an implantable medical device (IMD)  18 . System  10  is shown in FIG. 1 with a patient  20 . In one form of the present invention the external device  14  is external to the body of patient  20 , and in another form of the invention the device  14  may comprise a fully- or partially-implantable device. In both forms of the present invention, the device  14  includes a sensor  24  that senses or measures hemodynamic function of the heart of patient  20 . More particularly, the device  14  generates at least one hemodynamic datum relating to the hemodynamic function, and transmits a signal reflecting the hemodynamic datum via a transmitter unit (TX unit)  22  to programmer  16 . The TX unit  22  may comprise circuitry to establish a wireless or hard-wired communication link with programmer  16 . In addition, mutual communication among the device  14  (whether disposed outside, partially outside or implanted within the patient), the programmer  16  and the IMD  18  is preferably established intermittently or continuously. According to the present invention, such mutual communication enhances the process of optimizing the programming of the IMD  18  and the resulting hemodynamic function of the patient. Furthermore, such mutual communication enhances the operation of device  14 , as more fully described herein.  
         [0028]    The phrase “hemodynamic data” covers any information that relates to one or more discrete characteristics or metrics of the hemodynamic and/or mechanical function of the heart. Typical hemodynamic data include stroke volume, cardiac output and heart rate, as well as any of the factors enumerated above in the Summary of the invention that vary as a reflect directly or indirect on hemodynamic and/or mechanical function of a patient. The present invention is intended to encompass all factors that vary as a function of hemodynamic operation and/or mechanical function of a patient.  
         [0029]    The device  14  comprises any external and/or co-implanted sensor that generates a signal in response to hemodynamic operation or mechanical cardiac function. The device  14  may comprise, for example, an impedance monitor that that measures transthoracic impedance. As will be described in more detail below, transthoracic impedance varies as a function of cardiac output. Device  14  may generate a hemodynamic datum based on one or more transthoracic impedance measurements, thereby providing a measurement of stroke volume.  
         [0030]    Of course, the device  14  is not limited to a transthoracic impedance monitor, and may comprise one or more other sensors that generate one or more signals in response to hemodynamic operation. Furthermore, for convenience the device  14  will primarily be referred to as an “external device” although as previously mentioned the present invention is not to be construed as limited only to non-implanted devices. The device  14  may comprise, for example, a heart rate sensor, a heart sounds sensor, a blood pressure sensor, a blood flow sensor, and other apparatus as more fully set forth in the Summary, and the like. Heart rate, heart sounds, blood pressure and blood flow directly and/or indirectly reflect hemodynamic operation or mechanical function. Furthermore, the device  14  is not limited to a single sensor, but may include any combination of sensors that generate signals in response to hemodynamic operation. The device  14  preferably includes circuitry to telemeter data to and from the programmer  16  and the IMD  18 , including timing circuitry so that the device  14  can make relatively synchronized hemodynamic and other measurements. Also, for some types of telemetry it is possible that interference arising from a device  14  (e.g., an impedance monitor) thereby corrupting telemetry operation. In the event that such interference occurs, appropriate timing or multiplexing techniques and the like may be used to reduce or eliminate such interference.  
         [0031]    Programmer  16  receives the hemodynamic datum from external device  14  via a receiver/transmitter unit (RX/TX unit)  26 . A processor  28  in programmer  16  sets one or more pacing parameters as a function of one or more hemodynamic or mechanical data. In general, the phrase pacing parameter is meant to cover all parameters that govern delivery of electrical stimulation therapy to one or more chambers of the heart of a patient  20 . Pacing parameters may govern, for example, the rate or timing of pacing stimuli. Exemplary pacing parameters include one or more pacing intervals, such as an A-V interval, a V-V interval, and an A-A interval.  
         [0032]    Programmer  16  programs IMD  18  with the pacing parameter. In particular, programmer  16  transmits the pacing parameter setting to IMD  18  via RX/TX unit  26 , and IMD  18  receives the pacing parameter setting via a receiver unit (RX unit)  30 . Typically, RX/TX unit  26  in programmer  16  comprises circuitry to establish a wireless communication link with RX unit  30 .  
         [0033]    IMD  18  further includes a processor  32  that implements the pacing parameter setting. In other words, the pacing parameter setting is an instruction from programmer  16  to IMD  18  that directs the pacing of IMD  18 . IMD  18  implements the pacing parameter setting by applying pacing stimuli to the heart of patient  20 , according to the pacing parameter setting. When the pacing parameter setting specifies a time duration for an A-V interval, for example, IMD  18  paces the heart of patient  20  with the specified A-V interval.  
         [0034]    IMD  18  may comprise a multi-chamber pacemaker and may include cardioversion and defibrillation capabilities. Although an exemplary IMD  18  will be described below in connection with FIG. 2, the invention is not limited to the particular IMD shown.  
         [0035]    When IMD  18  paces the heart of patient according to the pacing parameter setting, the pacing therapy may affect the hemodynamic operation and/or mechanical function of the heart of patient  20  in a measurable way. For example, is the hemodynamic operation of the heart may be improved, or may be made worse, or may stay substantially the same. Sensor  24  in external device  14  senses the hemodynamic operation, and generates a hemodynamic datum that reflects the hemodynamic operation.  
         [0036]    The device  14  communicates the hemodynamic datum to programmer  16 , which may set a new pacing parameter as a function of the hemodynamic datum. Programmer  16  programs IMD  18  with the new pacing parameter setting, and IMD  18  implements the programmed pacing parameter setting. External device  14  monitors the hemodynamic operation that results when IMD  18  paces the heart according to the new pacing parameter setting.  
         [0037]    In this way, system  10  operates as a closed-loop system, monitoring hemodynamic operation and setting pacing parameters as a function of the hemodynamic operation. Processor  28  in programmer  16  determines which pacing parameters produce desirable hemodynamic results, and may terminate programming when the pacing parameters produce those results.  
         [0038]    Although from time to time herein external device  14  is described as external to the body of patient  20  and IMD  18  is implanted in the body of patient  20 , the device  14  may be either external or internal (e.g., co-implanted). Moreover, device  14  may share physical components with programmer  16  or IMD  18 . In FIG. 1, grouping  12 A illustrates an embodiment of the invention in which external device  14  and programmer  16  are both external to the body of patient  20  and share a single housing. In some variations of this embodiment, TX unit  22  may include circuitry to establish a communication link with programmer  16 , or TX unit  22  may be omitted as unnecessary.  
         [0039]    Grouping  12 B illustrates an embodiment in which programmer  16  is implanted in the body of patient  20 , and shares the same housing as IMD  18 . In some variations of this embodiment, the functionality of TX/RX unit  28  and RX unit  30  may be combined into a single communication unit. Processor  28  in programmer  16  and processor  32  in IMD  18  may also be combined into a single processing unit.  
         [0040]    [0040]FIG. 2 illustrates one embodiment of IMD  18  that may apply the techniques of the invention. IMD  18  is depicted in conjunction with a human heart  42 . IMD  18  is multi-chamber implantable cardioverter-defibrillator (ICD), but the invention is not limited to the particular device depicted in FIG. 2. For example, the IMD  18  may be a single chamber device, may have endocardial, epicardial, transvenous and/or subcutaneous medical electrical leads coupled thereto as well as one or more electrodes surface mounted into a part of a canister or housing for operative circuitry, as is known in the art.  
         [0041]    For illustration, a right ventricular lead includes an elongated insulative lead body  48  carrying one or more concentric coiled conductors separated from one another by tubular insulative sheaths. Located adjacent the distal end of lead body  48  are pace/sense electrodes  50 ,  52 . Lead body  48  also includes an elongated coil electrode  56  to apply cardioversion or defibrillation therapy. Each of the electrodes is coupled to one of the coiled conductors within lead body  48 . Electrodes  50  and  52  are employed for cardiac pacing and for sensing depolarizations of right ventricle  38 . At the proximal end of lead body  48  is a connector  58 , which couples the coiled conductors in lead body  48  to a connector module  36 .  
         [0042]    A right atrial lead includes an elongated insulative lead body  78  carrying one or more concentric coiled conductors separated from one another by tubular insulative sheaths corresponding to the structure of ventricular lead body  48 . Located adjacent the J-shaped distal end of lead body  78  are pace/sense electrodes  62 ,  64 , which sense depolarizations of and deliver pacing stimulations to right atrium  40 . Elongated coil electrode  72  is provided proximate to the distal end of lead atrial body  78 , and is located in right atrium  40  and the superior vena cava  70 . At the proximal end of the lead is a connector  68 , which couples the coiled conductors in lead body  78  to connector module  36 .  
         [0043]    A coronary sinus lead shown in FIG. 2 includes an elongated insulative lead body  88  deployed in the great vein  84 . Lead body  88  carries one or more coiled conductors coupled to electrodes  74 , 76 , 94 , 98 . Electrodes  74 , 76  are employed for ventricular pacing and for sensing depolarizations of left ventricle  44 , and electrodes  94 , 98  are employed for atrial pacing and for sensing depolarizations of left atrium  46 . At the proximal end of the coronary sinus lead is connector  86 , which couples the coiled conductors in lead body  88  to connector module  36 .  
         [0044]    The outward facing portion of housing  34  of IMD  18  may include insulation, such as a coating of parylene or silicone rubber. The outward facing portion of housing  34  may, however, be left uninsulated or some other division between insulated and uninsulated portions may be employed. The uninsulated portion of housing  34  serves as a subcutaneous electrode and a return current path for electrical stimulations applied via other electrodes.  
         [0045]    IMD  18  includes an implantable pulse generator (IPG) (not shown in FIG. 2) to generate pacing stimuli, which are delivered to one or more chambers of heart  42 . IMD  18  further includes one or more processors (not shown in FIG. 2) that regulate the delivery of pacing pulses. The processors deliver the pacing stimuli according to one or more pacing parameters based on paced/sensed and intrinsic cardiac activity. The pacing parameters govern, for example, the rate or timing of pacing stimuli, and may include one or more pacing intervals as more fully set forth in the Summary portion of this disclosure.  
         [0046]    IMD  18  is configured to apply a variety of pacing modes, which includes applying a variety of pacing intervals. IMD  18  may sense or pace one or both atria, and may pace one or more ventricles following an A-V interval. When IMD  18  paces both atria, the atrial paces may be separated by an A-A interval, and when IMD  18  paces both ventricles, the ventricular pacing therapy may be separated by a V-V interval. In accordance with the invention, a programmer may program any of the pacing parameters to a particular setting, and IMD  18  paces the heart according to the pacing parameter settings.  
         [0047]    Pacing according to different pacing parameter settings usually affects the hemodynamic operation of heart  42 . A sensor  24  in external device  14  monitors the hemodynamic operation, and generates at least one piece of hemodynamic data that directly or indirectly reflects hemodynamic operation and/or mechanical function of a patient  20 . External device  14  communicates the hemodynamic datum to programmer  16 , which may set a new pacing parameter as a function of the hemodynamic datum and may program IMD  18  with the new pacing parameter setting. As a result of monitoring of the hemodynamic operation of heart  42  by external device  14 , IMD  18  may be programmed with one or more pacing parameter settings that result in satisfactory hemodynamic operation. As mentioned, operation of device  14  can be enhanced by receiving information from the IMD  18 , and/or the programmer  16 , such that the device  14  more readily and efficiently renders measurements related to hemodynamic function.  
         [0048]    The invention is not limited to practice with the particular device shown in FIG. 2. For example, a pacemaker that includes a single atrial lead and a single ventricular lead may apply the techniques of the invention to discover an A-V interval that produces good hemodynamic operation. Similarly, a bi-ventricular pacemaker may apply the techniques of the invention to discover a V-V interval that produces good hemodynamic operation. Also, a cardiac stimulation device that provides PESP therapy and/or electrical stimulation therapy to one or more autonomic nerves also benefits from the teaching of the present invention.  
         [0049]    [0049]FIG. 3 is a functional schematic diagram of one embodiment of IMD  18 . Like FIG. 2, FIG. 3 is exemplary of the type of device that may practice the invention, and the invention is not limited to the particular implementation shown in FIG. 3. On the contrary, the invention may be practiced in a wide variety of device implementations, including devices that lack cardioversion and defibrillation capabilities, and including devices not programmed to address tachyarrhythmias.  
         [0050]    As depicted in FIG. 3, IMD  18  includes a telemetry system  100  for wireless communication with a device such as programmer  16 . IMD  18  further includes an electrode system described above in connection with FIG. 2. Electrode  102  in FIG. 3 includes the uninsulated portion of the housing  34  of IMD  18 . Electrodes  56 ,  72  and  102  are coupled to high voltage output circuit  104 , which includes high voltage switches controlled by cardioversion/defibrillation (CV/defib) control logic  108  via control bus  106 . Switches disposed within output circuit  104  determine which electrodes are employed and which electrodes are coupled to the positive and negative terminals of a capacitor bank (which includes capacitors  110 ) during delivery of defibrillation or cardioversion pulses.  
         [0051]    Electrodes  50 , 52  are located on or in the right ventricle  38  of patient  20  and are coupled to the R-wave amplifier  112 , which may take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured R-wave amplitude. A signal is generated on R-out line  114  whenever the signal sensed between electrodes  50 , 52  exceeds the sensing threshold.  
         [0052]    Similarly, electrodes  94 , 98  are located proximate to left ventricle  44  and are coupled to the R-wave amplifier  116 , which may also take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured R-wave amplitude. A signal is generated on R-out line  118  whenever the signal sensed between electrodes  94  and  98  exceeds the sensing threshold.  
         [0053]    Electrodes  62 , 64  are located proximate to right atrium  40  and are coupled to the P-wave amplifier  120 , which may also take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured P-wave amplitude. A signal is generated on P-out line  122  whenever the signal sensed between electrodes  62 , 64  exceeds the sensing threshold.  
         [0054]    Similarly, electrodes  74 , 76  are located proximate to left atrium  46  and are coupled to the P-wave amplifier  124 , which may also take the form of an automatic gain controlled amplifier providing an adjustable sensing threshold as a function of the measured P-wave amplitude. A signal is generated on P-out line  126  whenever the signal sensed between electrodes  74 , 76  exceeds the sensing threshold.  
         [0055]    Switch matrix  128  is used to select which of the available electrodes are coupled to amplifier  130  for use in digital signal analysis. Selection of electrodes is controlled by microprocessor  132  via data/address bus  134 . Signals from the electrodes selected for coupling to amplifier  130  are provided to multiplexer  136 , and thereafter converted to multi-bit digital signals by analog-to-digital (A/D) converter  138 , for storage in random access memory (RAM)  140  under control of direct memory access (DMA) circuit  142 . Microprocessor  132  may employ digital signal analysis techniques to characterize the digitized signals stored in RAM  140  to recognize and classify the patient&#39;s heart rhythm employing any signal processing methodology.  
         [0056]    Pacer timing/control circuitry  144  includes programmable digital counters which control the basic time intervals associated with various modes of single- and multi-chamber pacing. Pacer timing/control circuitry  144  also controls escape intervals associated with anti-tachyarrhythmia pacing in both the atrium and the ventricle, employing anti-tachyarrhythmia pacing therapies.  
         [0057]    Intervals controlled by pacer timing/control circuitry  144  include, but are not limited to, the A-A interval, A-V interval and V-V interval. The durations of these intervals are typically measured by a filtered signal from one or more sense amplifiers coupled to microprocessor  132 , and/or are set in response to programmed or stored data resident in memory  140  and communicated to pacer timing/control circuitry  144  via address/data bus  134 . Microprocessor  132  determines durations of the intervals in response to pacing parameter settings received from programmer  16 . Pacer timing/control circuitry  144  may determine the amplitude and duration of the cardiac pacing pulses, under control of microprocessor  132 . Amplitude and duration of cardiac pacing pulses are examples of additional pacing parameters that may be programmed using the techniques of the invention. In this way, microprocessor  132  and pacer timing/control circuitry  144  cooperate to provide therapeutic electrical stimulation to the heart  42  according to pacing parameter settings received from programmer  16 .  
         [0058]    As an example, during delivery of pacing therapy escape interval counters within pacer timing/control circuitry  144  are typically reset upon sensing of depolarization wavefronts as indicated by a signals on lines  114 , 118 , 122 , 126  and in accordance with the selected mode of pacing on time-out trigger generation of pacing pulses by pacer output circuitry  146 , 148 , 150 , 152 , which are coupled to electrodes  50 , 52 , 62 , 64 , 74 , 76 , 94 , 98 . Escape interval counters are also reset on generation of pacing pulses and thereby control the basic timing of cardiac pacing functions, including anti-tachyarrhythmia pacing. The durations of the intervals defined by escape interval timers are determined by microprocessor  132  via data/address bus  134 . The value of the count present in the escape interval counters when reset by sensed R-waves and P-waves may be used to measure the durations of R-R intervals, P-P intervals, P-R intervals and R-P intervals, which measurements are stored in RAM  140  and used to detect the presence of tachyarrhythmias.  
         [0059]    Microprocessor  132  may operate as an interrupt driven device, responsive to interrupts from pacer timing/control circuitry  144  corresponding to the occurrence of sensed P-waves and R-waves and corresponding to the generation of cardiac pacing pulses. Those interrupts are provided via data/address bus  134 . Any necessary mathematical calculations to be performed by microprocessor  132  and any updating of the values or intervals controlled by pacer timing/control circuitry  144  take place following such interrupts.  
         [0060]    In the event that generation of a cardioversion or defibrillation pulse is required, microprocessor  132  may employ an escape interval counter to control timing of such cardioversion and defibrillation pulses, as well as associated refractory and blanking periods, and the like. In response to the detection of atrial or ventricular fibrillation or tachyarrhythmia requiring a cardioversion pulse, microprocessor  132  activates cardioversion/defibrillation control circuitry  108 , which initiates charging of high voltage capacitors  110  via charging circuit  154 , under the control of high voltage charging control line  156 . The voltage on the high voltage capacitors is monitored via VCAP line  158 , which is passed through multiplexer  136  and in response to reaching a predetermined value set by microprocessor  132 , results in generation of a logic signal on Cap Full (CF) line  160  to terminate charging. Thereafter, timing of the delivery of the defibrillation or cardioversion pulse is controlled by pacer timing/control circuitry  144 . Following delivery of the fibrillation or tachycardia therapy microprocessor  132  returns the device to cardiac pacing mode and awaits the next successive interrupt due to pacing or the occurrence of a sensed atrial or ventricular depolarization.  
         [0061]    Delivery of cardioversion or defibrillation pulses is accomplished by output circuit  104  under the control of control circuitry  108  via control bus  106 . Output circuit  104  determines whether a monophasic or biphasic pulse is delivered, the polarity of the electrodes and which electrodes are involved in delivery of the pulse. Output circuit  104  also includes high voltage switches that control whether electrodes are coupled together during delivery of the pulse.  
         [0062]    Although FIGS. 2 and 3 depict two pace/sense electrodes per cardiac chamber, the invention is not limited to two electrodes per chamber. Rather, the invention may be applied to multi-chamber pacing in which there maybe more or fewer than two electrodes per chamber. For example, the invention may be applied to a bi-ventricular pacing system that includes a single electrode in the right ventricle, but three electrodes placed around the left ventricle, such as the left ventricular anterior-septum wall, the left ventricular lateral free wall, and the left ventricular posterior free wall.  
         [0063]    Multiple-site electrode placement with respect to a single cardiac chamber may result in more homogenous activation and homogenous mechanical response, which in turn may result in an improved hemodynamic condition for a patient. Consequently, the invention encompasses embodiments in which a single cardiac chamber is responsive to two or more pacing stimuli. In an IMD configured to deliver multiple pacing pulses to a single cardiac chamber, programmer  16  may set the pacing parameter that governs delivery of the pulses to the chamber. Timing intervals between pacing pulses in multiple-electrode systems are further examples of pacing parameters that may be programmed using the techniques of the invention.  
         [0064]    [0064]FIG. 4 is a schematic diagram illustrating an exemplary external device to sense the hemodynamic operation of the heart of patient  20  and to generate one or more piece of hemodynamic data as a function of sensed hemodynamic operation. Impedance monitor  162  measures transthoracic impedance, i.e., the impedance across the chest or thorax of patient  20 . Impedance monitor  162  is connected to patient  20  via electrodes  166 A and  166 B and leads  164 A and  164 B. Impedance monitor  162  measures transthoracic impedance by, e.g., measuring the voltage developed between electrodes  166 A and  166 B when a known current is applied.  
         [0065]    Clinical data have shown that transthoracic impedance varies as a function of cardiac output. In general, an increase in cardiac output results in a decrease in transthoracic impedance, and vice versa. Because transthoracic impedance may vary as a function of other physiological factors such as patient ventilation, impedance monitor  162  ordinarily includes circuitry to filter or otherwise process signals received via electrodes  166 A and  166 B, to identify physiological factors of interest and ignore other physiological factors.  
         [0066]    In response to pacing administered by IMD  18  (not shown in FIG. 4) according to pacing parameter settings, the cardiac output of patient  20  may increase, decrease or stay substantially the same. By measuring changes in transthoracic impedance, impedance monitor  162  monitors changes in cardiac output (or stroke volume). Impedance monitor  162  generates a datum that reflects cardiac output, and supplies that datum to programmer  16 . The datum may include a measurement of impedance magnitude, phase angle, resistance, reactance, or any other index that reflects cardiac output. Programmer  16  may, in turn, program a new pacing parameter setting as a function of the datum and may supply the setting to IMD  18 . Thereafter, impedance monitor  162  monitors the transthoracic impedance of patient  20  in response to pacing therapy administered by IMD  18  according to the new pacing parameter setting. Also, as previously mentioned, the operation of monitor  162  may be coordinated with the operation or physiologic sensing capabilities of the IMD  18 .  
         [0067]    [0067]FIGS. 5A and 5B show an electrocardiogram  167  illustrating an exemplary relation between an exemplary hemodynamic datum  171 , namely, a cardiac output (CO) or stroke volume measurement, and an exemplary pacing parameter, namely, a V-V interval. FIGS. 5A and 5B depict the timing of a right ventricular pace (RVP)  168  and a left ventricular pace (LVP)  170  with different pacing parameter settings. The use of CO as a hemodynamic datum is for purpose of illustration, and the invention may be practiced with any other indicator of hemodynamic operation and/or mechanical function substantially as set forth in the Summary of this disclosure.  
         [0068]    In FIG. 5A, the V-V interval is substantially zero, meaning that IMD  18  delivers RVP  168 A and LVP  170 A at substantially the same time. Although a coordinated activation of the ventricles generally results in good hemodynamic performance, a simultaneous delivery of right- and left-ventricular paces does not necessarily produce coordinated mechanical function and good hemodynamic performance. In FIG. 5A, the exemplary hemodynamic datum  171 A shows that the cardiac output of the patient is about 4.5 liters per minute when the V-V interval is zero.  
         [0069]    Upon receiving the hemodynamic datum  171 A, programmer  16  resets the V-V interval, and IMD  18  paces the heart according to the new pacing parameter setting. The results of pacing according to the new pacing parameter setting are shown in FIG. 5B. In FIG. 5B, IMD  18  delivers RVP  168 B and LVP  170 B separated by a time interval, with LVP  170 B preceding RVP  168 B. In FIG. 5B, the exemplary hemodynamic datum  171 B shows that the cardiac output of the patient is about five liters per minute when the heart is paced according to the new pacing parameter setting, which is a substantial improvement in cardiac output.  
         [0070]    [0070]FIG. 6 is a flow diagram illustrating example techniques of the invention. For purposes of FIG. 6, it is assumed that external device  14 , programmer  16  and IMD  18  are separate components. At the outset, programmer  16  sets a pacing parameter to an initial setting ( 172 ). This initial setting could be a standard default setting, or the initial setting could be a function of patient characteristics, patient history, history of pacing parameters, history of responses to pacing parameters or the like. Programmer  16  transmits the pacing parameter setting to IMD  18  ( 174 ), which receives the setting ( 176 ).  
         [0071]    In response, IMD  18  paces the heart of patient  20  according to the pacing parameter setting ( 176 ). In particular, IMD  18  sets or adjusts pacing parameters in accordance with the pacing parameter setting. Pacing in this fashion may continue for several minutes. The cardiovascular system of patient  20 , particularly the hemodynamic operation of the heart of patient  20 , responds to the pacing over a period of time. As a result, according to the present invention an interval of time (e.g., a number of cardiac cycles or timed period) allows for the patient to respond to the new pacing parameters before attempting to measure the effect on hemodynamic and/or cardiac mechanical performance. Those skilled in the art will appreciate that acute measurements (e.g., stroke volume) may be used to adjust pacing parameters as well as chronic measurements (e.g., cardiac output, or trend information collected over a period of hours, days or weeks).  
         [0072]    External device  14  monitors the response, measuring the effect or effects of the pacing parameter setting on patient  20 . The device generates at least one hemodynamic datum that reflects the response of patient  20  ( 180 ). External device  14  transmits the hemodynamic datum to programmer  16  ( 182 ), which receives the hemodynamic datum ( 184 ).  
         [0073]    In FIG. 6, it is assumed that the hemodynamic datum is unsatisfactory or that further adjustment of one or more pacing parameter may be desired. Accordingly, programmer  16  sets a second pacing parameter as a function of the hemodynamic datum ( 186 ), and transmits the second pacing parameter to IMD  18  ( 188 ), which receives the second pacing parameter ( 190 ). IMD  18  paces the heart of patient  20  according to the second pacing parameter ( 192 ).  
         [0074]    External device  14 , programmer  16  and IMD  18  may repeat this process, measuring the effect or effects of various pacing parameter settings, setting new pacing parameter settings, and pacing the heart according to a new pacing parameter settings. When external device  14  generates a hemodynamic datum indicating that the hemodynamic operation of the patient is satisfactory, programmer  16  discontinues setting new pacing parameter settings. Instead, programmer  16  selects a pacing parameter setting that produced the desired or most beneficial results, and IMD  18  implements the selected pacing parameter setting.  
         [0075]    In this way, external device  14 , programmer  16  and IMD  18  cooperate to find a set of pacing parameter settings that benefit the patient. Programmer  16  programs IMD  18  with a pacing parameter setting, and receives feedback from hemodynamic measurement device  14  that indicates the effectiveness of the pacing parameter setting. In this way, more effective settings and less effective settings can be identified, and more effective settings can be put into practice.  
         [0076]    A number of embodiments of the invention have been described. The invention can be practiced with embodiments other than those disclosed, however. For example, telemetric communication between the device  14  and the IMD  18  may be used to enhance the pacing parameter settings provided by the programmer  16 . In addition, although the techniques of the invention are described above as being implemented without human intervention, the invention may also be practiced under the supervision of a clinician. Programmer  16  may receive, for example, input from a clinician in addition to feedback from external device  14  and IMD  18 . In addition, the clinician may set the standards for what hemodynamic data indicate more effective hemodynamic operation or less effective hemodynamic operation.  
         [0077]    The invention may be embodied as a computer-readable medium that includes instructions for causing a programmable processor, such as processor  28  shown in FIG. 1 pacer timing/control circuitry  144  shown in FIG. 3, to carry out the methods described above. The programmable processor may include one or more individual processors, which may act independently or in concert. A “computer-readable medium” includes but is not limited to read-only memory, Flash memory and a magnetic or optical storage medium. The instructions may be implemented as one or more software modules, which may be executed by themselves or in combination with other software. These and other embodiments are within the scope of the following claims.