Abstract:
Heart stimulating system for stimulating at least a ventricle of a heart including: stimulation pulse generator adapted to generate stimulation pulses and connected to a ventricular stimulation electrode for delivering stimulation pulses, atrial sensing stage connected to an electrode for picking up potentials inside an atrium and adapted to sense an excitation or contraction of atrial myocardium, ventricular sensing stage connected to an electrode for picking up potentials inside a ventricle and adapted to sense an excitation or contraction of ventricular myocardium, memory for AV-delay values, a control unit adapted to trigger said stimulation pulse generator to generate ventricular stimulation pulses timed based on AV-delay values stored in said memory and to acquire atrioventricular interval samples, and atrioventricular interval timing analyzing unit for receiving atrioventricular interval samples from said control unit and adapted to generate at least one histogram based on said atrioventricular interval samples and analyze said histograms.

Description:
BACKGROUND OF THE INVENTION 
       [0001]    1. Field of the Invention 
         [0002]    The invention refers to a heart stimulation system for stimulating at least one chamber of a heart by means of electrical stimulation pulses that are delivered when a delay time started by a cardiac event expires. The invention particularly refers to implantable medical devices such as implantable pacemakers and implantable cardioverter/defibrillators for atrial synchronous stimulation of a ventricle of a heart. 
         [0003]    2. Description of the Related Art 
         [0004]    Implantable heart stimulators can be used for cardiac rhythm management (CRM) for treating a variety of heart functional and rhythm disorders including but not limited to bradycardia, tachycardia or fibrillation by way of electric stimulation pulses delivered to the heart tissue, the myocardium. A sufficiently strong stimulation pulse outside a heart chamber&#39;s refractory period leads to excitation of the myocardium of that heart chamber, which in turn is followed by a contraction of the respective heart chamber. 
         [0005]    Depending on the disorder to be treated, such heart stimulator generates electrical stimulation pulses that are delivered to the heart tissue (myocardium) of a respective heart chamber according to an adequate timing regime. Delivery of stimulation pulses to the myocardium is usually achieved by means of an electrode lead that is electrically connected to a stimulation pulse generator inside a heart stimulator&#39;s housing and that carries a stimulation electrode in the region of its distal end. A stimulation pulse also is called a pace. Similarly, pacing a heart chamber means stimulating a heart chamber by delivery of a stimulation pulse. 
         [0006]    In order to be able to sense the contraction a heart chamber which occurs naturally without artificial stimulation and which is called an intrinsic contraction, the heart stimulator usually includes at least one sensing stage that is connected to a sensing electrode and said electrode is placed in or near the heart chamber. An intrinsic excitation of a heart chamber results in characteristic electrical potentials that can be picked up via the sensing electrode and that can be evaluated by the sensing stage in order to determine whether an intrinsic excitation—called: intrinsic event—has occurred. 
         [0007]    Usually, a heart stimulator features separate stimulation pulse generators for each heart chamber to be stimulated. Therefore, in a dual chamber pacemaker, usually an atrial and a ventricular stimulation pulse generator for generating atrial and ventricular stimulation pulses are provided. Delivery of an atrial or a ventricular stimulation pulse causing an artificial excitation of the atrium or the ventricle, respectively, is called an atrial stimulation event A P  (atrial paced event) or a ventricular stimulation event V P  (ventricular paced event), respectively. 
         [0008]    Similarly, common heart stimulators feature separate sensing stages for each heart chamber to be of interest. In a dual chamber pacemaker usually two separate sensing stages, an atrial sensing stage and a ventricular sensing stage, are provided that are capable to detect intrinsic atrial events A S  (atrial sensed event) or intrinsic ventricular events V S  (ventricular sensed event), respectively. 
         [0009]    As known in the art, separate sensing and pacing stages are provided for three-chamber (right atrium RA, right ventricle RV, left ventricle LV) or four-chamber (right atrium RA, left atrium LA, right ventricle RV, left ventricle LV) pacemakers or ICDs. 
         [0010]    By means of a sensing stage for a heart chamber to be stimulated, the pacemaker is able to only trigger stimulation pulses when needed that is when no intrinsic excitation of the heart chamber occurs in the allotted time. Such mode of pacing a heart chamber is called demand mode. In the demand mode the pacemaker schedules an atrial or a ventricular escape interval that causes triggering of an atrial or ventricular stimulation pulse when the escape interval times out. Otherwise, if an intrinsic atrial or ventricular event is detected prior to time out of the respective atrial or ventricular escape interval, triggering of the atrial or ventricular stimulation pulse is inhibited. Such intrinsic (natural, non-stimulated) excitations are manifested by the occurrence of recognizable electrical signals that accompany the excitation and depolarization of a cardiac muscle tissue (myocardium). The depolarization of the myocardium is usually immediately followed by a cardiac contraction. For the purpose of the present application, depolarization and contraction may be considered tightly coupled events and the terms “depolarization” and “contraction” are used herein as synonyms. 
         [0011]    In a heart cycle, an excitation of the myocardium leads to a depolarization of the myocardium that leads to a contraction of the heart chamber. If the myocardium is fully depolarized it is unsusceptible for further excitation and is thus refractory. Thereafter, the myocardium repolarizes and thus relaxes and the heart chamber expands again. In a typical intracardiac electrogram (iEGM) depolarization of the ventricle corresponds to a signal known as the “R-wave”. The repolarization of the ventricular myocardium coincides with a signal known as the “T-wave”. Atrial depolarization is manifested by a signal known as the “P-wave”. 
         [0012]    A natural contraction of a heart chamber can be similarly detected by the evaluating electrical signals sensed by the sensing channels. In the sensed electrical signal the depolarization of an atrium muscle tissue is manifested by occurrence of a P-wave. Similarly, the depolarization of ventricular muscle tissue is manifested by the occurrence of a R-wave. The detection of a P-wave or a R-wave signifies the occurrence of intrinsic atrial, As, or ventricular, Vs events, respectively. 
         [0013]    Several modes of operation are available in state of the art multimode cardiac stimulation systems. The modes of operation are concerned with which chambers of the heart are monitored for native activity; which chambers of the heart are provided with pacing therapy; and which cardiac functions are treated: inter-chamber conduction (AV Node, nodal disease); chronotropy (sinus node, sinus disease); and intra-chamber conduction (bundle branch delays and blocks, conduction disorders). The operational modes of a stimulation system, single, dual or multi-chamber devices, are classified using a standard descriptive code. This invention covers the automatic characterization and determination of the timing objectives for managing inter-chamber and intra-chamber disorders. 
         [0014]    The NBG code system is used to describe these modes of operations. In such a code, the first three letters describe the primary configuration. The First letter identifies the chamber of the heart that is paced (i.e., that chamber where a stimulation pulse is delivered), with a “V” indicating the ventricle, an “A” indicating the atrium, and a “D” indicating both the atrium and ventricle. The second letter of the code identifies the chamber wherein cardiac activity is sensed, using the same letters, and wherein an “O” indicates no sensing occurs. The third letter of the code identifies the action or response that is taken by the pacemaker. In general, three types of action or responses are recognized: (1) an Inhibiting (“I”) response wherein a stimulation pulse is delivered to the designated chamber at the conclusion of the appropriate escape interval unless cardiac activity is sensed during the escape interval, in which case the stimulation pulse is inhibited; (2) a Trigger (“T”) response wherein a stimulation pulse to a prescribed chamber of the heart following a prescribed period of time after a sensed event; or (3) a Dual (“D”) response wherein both the Inhibiting mode and Trigger mode may be evoked, e.g., with the “inhibiting” occurring in one chamber of the heart and the “triggering” in the other. 
         [0015]    To the primary three-letter code, a fourth letter “R” may optionally be added to designate a rate-responsive pacemaker and/or whether the rate-responsive features of such a rate-responsive pacemaker are enabled (“O” typically being used to designate that rate-responsive operation has been disabled). A rate-responsive pacemaker is one wherein a specified parameter or combination of parameters, such as physical activity, the amount of oxygen in the blood, the temperature of the blood, etc., is sensed with an appropriate sensor and is used as a physiological indicator of what the pacing rate should be. When enabled, such rate-responsive pacemaker thus provides stimulation pulses that best meet the physiological demands of the patient. 
         [0016]    To the fore mentioned first 4-letter code, a fifth code field may be added to designate the inter-chamber configuration. 
         [0017]    A dual chamber pacemaker featuring an atrial and a ventricular sensing stage and an atrial and a ventricular stimulation pulse generator can be operated in a number of stimulation modes like VVI, wherein atrial sense events are ignored and no atrial stimulation pulses are generated, but only ventricular stimulation pulses are delivered in a demand mode, AAI, wherein ventricular sense events are ignored and no ventricular stimulation pulses are generated, but only atrial stimulation pulses are delivered in a demand mode, or DDD, wherein both, atrial and ventricular stimulation pulses are delivered in a demand mode. In such DDD mode of pacing, ventricular stimulation pulses can be generated in synchrony with sensed intrinsic atrial events and thus in synchrony with an intrinsic atrial rate, wherein a ventricular stimulation pulse is scheduled to follow an intrinsic atrial contraction after an appropriate atrioventricular delay (AV-delay; AVD), thereby maintaining the hemodynamic benefit of atrioventricular synchrony. 
         [0018]    The AV-delay determines the chronological relation between an atrial event and a prescribed point of time of a ventricular event, the ventricular escape interval. 
         [0019]    Since an optimal AV-delay may vary for different heart rates or stimulation rates and may even vary from patient to patient, the AV-delay usually is adjustable. 
         [0020]    In order to promote natural ventricular events, often the ventricular escape interval is extended by a short time interval thus resulting in a prolonged ventricular escape interval called “AV hysteresis interval” 
       BRIEF SUMMARY OF THE INVENTION 
       [0021]    It is an object of the invention to provide a heart stimulating system that provides for an appropriate yet simple setting of the AV-delay timing. 
         [0022]    According to the present invention the object of the invention is achieved by a heart stimulator featuring: 
         [0023]    a stimulation pulse generator adapted to generate electric stimulation pulses and being connected or being connectable to at least a ventricular stimulation electrode for delivering electric stimulation pulses to at least said ventricle of the heart, 
         [0024]    a sensing stage connected or being connectable to an electrode for picking up electric potentials inside at least said ventricle of a heart, said sensing stage being adapted to sense an excitation or a contraction of a heart chamber, 
         [0025]    a sensing stage connected or being connectable to an electrode for picking up electric potentials inside at least an atrium of a heart, said sensing stage being adapted to sense an excitation or a contraction of a heart chamber, 
         [0026]    a memory for AV-delay values, 
         [0027]    a control unit that is connected to said memory, said sensing stage and to said stimulation pulse generator, said control unit being adapted to trigger said stimulation pulse generator to generate ventricular stimulation pulses that are timed based on AV-delay values stored in said memory, 
         [0028]    and an atrioventricular interval timing analyzing unit that is part of said control unit or that is connected to said control unit for receiving atrioventricular interval timing data from said control unit and that is adapted to 
         [0029]    generate histograms based on said atrioventricular interval timing data received from said control unit and 
         [0030]    analyze said histograms to determine at least one particular quantile atrioventricular interval that is a m th  q-quantile of the atrioventricular interval distribution as manifested by the counts in said histograms. 
         [0031]    Generally, quantiles are points taken at regular intervals from the cumulative distribution function of a random variable that in the present case is the cumulative distribution of the measured intrinsic atrioventricular conduction times. Dividing ordered atrioventricular interval data into q essentially equal-sized data subsets is the motivation for q-quantiles. The quantile points are the data values marking the boundaries between consecutive subsets. If the ordered atrioventricular interval data were divided into 100 essentially equal-sized data subsets (q=100), the boundaries between these subsets would be the percentile points (1 through 99). The median AV interval would be a member of the 50 th  percentile; or the m th  q-quantile with m=q/2. The 50 th  percentile corresponds to the atrioventricular interval that is in the middle of the ordered sequence of atrioventricular intervals where one half of all recorded atrioventricular intervals are longer than the median atrioventricular interval and the other half is shorter than the median atrioventricular interval. 
         [0032]    Preferably the atrioventricular interval timing analyzing unit is adapted to determine a specific m th  q-quantile for a distribution of atrioventricular intervals. The m th  quantile is the upper boundary of the subset, which includes the indicated AV interval. This subset includes the atrioventricular interval sample for which at least m/q (with 0&lt;m&lt;q) are shorter. 
         [0033]    According to one preferred embodiment of the heart stimulating system the atrioventricular interval timing analysis unit is adapted to determine the median atrioventricular interval as defined above. 
         [0034]    According to a further preferred embodiment of the heart stimulating system the atrioventricular interval timing analysis unit is adapted to determine an upper limit native atrioventricular conduction time, e.g. to the 97th percentile of at least a part of ordered recorded atrioventricular intervals. 
         [0035]    The sensing stages, the stimulation pulse generators, the control unit and the memory for AV delay values are part of an implantable heart stimulator and are integrated into the heart stimulator&#39;s housing. The heart stimulator can be an implantable pacemaker or an implantable cardioverter/defibrillator or a combination of both. 
         [0036]    The atrioventricular interval timing analyzing unit can be integrated into a housing of the implantable heart stimulator and can be a part of the unit. 
         [0037]    Alternatively, the atrioventricular interval timing analyzing unit can be part of an external device that can be wirelessly connected to the implantable heart stimulator. The external device may be a patient device used for home monitoring purposes, or a central service center, that can be connected to the implantable heart stimulator via an external device next to the implantable heart stimulator or it can be a programmer used for wireless programming of the implantable heart stimulator. Making the atrioventricular interval timing analyzing unit part of an external device that eventually is connected to the implantable heart stimulator is a valid option, since it usually is sufficient to analyze atrioventricular conduction (AV conduction) and the duration of natural (intrinsic) atrioventricular intervals only from time to time. Thus higher order processing demanding adequate resources can easily be sourced out from the implantable heart stimulator to an external device. 
         [0038]    Preferably, the atrioventricular interval timing analysis unit is further adapted to confirm sufficient atrioventricular conduction prior to generating a hysteresis AV delay value and not to generate a hysteresis AV delay value if no sufficient atrioventricular conduction is confirmed. In order to confirm sufficient atrioventricular conduction the atrioventricular interval timing analysis unit is preferably adapted to compare the number of intrinsic ventricular events Vs to the total number of ventricular events (Vs+Vp) within a predetermined time window. Preferably, sufficient atrioventricular conduction is confirmed if more than a specified minimal fraction (e.g. 3%) of all ventricular events are intrinsic events. 
         [0039]    The object of the invention is achieved by a method for atrioventricular timing analysis and atrioventricular interval adjustment; said method comprises the steps of:
       acquisition of atrioventricular interval timing data,   generation of histograms comprising bins wherein each bin is associated to dedicated range of atrioventricular intervals, and   determination of at least one m th  q-quantile atrioventricular interval.       
 
         [0043]    Preferably, the m th  q-quantile atrioventricular interval is a median atrioventricular interval. 
         [0044]    In a preferred embodiment, the method includes the step of generating an AV-delay value to be said median atrioventricular interval minus a predetermined time interval, which compensates for the stimulation latency. The predetermined time interval preferably has a duration of 10 to 40 ms, e.g. 20 ms. 
         [0045]    Similarly it is preferred that the method includes the step of generating an hysteresis AV delay value corresponding to the m th  q-quantile atrioventricular interval with m being equal to or larger than 97% of q. 
         [0046]    In a further preferred embodiment the method includes the steps of
       Accumulating and analyzing atrioventricular intervals recorded over at least 24-hr, using a long AV delay of 250 ms to 300 ms for ventricular stimulation.   Checking for evidence of native (natural) atrioventricular conduction leading to intrinsic ventricular events Vs.
           If no evidence of native AV conduction is found, in particular if less than specified minimum fraction (e.g. 3%) of all recorded ventricular events are intrinsic ventricular events, then programming standard AV delay values into the AV delay memory and do not enable AV hysteresis   If sufficient evidence of native AV conduction are found, in particular if equal to or more than a specified minimum fraction of (e.g. 3%) of all recorded ventricular events are intrinsic ventricular events, then
               determining a longer edge for the distributions of recorded atrioventricular intervals, e.g. the quantile that forms the upper threshold (e.g. 97 th  percentile) of the recorded atrioventricular intervals,   calculating the atrial sense latency time   programming the hysteresis AV delay to include the longer edge of the distribution of recorded atrioventricular intervals, e.g. the 97-th percentile interval,   programming a short ApVp delay as follows:
                   preserving the AV hysteresis timing as constrained by the device&#39;s AV hysteresis options   targeting the short AV delay to be shorter than the median ApVs interval by an amount equivalent to the stimulation latency, e.g. 20 ms.   constraining the AV delay to be no shorter than 150 ms at &lt;70 ppm.   
                   
               
               
 
         [0058]    Automatic AV delay initialization and automatic atrial sense latency compensation facilitates the management of the AV timing parameters while promoting native conduction in the CRM patient population. 
         [0059]    These objectives are achieved by a heart stimulating system and a method that provides for automatic or device assisted initialization of AV delay values as follows:
       On implant detection, enable AV Hysteresis and collect 24-hr AV conduction statistics.   If sufficient native sinus activity, configure the Atrial Sense Latency Compensation.   If sufficient native AV conduction, customize the AV Delay and dynamics.   If sufficient and acceptable AV conduction, enable AV Hysteresis.       
 
         [0064]    Furthermore, the heart stimulation system and the method can provide follow-up recommendations as follows:
       Automatically review event counters and AV conduction statistics   On user request recommend AV timing parameters.       
 
         [0067]    It is to be appreciated that features of preferred embodiments of the invention may be combined in any useful manner thus arriving a further preferred embodiments of the invention not explicitly mentioned in this disclosure. 
     
    
     
       BRIEF DESCIPTION OF THE DRAWINGS 
         [0068]    The above and other aspects, features and advantages of the present invention will be more apparent from the following more particular description thereof, presented in conjunction with the following drawings wherein: 
           [0069]      FIG. 1  shows a dual chamber pacemaker connected to leads placed in a heart. 
           [0070]      FIG. 2  is a block diagram of a heart stimulator according to the invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0071]    The following description is of the best mode presently contemplated for carrying out the invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles of the invention. The scope of the invention should be determined with reference to the claims. 
         [0072]    In  FIG. 1  a dual chamber pacemaker  10  as heart stimulator connected to pacing/sensing leads placed in a heart  12  is illustrated. The pacemaker  10  is electrically coupled to heart  12  by way of leads  14  and  16 . Lead  14  has a pair of right atrial electrodes  18  and  20  that are in contact with the right atria  26  of the heart  12 . Lead  16  has a pair of electrodes  22  and  24  that are in contact with the right ventricle  28  of heart  12 . Electrodes  18  and  22  are tip-electrodes at the very distal end of leads  14  and  16 , respectively. Electrode  18  is a right atrial tip electrode RA-Tip and electrode  22  is a right ventricular tip electrode RV-Tip  22 . Electrodes  20  and  24  are ring electrodes in close proximity but electrically isolated from the respective tip electrodes  18  and  22 . Electrode  20  forms a right atrial ring electrode RA-Ring and electrode  24  forms a right ventricular ring electrode RV-Ring. 
         [0073]    Referring to  FIG. 2  a simplified block diagram of a dual chamber pacemaker  10  is illustrated. During operation of the pacemaker leads  14  and  16  are connected to respective output/input terminals of pacemaker  10  as indicated in  FIG. 1  and carry stimulating pulses to the electrode pairs  18 ,  20  and  22 ,  24  from an atrial stimulation pulse generator A-STIM  32  and a ventricular pulse generator V-STIM  34 , respectively. Further, electrical signals from the atrium are carried from the electrode pair  18  and  20 , through the lead  14 , to the input terminal of an atrial channel sensing stage A-SENS  36 ; and electrical signals from the ventricles are carried from the electrode pair  22  and  24 , through the lead  16 , to the input terminal of a ventricular sensing stage V-SENS  38 . 
         [0074]    Controlling the dual chamber pacer  10  is a control unit CTRL  40  that is connected to sensing stages A-SENS  36  and V-SENS  38  and to stimulation pulse generators A-STIM  32  and V-STIM  34 . Control unit CTRL  40  receives the output signals from the atrial sensing stage A-SENS  36  and from the ventricular sensing stage V-SENS  38 . The output signals of sensing stages A-SENS  36  and V-SENS  38  are generated each time that a P-wave representing an intrinsic atrial event or an R-wave representing an intrinsic ventricular event, respectively, is sensed within the heart  12 . An As-signal is generated, when the atrial sensing stage A-SENS  36  detects a P-wave and a Vs-signal is generated, when the ventricular sensing stage V-SENS  38  detects an R-wave. 
         [0075]    Control unit CTRL  40  also generates trigger signals that are sent to the atrial stimulation pulse generator A-STIM  32  and the ventricular stimulation pulse generator V-STIM  34 , respectively. These trigger signals are generated each time that a stimulation pulse is to be generated by the respective pulse generator A-STIM  32  or V-STIM  34 . The atrial trigger signal is referred to simply as the “A-pulse”, and the ventricular trigger signal is referred to as the “V-pulse”. During the time that either an atrial stimulation pulse or ventricular stimulation pulse is being delivered to the heart, the corresponding sensing stage, A-SENS  36  and/or V-SENS  38 , is typically disabled by way of a blanking signal presented to these amplifiers from the control unit CTRL  40 , respectively. This blanking action prevents the sensing stages A-SENS  36  and V-SENS  38  from becoming saturated from the relatively large stimulation pulses that are present at their input terminals during this time. This blanking action also helps prevent residual electrical signals present in the muscle tissue as a result of the pacer stimulation from being interpreted as P-waves or R-waves. 
         [0076]    Control unit CTRL  40  comprises circuitry for timing ventricular and/or atrial stimulation pulses according to an adequate stimulation rate that can be adapted to a patient&#39;s hemodynamic need as pointed out below. 
         [0077]    Still referring to  FIG. 2 , the pacer  10  includes a memory circuit MEM  42  that is coupled to the control unit CTRL  40  over a suitable data/address bus ADR  44 . This memory circuit MEM  42  allows certain control parameters, used by the control unit CTRL  40  in controlling the operation of the pacemaker  10 , to be programmably stored and modified, as required, in order to customize the pacemaker&#39;s operation to suit the needs of a particular patient. Such data includes the basic timing intervals used during operation of the pacemaker  10  and AV delay values and hysteresis AV delay values in particular. 
         [0078]    Further, data sensed during the operation of the pacemaker may be stored in the memory MEM  42  for later retrieval and analysis. This includes atrioventricular interval data that are acquired by the control unit CTRL  40 . Control unit CTRL  40  is adapted to determine the atrioventricular interval data as required for automatic atrioventricular interval analysis by determining the time interval between an atrial event, either sensed (As) or stimulated (Ap) and an immediately following ventricular sensed event Vs as indicated by the ventricular sensing stage V-SENS  38 . 
         [0079]    A telemetry circuit TEL  46  is further included in the pacemaker  10 . This telemetry circuit TEL  46  is connected to the control unit CTRL  40  by way of a suitable command/data bus. Telemetry circuit TEL  46  allows for wireless data exchange between the pacemaker  10  and some remote programming or analyzing device which can be part of a centralized service center serving multiple pacemakers. 
         [0080]    The pacemaker  10  in  FIG. 1  is referred to as a dual chamber pacemaker because it interfaces with both the right atrium  26  and the right ventricle  28  of the heart  12 . Those portions of the pacemaker  10  that interface with the right atrium, e.g., the lead  14 , the P-wave sensing stage A-SENSE  36 , the atrial stimulation pulse generator A-STIM  32  and corresponding portions of the control unit CTRL  40 , are commonly referred to as the atrial channel. Similarly, those portions of the pacemaker  10  that interface with the right ventricle  28 , e.g., the lead  16 , the R-wave sensing stage V-SENSE  38 , the ventricular stimulation pulse generator V-STIM  34 , and corresponding portions of the control unit CTRL  40 , are commonly referred to as the ventricular channel. 
         [0081]    In order to allow rate adaptive pacing in a DDDR or a DDIR mode, the pacemaker  10  further includes a physiological sensor ACT  48  that is connected to the control unit CTRL  40  of the pacemaker  10 . While this sensor ACT  48  is illustrated in  FIG. 2  as being included within the pacemaker  10 , it is to be understood that the sensor may also be external to the pacemaker  10 , yet still be implanted within or carried by the patient. A common type of sensor is an activity sensor, such as a piezoelectric crystal, mounted to the case of the pacemaker. Other types of physiologic sensors are also known, such as sensors that sense the oxygen content of blood, respiration rate, blood pH, intra-cardiac impedance changes, and the like. The type of sensor used is not critical to the present invention. Any sensor capable of sensing some physiological parameter relatable to the rate at which the heart should be beating can be used. Such sensors are commonly used with “rate-responsive” pacemakers in order to adjust the rate of the pacemaker in a manner that tracks the physiological needs of the patient. 
         [0082]    The control unit CTRL  40  is adapted to determine an adequate heart rate or stimulation rate in any manner known as such. Furthermore, control unit CTRL  40  is adapted to apply AV delay values stored in an AV-delay value memory that is part of memory MEM  42  for atrium synchronous stimulation of the ventricle of the heart and—if applicable—a hysteresis AV delay. 
         [0083]    With respect to AV-delay optimization, an atrioventricular interval timing analyzing unit is provided that is either a part of control unit CTRL  40  or that is connected to the control unit. 
         [0084]    Atrioventricular Interval Data Collection: 
         [0085]    The atrioventricular interval timing analyzing unit is adapted to accumulate instances of AV conduction intervals in the corresponding timing bins for the associated event sequences (AsVs or ApVs) and heart rate band. 
         [0086]    The atrioventricular interval timing analyzing unit is adapted to classify atrioventricular intervals including AsVs and ApVs intervals that is intervals between an intrinsic atrial excitation As and an intrinsic ventricular excitation Vs and a stimulated atrial excitation Ap and an intrinsic ventricular excitation Vs, respectively. Atrioventricular timing information required for that evaluation is received from the control unit CTRL  40 . 
         [0087]    If a stable heart rhythm is present, the atrioventricular interval timing analyzing unit is adapted to sort all atrioventricular intervals into  10  histograms. A first group of histograms is set up for collecting AsVs intervals and a second group of histogram is set up for collecting ApVs intervals. 
         [0088]    Both groups of histograms comprise 5 histograms each one being assigned to a different frequency band of heart rates, namely heart rates below 70 ppm, heart rates in the range from 70 to 89 ppm, heart rates in the range from 90 to 109 ppm, heart rates in the range from 110 to 129 ppm, and heart rates equal to or higher than 130 ppm. 
         [0089]    Each histogram comprises 26 bins wherein each bin corresponds to a range in atrioventricular intervals. In a first bin a count of all the atrioventricular intervals shorter than 102 ms are accumulated. All further 25 bins cover a range of 7.8 ms, see the table below: 
         [0000]    
       
         
               
               
               
               
               
             
           
               
                   
                   
               
             
             
               
                   
                  1 st  bin 
                   
                   
                 to &lt;102 ms 
               
               
                   
                  2 nd  bin 
                 from 
                 102 ms 
                 to &lt;109.8 ms 
               
               
                   
                  3 rd  bin 
                 from 
                 109.8 ms 
                 to &lt;117.6 ms 
               
               
                   
                  4 th  bin 
                 from 
                 117.6 ms 
                 to &lt;125.4 ms 
               
               
                   
                  5 th  bin 
                 from 
                 125.4 ms 
                 to &lt;133.2 ms 
               
               
                   
                  6 th  bin 
                 from 
                 133.2 ms 
                 to &lt;141 ms 
               
               
                   
                  7 th  bin 
                 from 
                 141 ms 
                 to &lt;148.8 ms 
               
               
                   
                  8 th  bin 
                 from 
                 148.8 ms 
                 to &lt;156.6 ms 
               
               
                   
                  9 th  bin 
                 from 
                 156.6 ms 
                 to &lt;164.4 ms 
               
               
                   
                 10 th  bin 
                 from 
                 164.4 ms 
                 to &lt;172.2 ms 
               
               
                   
                 11 th  bin 
                 from 
                 172.2 ms 
                 to &lt;180 ms 
               
               
                   
                 12 th  bin 
                 from 
                 180 ms 
                 to &lt;187.8 ms 
               
               
                   
                 13 th  bin 
                 from 
                 187.8 ms 
                 to &lt;195.6 ms 
               
               
                   
                 14 th  bin 
                 from 
                 195.6 ms 
                 to &lt;203.4 ms 
               
               
                   
                 15 th  bin 
                 from 
                 203.4 ms 
                 to &lt;211.2 ms 
               
               
                   
                 16 th  bin 
                 from 
                 211.2 ms 
                 to &lt;219 ms 
               
               
                   
                 17 th  bin 
                 from 
                 219 ms 
                 to &lt;226.8 ms 
               
               
                   
                 18 th  bin 
                 from 
                 226.8 ms 
                 to &lt;234.6 ms 
               
               
                   
                 19 th  bin 
                 from 
                 234.6 ms 
                 to &lt;242.4 ms 
               
               
                   
                 20 th  bin 
                 from 
                 242.4 ms 
                 to &lt;250.2 ms 
               
               
                   
                 21 st  bin 
                 from 
                 250.2 ms 
                 to &lt;258 ms 
               
               
                   
                 22 nd  bin 
                 from 
                 258 ms 
                 to &lt;265.8 ms 
               
               
                   
                 23 rd  bin 
                 from 
                 265.8 ms 
                 to &lt;273.6 ms 
               
               
                   
                 24 th  bin 
                 from 
                 273.6 ms 
                 to &lt;281.4 ms 
               
               
                   
                 25 th  bin 
                 from 
                 281.4 ms 
                 to &lt;289.2 ms 
               
               
                   
                 26 th  bin 
                 from 
                 289.2 ms 
                 to &lt;297 ms 
               
               
                   
                   
               
             
          
         
       
     
         [0090]    The width of the first AsVs bin, &lt;102 ms, is 86 ms wide. The width of the first ApVs bin, &lt;102 ms, is less than 7.8 ms wide, because the safety window usually triggers a ventricular pace at 100 ms and the device reclassifies the AV sequence as ApVp. 
         [0091]    Atrioventricular Timing Analysis: 
         [0092]    The atrioventricular interval timing analyzing unit is further adapted to determine whether or not a stable atrio-ventricular sequential rhythm is present for more than 75% of a predetermined time window that includes a plurality of heart cycles. Only if such stable heart rhythm is present, the determined atrioventricular intervals are evaluated or even accumulated in the histograms. 
         [0093]    The atrioventricular interval timing analyzing unit is adapted to determine the presence of a stable heart rhythm by comparing the number of atrial events with the number of ventricular event in the predetermined time window. If the number of atrial events exceeds the number of ventricular events by more than 25%, no stable (that is, an instable) heart rhythm is determined. The atrioventricular interval timing analyzing unit is further adapted to determine the number of pairs of immediately consecutive ventricular events (that is pairs of ventricular events with no intermediate atrial event) and to compare that number to the number of ventricular events in the predetermined time window. If the number of pairs of immediately consecutive ventricular events exceeds 25% of the number of ventricular events in the predetermined time window no stable atrio-ventricular sequential rhythm is determined. 
         [0094]    Furthermore, the atrioventricular interval timing analyzing unit is adapted to check for a presence of a third degree AV block. If the sum of all AsVs and ApVs events is less the 0.03 times the number of all AV events (including i.e. ApVp and AsVp events), no evaluation of atrioventricular intervals is performed. 
         [0095]    In addition to the previous conditions, no evaluation of atrioventricular intervals is performed on an AV conduction histogram if the combined bins contain fewer than 100 counts. 
         [0096]    Evaluation of the atrioventricular histograms is performed by the atrioventricular interval timing analysis unit as follows: 
         [0097]    First, a distribution size is determined for each histogram. The distribution size is the sum of the counts in the bins from the second bin to the 26th bin, and thus excluding the shortest bin (&lt;102 ms). 
         [0098]    Preferably only those histograms are considered for further evaluation that have a distribution size of at least a quarter of the size of the histogram having the largest distribution size. 
         [0099]    Then, for each histogram a median atrioventricular interval is determined. The median atrioventricular interval is the upper boundary of the interval-bin that includes the median atrioventricular interval. The median atrioventricular interval is determined by calculating the cumulative distribution from the atrioventricular conduction histogram. The median atrioventricular interval is equivalent to the upper boundary of the interval-bin for which the cumulative sum first exceeds half of the total distribution size. 
         [0100]    In a similar manner, the atrioventricular interval timing analysis unit determines an upper limit for the atrioventricular conduction time. The upper limit atrioventricular interval is equivalent to the upper boundary of the interval-bin for which the cumulative sum first exceeds an upper-limit threshold. The count representing the upper-limit threshold is a specified fraction of the total counts, for example 97% of the total counts in the distribution. 
         [0101]    The atrioventricular interval timing analysis unit further determines an atrial sense latency time. The atrial sense latency time is the difference in appropriate measures of the ApVs and AsVs distributions for a given heart rate frequency band. The appropriate measures include the median atrioventricular interval and the upper limit atrioventricular interval. The upper limit atrioventricular interval is used to calculate the atrial sense latency time because it is least distorted by rhythm artifacts and is consistent with preserving a native atrioventricular conduction. 
         [0102]    Following the determination of the distribution size, the median atrioventricular interval, the upper limit atrioventricular interval and the atrial sense latency time, the atrioventricular interval timing analysis unit conducts an atrioventricular conduction analysis. The atrioventricular conduction analysis includes the determination of an upper ApVs conduction limit, an upper AsVs conduction limit, an average or median ApVs conduction interval, a average or median AsVs conduction interval, conduction dynamics for ApVs sequences, conduction dynamics for AsVs sequences and an average atrial latency time as follows: 
         [0103]    Upper ApVs Conduction Limit: 
         [0104]    The ApVs upper conduction limit is set to the longest of the upper-limit atrioventricular intervals obtained from the valid ApVs histogram distributions. 
         [0105]    Upper AsVs Conduction Limit: 
         [0106]    The AsVs upper conduction limit is set to the longest of the upper-limit atrioventricular intervals obtained from the valid AsVs histogram distributions. 
         [0107]    Average ApVs Conduction Interval: 
         [0108]    If two or more ApVs median intervals are available, the Significant Distributions are averaged. If a single ApVs median interval is available this ApVs median interval is used, otherwise, no measurement is made. 
         [0109]    Average AsVs Conduction Interval: 
         [0110]    If two or more AsVs median intervals are available, the Significant Distributions are averaged. If a single AsVs median interval is available AsVs median interval is used, otherwise, no measurement was made. 
         [0111]    Conduction Dynamics for ApVs Sequences 
         [0112]    If upper limit intervals are available for two or more ApVs rate bands, the conduction dynamics are calculated as the average conduction time difference per one positive step in the rate-band. The measured ApVs conduction dynamics is expressed in units milliseconds per beat per minute [ms/bpm]. The results are constrained to the range: −1.5 to 0.0 ms/bpm. 
         [0113]    Conduction Dynamics for AsVs Sequences 
         [0114]    If upper limit intervals are available for two or more AsVs rate bands; the conduction dynamics are calculated as the average conduction time difference per one positive step in the rate-band. The measured AsVs conduction dynamics is expressed in units of ms/bpm. The results are constrained to the range: −1.5 to 0.0 ms/bpm. 
         [0115]    Average Atrial Latency Time 
         [0116]    Average atrial latency time is determined for each heart rate band for which both the atrial-paced and atrial-sensed distributions are available. Atrial sense latency times are calculated as the ApVs upper-limit interval minus the AsVs upper-limit interval. Negative results are constrained to zero. The confidence in the latency measurement is based on the product of the number of counts in the paired distributions (ApVs counts*AsVs counts=confidence-product). The latency times having a confidence-product at least a quarter of the maximum confidence-product are averaged. The use of a quality measure with the latency measurements prevents infrequent timing events from distorting the average. 
         [0117]    For automatic atrioventricular timing analysis the atrioventricular interval timing analyzing unit is adapted to perform a method that includes the following steps:
       Accumulate and analyze atrioventricular intervals recorded over at least 24-hr, thereby using a long AV delay of 250 ms to 300 ms for ventricular stimulation.   Check for evidence of native (natural) atrioventricular conduction leading to intrinsic ventricular events Vs.
           If no evidence of native AV conduction are found, in particular if less than 3% of all recorded ventricular events are intrinsic ventricular events, then program standard AV delay values into the AV delay memory and do not enable AV hysteresis   If sufficient evidence of native AV conduction are found, in particular if equal to or more than 3% of all recorded ventricular events are intrinsic ventricular events, then
               determine a longer edge of the distribution of recorded atrioventricular intervals, e.g. the atrioventricular that forms the 97-th percentile of the recorded atrioventricular intervals,   calculate the atrial latency time   program the hysteresis AV delay to include the longer edge of the distribution of recorded atrioventricular intervals, e.g. the 97-th percentile interval,   program a short ApVp delay as follows:
                   preserve the AV hysteresis timing as constrained by the device&#39;s AV hysteresis options   target the short AV delay to be at least 30 ms shorter than the median ApVs interval   constrain the AV delay to be no shorter than 150 ms at &lt;70 ppm   
                   
               
               
 
         [0129]    The 97 th  percentile atrioventricular interval is determined in the same manner as the median atrioventricular interval or the upper limit atrioventricular interval: The 97 th  percentile atrioventricular interval is determined to be the atrioventricular interval that is assigned to the interval bin, which includes the atrioventricular interval sample for which at least 3% of all atrioventricular samples are longer. The 97 th  percentile atrioventricular interval is determined by summing the counts from the longest interval towards the shortest interval bin. The atrioventricular interval sample associated with the addition operation, which first causes the sum to exceed 3% of the total number of counts (the distribution size) is designated the upper limit atrioventricular interval. 
         [0130]    Parameter Selection for Atrioventricular Timing: 
         [0131]    With respect to programming an adequate AV delay and an adequate hysteresis AV delay for AV-sequential stimulation (atrium synchronous stimulation), the control unit and the memory of the heart stimulator are adapted as follows: 
         [0132]    If no automatic setting is available: 
         [0133]    If insufficient AV native AV conduction is observed, then standard AV timing parameters are used for AV delay. The latency compensation is programmed to the standard value. AV hysteresis is programmed “Off”. 
         [0134]    Otherwise, if sufficient native atrioventricular conduction is observed and thus sufficient atrioventricular interval data was recorded, automatic timing parameter adjustment is performed by the control unit and the atrioventricular interval timing analyzing unit: 
         [0135]    Automatic Latency Compensation 
         [0136]    The latency compensation is a negative valued programmable parameter. The corrected atrial latency should remain positive, and not be over corrected. The most negative value for latency compensation shall be selected, which obeys the following relationship: 
         [0000]      atrial latency+latency compensation≧zero 
         [0137]    Contingencies for automatic latency compensation are:
       If the atrial latency is invalid, then the latency compensation is programmed to the standard value.   If the atrial latency is zero or negative, then the latency compensation is programmed to Off.       
 
         [0140]    Automatic AV Hysteresis (Long ApVp Delay) 
         [0141]    Preference is given to permitting native AV sequential stimulation. The hysteresis AV delay is selected which is greater or equal to the longest upper limit atrioventricular interval for the significant distributions: 
         [0000]      Hysteresis AV delay≧upper ApVs conduction limit 
         [0000]      and 
         [0000]      Hysteresis  AV  delay≧(upper  AsVs  conduction limit−latency compensation) 
       Automatic AV Delay (Short ApVp Delay) 
       [0142]    The ApVp delay is selected to approach the optimal hemodynamic performance for pacing therapy. If the patient&#39;s optimal ApVp interval has been independently determined, it shall provide the preferred targeted ApVp interval. In the absence of a patient specific optimal ApVp interval, the targeted ApVp interval is estimated based on the median ApVs interval minus 30 ms. Since the putative ApVp interval may be biased by the clinical condition of the patient, the programmed value is constrained by the lower limit of the published range for optimal ApVp intervals: 160±20 ms. The constrained ApVp interval is the targeted ApVp delay. 
       Contingency for Automatic AV Delay: 
       [0143]    If the targeted ApVp delay cannot be programmed due to limited programming options, the nearest available ApVp delay shall be used. 
         [0144]    Although an exemplary embodiment of the present invention has been shown and described, it should be apparent to those of ordinary skill that a number of changes and modifications to the invention may be made without departing from the spirit and scope of the invention. For example, the principles of atrioventricular interval analysis and the principles of automatic or device-assisted semi-automatic AV-delay adjustment can be applied to dual or more chamber heart stimulators including ICDs. Furthermore, all features illustrated above can be integrated into an implantable medical device itself. However, it is also possible to have only parts of the heart stimulation system that are needed for daily operation of the implant are integrated in the implant while other parts such as the atrioventricular interval timing analyzing unit can be implemented into an external device that is remotely connected to the implant. This invention can readily be adapted to such devices by following the present teachings. All such changes, modifications and alterations should therefore be recognized as falling within the scope of the present invention.