Abstract:
A device is connected to electrode leads which performs intracardiac impedance measurements, conducts a transient pacing protocol, analyses the impedance measurements, and generates an LV lead position quality factor. The transient pacing protocol includes a repeated change (“transitions”) between ventricular intrinsic rhythm and biventricular paced rhythm and may also include a variation of the atrioventricular delay (AVD) and/or the interventricular delay (VVD). The quality factor expresses the degree to which hemodynamic properties have improved due to BiV stimulation for the current LV lead position compared to intrinsic ventricular rhythm.

Description:
FIELD OF INVENTION 
       [0001]    The invention refers to implantable medical devices (IMDs) providing improved means for pacing efficiency. The invention relates in particular to an implantable cardiac pacemaker or an implantable cardioverter/defibrillator (ICD) for bi-ventricular stimulation, and to methods for optimizing a left ventricular electrode lead site. 
       BACKGROUND OF THE INVENTION 
       [0002]    For patients suffering from congestive heart failure (CHF), the synchronized stimulation of the atrium and both the right and left ventricle by an implantable pacemaker or defibrillator, called cardiac resynchronization therapy (CRT), has been shown to improve the prognosis. 
         [0003]    For biventricular (BiV) pacing (stimulation of both ventricles of a heart), both right ventricular (RV) and left ventricular (LV) stimulation electrode leads bearing right ventricular and left ventricular stimulation electrodes are used. The LV electrode lead is implanted via the right atrium and coronary sinus into a LV cardiac vein. Often, several positions are available for the implantation site of the LV electrode lead. In order to be beneficial, the final position of the LV stimulation electrode should be optimized for hemodynamic benefit. 
         [0004]    Pacing of the right atrium (RA), right ventricle (RV), and the left ventricle (LV) is performed by delivery of stimulation pulses to the respective heart chamber. The stimulation pulses have strength strong enough to be captured by the respective heart chamber and cause an excitation of the heart chamber&#39;s myocardium. Causing an excitation of a heart chamber that leads to contraction of said heart chamber by means of an electric stimulation pulse is called pacing the heart chamber. 
         [0005]    Thus stimulated contractions of a heart chamber, called “pace events,” and natural contractions of a heart chamber, called “intrinsic events,” may occur. In a healthy heart, the natural rhythm or rate of intrinsic events is controlled by the sinus node of the heart. Therefore, the natural rhythm of intrinsic events is called “sinus rhythm” or “sinus rate”. 
         [0006]    The pacing site of the left ventricular lead for cardiac resynchronization therapy can be optimized by measuring hemodynamic parameters, which increases duration, complexity and costs of the implantation procedure. 
         [0007]    Established methods for assessing the efficiency of biventricular pacing are listed in the following. The following methods can be used to optimize the LV lead implant position and also the pacing timing parameters: 
         [0008]    a) noninvasive methods or those using the implanted electrodes:
       optimize electrical synchrony (ECG)   maximum delay between RV IEGM and LV IEGM during ventricular intrinsic rhythm   maximum plethysmographic pulse pressure during BiV stimulation   maximum SV (Echo, Doppler echo) during BiV stimulation   minimize mitral regurgitation (mitral insufficiency backflow doppler VTI)   optimize mechanical synchrony (tissue doppler)   implanted sensors (peak endocardial acceleration, RV pressure)       
 
         [0016]    b) invasive measurements:
       maximum arterial pulse pressure during BiV stimulation   maximum dp/dtmax of LV pressure during BiV stimulation   minimum LV EDP, LAP, PCWP during BiV stimulation   maximum SV (thermodilution, pulse contour analysis) during BiV stimulation
           optimize electrical synchrony (IEGM mapping)   
               
 
         [0022]    The methods that reliably assess hemodynamic parameters considerably increase the effort required during implantation, since either additional equipment is needed (e.g. Echo) or invasive measurements are required (e.g. intracardiac catheter). 
       SUMMARY OF THE INVENTION 
       [0023]    It is an object of the invention to provide an implantable medical device that provides an improved assessment of the efficiency of biventricular (BiV) pacing. 
         [0024]    According to the invention, the efficiency of biventricular pacing is expressed by a quality factor. 
         [0025]    The quality factor can be used to optimize an electrode lead position, in particular a left ventricular (LV) electrode position, or bi-ventricular pacing parameters such as an interventricular delay (VVD) or an atrioventricular delay (AVD), or both. The concept of scheduling stimulation pulses based on the delays mentioned is deemed to be general knowledge of the person skilled in the art. The same applies to the concept of demand pacing etc. 
         [0026]    According to the present invention the object of the invention may be achieved by a heart stimulator for biventricular pacing of a heart, featuring:
       at least one stimulation pulse generator for pacing at least a left ventricle of a heart,   an impedance determination unit for determining an intracardiac impedance value reflecting cardiac output,   and a control unit, being connected to said stimulation pulse generator and to said impedance determination unit.       
 
         [0030]    The control unit is adapted to trigger said stimulation pulse generator to generate and deliver at least left ventricular stimulation pulses when triggered and to perform a quality factor test procedure for determining a quality factor. The control unit is further adapted to determine the quality factor by comparing two impedance values. 
         [0031]    A first intracardiac impedance value is determined for an intrinsic heart cycles sequence comprising a predetermined first number N intrinsic  of consecutive intrinsic heart cycles wherein no left ventricular stimulation pulses are delivered. A second intracardiac impedance value is determined for a paced heart cycles sequence comprising a predetermined second number N paced  of consecutive paced heart cycles wherein at least left ventricular stimulation pulses are delivered. 
         [0032]    The invention is based on the idea that intracardiac impedance (Z) reflects left ventricular (LV) volume changes well and it therefore can be used as an alternative method to guide LV electrode lead positioning. 
         [0033]    According to the invention, the hemodynamically best implantation site for the LV lead is identified by intracardiac impedance measurements using the LV lead itself and (possibly) other already implanted leads (RV lead, RA lead) and (possibly) a patch electrode. No other invasive parts are required than the device electrodes, which are implanted anyway. 
         [0034]    For that purpose, a device (e.g., the control unit) is provided which connects to the electrode leads and—while performing the quality factor test procedure—performs intracardiac impedance measurements, conducts a certain stimulation protocol (called “transient pacing protocol”), analyzes the impedance measurements, and generates an LV lead position quality factor. 
         [0035]    The transient pacing protocol includes a repeated change (“transitions”) between ventricular intrinsic rhythm and biventricular paced rhythm and may also include a variation of the atrioventricular delay (AVD) and/or the interventricular delay (VVD). 
         [0036]    The quality factor expresses the degree to which the hemodynamic properties have improved due to BiV stimulation for the current LV lead position compared to intrinsic ventricular rhythm. If the quality factor is determined as being the quotient of the first and the second intracardiac impedance value, a quality factor of (for example) 1.2 means that hemodynamic properties have improved by 20% over the intrinsic rhythm by BiV pacing; a quality factor &lt;1.0 would mean that BiV pacing is hemodynamically worse than intrinsic rhythm. 
         [0037]    Accordingly, in a preferred embodiment, the control unit is adapted to compare the first and the second impedance value by dividing the second impedance value by the first impedance value, the quotient being said quality factor. 
         [0038]    During transient pacing, preferably impedance curves (Z-curves) are recorded. 
         [0039]    Preferably, the control unit is adapted to calculate at least some of the parameters needed for calculation of the quality factor from the following list of parameters for both the intrinsic and the BiV pacing impedance curves of each intrinsic-BiVpacing transition, preferably using the mean or median impedance Z mean : 
         [0040]    EDZ: end diastolic impedance (minimum impedance in diastolic time window, may be approximated by the minimum impedance or even by Z mean ) 
         [0041]    ESZ: end systolic impedance (maximum impedance in systolic time window, may be approximated by the maximum impedance) 
         [0042]    SZ: ESZ-EDZ (may be approximated by the impedance amplitude or standard deviation, the maximum or minimum or maximum absolute impedance slope, or another quantity characterizing the impedance variation width) 
         [0043]    EF: ejection fraction-like parameter, EF =SZ/ESZ, or approximated by EF =SZ mean    
         [0044]    These parameter values are used to determine the quality factors by calculating the ratio (quotient) of these parameter values during both rhythms. 
         [0045]    Details of determination of these parameters can be found in US 2005/0049646 and are incorporated herein by reference. 
         [0046]    It is further preferred that the control unit calculates the quality factor by one of the following methods: 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
               
                   
                 quality factor calculation 
                 interpretation 
               
               
                   
                   
               
             
             
               
                   
                 ESZ_BiV/ESZ_intr* 
                 relative ESV reduction 
               
               
                   
                 EDZ_intr/EDZ_BiV* 
                 relative EDV increase 
               
               
                   
                 SZ_BiV/SZ_intr 
                 relative SV increase 
               
               
                   
                 EF_BiV/EF_intr 
                 relative EF increase 
               
               
                   
                   
               
               
                   
                 *Impedance Z is expected to be inversely proportional to LV volume 
               
             
          
         
       
     
         [0047]    Alternatively the corresponding quantities may be calculated using the conductivity Y=1/Z (taking care that in the quality factors described in the first two lines of the table, the numerator and denominator change places, and EF=SY/EDY or SY/Y mean ). 
         [0048]    The quality factor is preferably calculated separately for each intrinsic-BiVpacing transition (or each group of intrinsic-BiVpacing transitions), resulting in N averages  values for the quality factor. The quality factors from all transition groups may then be averaged to form the one resulting quality factor for the current LV lead position (and the current AVD and VVD values). 
         [0049]    Alternatively, the parameter values may be first averaged over all intrinsic-BiVpacing transitions, and then the quality factors may be calculated from the averaged parameters for intrinsic and for BiVpaced rhythm. This approach needs less computing power, since only one division is required for the quality factor calculation. 
         [0050]    This device may be a stand-alone external device, or an electrophysiological tester with an integrated module performing the described tasks, or an implant programmer with an integrated part performing the described tasks, or the implant itself may perform these tasks in cooperation with the implant programmer. 
         [0051]    Furthermore, the implant may perform this measurement independently and automatically with a programmable periodicity to check whether the LV lead position quality factor has changed, and to generate a “LV lead displacement” warning if the factor deteriorates significantly, and send the warning to a remote home monitoring service center, or warn the patient audibly. 
         [0052]    Preferably, the intrinsic heart cycles sequence and the paced heart cycles sequence are repeated in an alternating manner for predetermined number N transitions  of sequences. 
         [0053]    It is further preferred that the first number N intrinsic  of consecutive intrinsic heart cycles is larger, e.g. 2 to 5 times larger, than said second number N paced  of consecutive paced heart cycles. 
         [0054]    A preferred value for the first number N intrinsic  of consecutive intrinsic heart cycles is around 15 and a preferred value for the second number N paced  of consecutive intrinsic heart cycles is in the order of 5. 
         [0055]    Preferably, the control unit is adapted to trigger both ventricles of a heart in each sequence of consecutive paced heart cycles. 
         [0056]    The stimulation pulse generator is preferably connected to a coronary sinus pacing lead being adapted to be placed in the coronary sinus of a heart and bearing a left ventricular stimulation electrode at its distal end or close to its distal end. In this preferred embodiment, it is the position of the coronary sinus lead that is to be optimized. 
         [0057]    After implantation of the RV and possibly the RA lead, the LV electrode is placed in the first position under consideration, the pacing and sensing thresholds of the implanted leads are determined and an impedance measurement sequence is started by the external device, which calculates and displays a quality factor for that position. 
         [0058]    The physician may then decide that this position is suitable if the quality factor is sufficiently above 1.0, indicating a hemodynamic improvement over the intrinsic rhythm. 
         [0059]    The physician may also move the LV lead to other possibly suitable positions and repeat the measurement for these positions. The position with the highest quality factor is considered as the hemodynamically best site and should be used for the final implant position of the LV lead. The external device may also provide a preferred AVD and/or VVD for that site. 
         [0060]    With respect to impedance measurement, it is preferred that the impedance determination unit is connected to or connectable to two separate electrodes of a right ventricular pacing lead for current injection and to two separate electrodes of a left ventricular pacing lead for voltage measurement. 
         [0061]    The impedance measurement is performed by injecting a current using two electrodes and measuring the induced voltage between two (possibly different) electrodes. The electrodes that may be chosen for the impedance measurement include the intracardiac electrodes (RA tip and ring, RV tip and coil or ring, LV distal and proximal, LA distal and proximal), the intrathoracic electrode (vena cava electrode, implant housing) and possibly additional patch electrodes attached to the patient. 
         [0062]    The impedance preferably is measured by injecting a pulsed biphasic current and measuring the induced voltage phase synchronous. Preferably the impedance determination unit is adapted to sample the induced voltage at a rate of at least 8 Hz over a complete heart cycle or only within a systolic and a diastolic time window, determined relative to the heart timing from intracardiac electrogram (IEGM). 
         [0063]    Preferably the current is injected between a right ventricular (RV) tip and coil (or ring) electrode and the voltage is measured between LV distal and proximal electrodes. 
         [0064]    Details and variations of impedance measurement can be taken from U.S. Patent Application 2005/0049646, which is incorporated herein by reference. 
         [0065]    During the impedance measurement in the course of the quality factor test procedure the control unit performs the transient pacing protocol, causing the control unit to switch several times between intrinsic ventricular rhythm and biventricular paced rhythm. 
         [0066]    The number of consecutive paced cycles, N paced , is preferably smaller than about 10 cycles (see below). 
         [0067]    The number of consecutive cycles in intrinsic rhythm, N intrinsic , is larger than the number of consecutive cycles in BiV paced rhythm, N paced , preferably by a factor of 2 to 5. (For example, when N paced =5, N intrinsic =15, a transient protocol proceeds with: 5 cycles paced—15 cycles intrinsic—5 cycles paced—15 cycles intrinsic— . . . ). 
         [0068]    The number of transient repetitions, N transitions  (i.e. how often the rhythm changes from intrinsic to BiV stimulation) needs to be large enough that the total number of BiV paced cycles is sufficient to cover several respiration cycles (in order to be able to remove the effect of respiration on the impedance curve by averaging), preferably 4-16 repetitions. 
         [0069]    The reason for this protocol is threefold:
       1. The impedance curves for BiV pacing and intrinsic rhythm can be compared for the same LV lead position. The absolute impedance value (EDZ) and the amount of change during the heart cycle (SZ) measured is strongly dependent on the electrode position due to electrical reasons, rather than hemodynamic reasons. For that reason, it makes no sense to compare EDZ or SZ between different sites. However, the relative change of these quantities between intrinsic rhythm and BiV stimulation is expected to depend on the hemodynamic benefit due to BiV pacing at this position.   2. The hemodynamic condition of the patient changes with time, therefore a quick repeated switching between intrinsic (as a reference) and BiV paced rhythm allows to separate the (comparatively slow) changes in reference hemodynamic condition from the (immediate) effect of switching to BiV pacing. Otherwise, a change of the hemodynamic condition, which incidentally may occur just upon changing to the next lead position, could lead to incorrect conclusions.   3. Upon change to BiV pacing from intrinsic rhythm, the autonomic nervous system automatically compensates for the changed hemodynamic pumping efficiency by modulating contractility, total peripheral resistance and (if in intrinsic rhythm) atrial rate. This compensation may mask the change of pumping efficiency. Since some compensation mechanisms react within a few heart cycles, the BiV pacing sequences should be shorter than about 10 cycles.       
 
         [0073]    The control unit may further be adapted to use either the heart&#39;s own intrinsic rhythm (sinus rhythm) throughout the transient pacing protocol (the right atrium is not paced by setting the basic rate of the pacemaker below the sinus rate), or, preferably, to stimulate the atrium throughout the transient protocol at a constant rate sufficiently (5-30 ppm) above the sinus rate in order to prevent a take-over by the intrinsic rhythm. 
         [0074]    Further, the control unit can be adapted to hold an atrioventricular delay (AVD) constant while performing the transient protocol. Preferably, the AVD is sufficiently shorter than the intrinsic atrioventricular (AV) conduction time, preferably 60% of intrinsic AV conduction time. 
         [0075]    Similarly, the control unit can be adapted to hold an interventricular delay (VVD) constant during performing the transient protocol, preferably at about 0 ms. 
         [0076]    As pointed out above, in preferred embodiment, the control unit may be adapted to implicitly optimize the atrioventricular delay AVD and/or the interventricular delay VVD for bi-ventricular pacing. 
         [0077]    To achieve such implicit AVD and/or VVD optimization, the control unit is preferably adapted to perform the described transient pacing protocol at each LV lead site several times for a set of atrioventricular delays (all shorter than intrinsic conduction) and take the best quality factor found as quality factor for that position. Since this represents an implicit AVD optimization for each test-site, the AVD values corresponding to the best quality factor can be stored in memory for each LV lead position (in order to be suggested for programming the AVD after final lead positioning). 
         [0078]    Similarly, the control unit may be adapted to perform the described transient pacing protocol at each LV lead site several times for a set of interventricular delays (VVDs) and take the best quality factor found as quality factor for that position. Since this represents an implicit VVD optimization for each test-site, the VVD values corresponding to the best quality factor can be stored in memory for each LV lead position (in order to be suggested for programming the VVD after final lead positioning). 
         [0079]    Both AVD and VVD variation may by combined by first varying the AVD, then using the AVD with the best quality factor and performing the pacing protocol again with variation of the VVD. 
         [0080]    With respect to impedance analysis, it is preferred that the control unit is adapted to calculate two averaged impedance curves (Z-curves) for each intrinsic to BiV paced transition:
       one from the N paced  cyles of the BiV paced rhythm after the transition, and   one from the N reference  intrinsic cycles immediately before the transition       
 
         [0000]      N reference =N paced    
         [0083]    Thus, a number of (N intrinsic −N reference ) intrinsic cycles following the BiV paced cycles are discarded. As an example, N paced =5, N intrinsic =15, N reference =5 (i.e., 10 intrinsic cycles are not included in the analysis). 
         [0084]    For calculating averaged impedance curves, the ventricular event from the IEGM or pacemaker timing is used for synchronization. 
         [0085]    This results in N averages =N transitions  pairs of averaged impedance curves. Alternatively also N group =2 or 4 subsequent transitions may be grouped for the calculation of averaged impedance curves (resulting in N averages =N transitions /2 or N transitions /4 pairs of averaged impedance curves). 
         [0086]    Additionally the resulting averaged curves may be processed using the following methods:
       smoothing   removal of known technically caused artefacts   removal of artefacts caused by the ventricular IEGM   curve fitting       
 
         [0091]    The preprocessed Z-curves are analyzed and one or several parameters are extracted that characterize certain attributes of the impedance curve (separately for the N averages  BiVpaced curves and intrinsic curves). 
         [0092]    It is to be appreciated that features of preferred embodiments of the invention may be combined in any useful manner thus arriving at further embodiments of the invention not explicitly mentioned in this disclosure. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0093]    The foregoing 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: 
           [0094]      FIG. 1  shows a dual chamber pacemaker/atrial defibrillator/cardioverter connected to electrode leads placed in a heart. 
           [0095]      FIG. 2  is a schematic block diagram of the heart stimulator of  FIG. 1 . 
           [0096]      FIG. 3  is a schematic overview of the impedance analysis from the heart cycles to the quality factor for one LV lead position without AVD or VVD variation (for Nintrinsic=15, Nreference=5, Npaced=5, Ntransitions=8, Ngroup=2, Naverages=4, extracted parameter=SZ) and 
           [0097]      FIG. 4  is a flow chart illustrating the quality factor determination by the heart stimulator of  FIG. 2 . 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0098]    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. 
       DESCRIPTION OF THE PREFERRED EMBODIMENT 
       [0099]    From  FIG. 1  it is apparent that stimulator  10  comprises a case  12  and header  14 . 
         [0100]    The heart stimulator  10  is connected to three electrode leads, namely a right ventricular electrode lead  16 , a right atrial electrode lead  18  and a left ventricular electrode lead  20 . The left ventricular electrode lead  20  is designed to pass through the coronary sinus of heart  22 . A typical electrode suitable for use with heart stimulator  10  is the electrode lead corox+UP/BB (Biotronik). 
         [0101]    Left ventricular electrode lead  20  comprises a left ventricular tip electrode  24  at the distal end of the left ventricular electrode lead  20  and a left ventricular ring electrode  26 . 
         [0102]    Atrial electrode lead  18  comprises a right atrial tip electrode  28  at the distal end of the right atrial electrode lead  18  and a right atrial ring electrode  30 . 
         [0103]    The right ventricular electrode lead  16  comprises right ventricular tip electrode  32  at the distal end of the right ventricular electrode lead  16  and a right ventricular ring electrode  34 . 
         [0104]    In order to illustrate that heart stimulator  10  may be adapted to act as an implantable cardioverter/defibrillator (ICD) ventricular electrode lead  16  also includes a ventricular shock coil  36  for the delivery of defibrillation shocks to the right ventricle  38  of the heart  22  and an atrial shock coil  40  for the delivery of atrial defibrillation shocks to a right atrium  42  of the heart  22 . 
         [0105]    Each electrode and shock coil of electrode leads  16  to  20  is separately connected to an electric circuit enclosed by case  12  of heart stimulator  10  by way of electrical contacts of a plaque (not shown) at the proximal end of each electrode lead  16  to  20  and corresponding contacts (not shown) in header  14  of heart stimulator  10 . 
         [0106]    Right atrial shock coil  40  is connected to right atrial shock generator  50  (see  FIG. 2 ) that is controlled by a control unit  52  of heart stimulator  10 . 
         [0107]    Similarly right ventricular shock coil  36  is connected to a right ventricular shock generator  54  that is also connected to control unit  52 . 
         [0108]    Right atrial tip electrode  28  and right atrial ring electrode  30  are both connected to right atrial stimulation pulse generator  56  and to a right atrial sensing stage  58  that are in turn connected to control unit  52 . 
         [0109]    Right atrial stimulation pulse generator  56  is adapted to generate atrial stimulation pulses of sufficient strength to cause an excitation of atrial myocardium by an electrical stimulation pulse delivered via right atrial tip electrode  28  and right atrial ring electrode  30 . Preferably, means are provided to adapt the right atrial stimulation pulse strength to the stimulation threshold. 
         [0110]    Right atrial sensing stage  58  is adapted to pick up myocard cardial potentials indicating an intrinsic atrial excitation that corresponds to a natural atrial contraction. By way of right atrial sensing stage  58 , it is possible to stimulate the right atrium  42  of heart  22  in a demand mode wherein a right atrial stimulation pulse is inhibited if an intrinsic atrial event (intrinsic atrial excitation) is sensed by right atrial sensing stage  58  prior to expiration of an atrial escape interval. 
         [0111]    In a similar manner, right ventricular ring electrode  34  and right ventricular tip electrode  32  are connected to a right ventricular stimulation pulse generator  60  and to a right ventricular sensing stage  62  that in turn are connected to control unit  52 . By way of right ventricular tip electrode  32 , right ventricular ring electrode  34 , right ventricular stimulation generator  60  and right ventricular sensing stage  62 , right ventricular stimulation pulses can be delivered in a demand mode to the right ventricle  38  of heart  22 . 
         [0112]    In the same way left ventricular tip electrode  32  and left ventricular ring electrode  26  are connected to the left ventricular stimulation pulse generator  64  and the left ventricular sensing stage  66  that are in turn connected to control unit  52  to allow for stimulation of a left ventricle  70  of heart  22 . 
         [0113]    Triggering and inhibition of delivery of stimulation pulses to the right atrium, the right ventricle or the left ventricle is controlled by control unit  52 , in a manner known to the skilled artisan. The timing that schedules delivery of stimulation pulses if needed is controlled by a number of intervals which may at least partly depend on a hemodynamic demand of a patient that is sensed by means of an activity sensor  72  connected to control unit  52 . Activity sensor  72  allows for rate adaptive pacing wherein a pacing rate (the rate of consecutive ventricular stimulation pulses for a duration of consecutive atrial stimulation pulses) depends on a physiological demand of a patient that is sensed by the activity sensor  72 . Details of rate adaptation are known to the skilled artisan and need not to be explained in detail in this description. 
         [0114]    Whereas an actual stimulation rate determines the timing from one (paced) heart cycle to another, intervals like an atrioventricular delay interval and an interventricular delay interval determine the timing within one heart cycle. Starting with an atrial event, the right ventricle would be excited (either intrinsically or paced) at the end of an atrioventricular delay interval. A left ventricular contraction should follow the right ventricular contraction at the end of an interventricular delay interval. This includes the case wherein the right ventricle and the left ventricle are excited at the same time, resulting in an interventricular delay interval duration of zero. Also, it is possible that the left ventricle may be excited prior to the right ventricle resulting in an negative interventricular delay interval duration. 
         [0115]    In any case, the atrioventricular delay interval duration and the interventricular delay interval duration need to be adapted to an individual heart in order to achieve an optimized cardiac output. 
         [0116]    Heart stimulator  10  is adapted to determine an optimal atrioventricular delay interval duration and an optimal interventricular delay interval duration automatically. 
         [0117]    For this purpose, heart stimulator  10  includes an impedance determination unit  74  that includes a constant current source  76  and a voltage measuring unit  78 . The constant current source  74  generates a pulsed biphasic current that comprises pairs of current pulses that have an alternating polarity and the same absolute current strength. An impedance determination stage  80  calculates an impedance value based on the current strength and the voltage measured. As will be appreciated by the skilled artisan, instead of measuring the impedance, the inverse value of the impedance, equivalent values such as male conductivity or conductance, respectively, can be used throughout the invention in an analogous manner taking into account the inverse relationship. 
         [0118]    Control unit  40  is adapted to determine a quality factor that represents the efficiency of biventricular pacing. In order to determine the quality factor, impedance measurements are performed while applying a transient pacing protocol controlled by the control unit  40 . 
         [0119]    The transient pacing protocol causes the control unit to switch several times between intrinsic ventricular rhythm (no triggering of stimulation pulses for a number of N intrinsic  heart cycles) and biventricular paced rhythm. 
         [0120]    The number of consecutive paced cycles, N paced , is preferably smaller than 10 cycles (see below). 
         [0121]    The number of consecutive cycles in intrinsic rhythm, N intrinsic , is larger than the number of consecutive cycles in BiV paced rhythm, N paced , preferably by a factor of 2 to 5. (For example, where N paced =5, N intrinsic =15, a transient protocol may take the form: 5 cycles paced—15 cycles intrinsic—5 cycles paced—15 cycles intrinsic— . . . ). 
         [0122]    The number of transient repetitions, N transition , (i.e. how often the rhythm changes from intrinsic to BiV stimulation) needs to be large enough that the total number of BiV paced cycles is sufficient to cover several respiration cycles (in order to be able to remove the effect of respiration on the impedance curve by averaging), preferably 4 to 16 repetitions. 
         [0123]    To achieve an implicit AVD and/or VVD optimization, the control unit is adapted to perform the described transient pacing protocol at each LV lead site several times for a set of atrioventricular delays (all shorter than intrinsic conduction) and take the best quality factor found as quality factor for that position. Since this represents an implicit AVD-optimization for each test-site, the AVD values corresponding to the best quality factor can be memorized for each LV lead position so that they may be used for programming the AVD after final lead positioning. 
         [0124]    Similarly, the control unit is adapted to perform the described transient pacing protocol at each LV lead site several times for a set of interventricular delays (VVD&#39;s) and take the best quality factor found as quality factor for that position. Since this represents an implicit VVD optimization for each test-site, the VVD values corresponding to the best quality factor can be memorized for each LV lead position so that they may be used for programming the VVD after final lead positioning. 
         [0125]    Both AVD and VVD variation are combined by first varying the AVD, then using the AVD with the best quality factor and performing the pacing protocol again with variation of the VVD. 
         [0126]    Alternatively, in a more simple embodiment, both the atrioventricular delay (AVD) and the interventricular delay (VVD) can be held constant. Then, the atrioventricular delay (AVD) is sufficiently shorter than the intrinsic atrioventricular (AV) conduction time, preferably about 60% of intrinsic AV conduction time. The interventricular delay (VVD) preferably is about 0 ms. 
         [0127]    During performing the the transient pacing protocol either sinus rhythm is used throughout (the right atrium is not paced by setting the basic rate of the pacemaker below the sinus rate), or, preferably, the atrium is stimulated throughout the transient protocol at a constant rate (5-30 ppm) sufficiently above the sinus rate in order to prevent a take-over by the intrinsic rhythm. 
         [0128]    For each intrinsic to BiV paced transition, two averaged impedance curves are calculated:
       one from the N paced  cyles of the BiV paced rhythm after the transition, and   one from the N reference  intrinsic cycles immediately before the transition       
 
         [0000]      N reference =N paced    
         [0131]    Thus, a number of (N intrinsic −N reference ) intrinsic cycles following the BiV paced cycles are discarded. As a preferred example, N paced =5, N intrinsic =15, N reference =5 (i.e., 10 intrinsic cycles are not included in the analysis). 
         [0132]    The control is further adapted to calculate averaged impedance curves (Z-curves) while performing the transient pacing protocol as follows: 
         [0133]    For calculating averaged impedance curves, the ventricular event from the IEGM or pacemaker timing is used for synchronization. 
         [0134]    This results in N averages =N transitions  pairs of averaged impedance curves. Alternatively also N group =2 or 4 subsequent transitions may be grouped for the calculation of averaged impedance curves (resulting in N averages =N transitions /2 or N transitions /4 pairs of averaged impedance curves). 
         [0135]    Additionally the resulting averaged curves may be processed using the following methods:
       smoothing   removal of known technically caused artifacts   removal of artifacts caused by the ventricular IEGM   curve fitting       
 
         [0140]    The preprocessed Z-curves are analyzed and one or several parameters are extracted, that characterize certain attributes of the impedance curve (separately for the Naverages BiVpaced curves and intrinsic curves). 
         [0141]    Preferably a subset (that is needed for calculation of the quality factor) from the following list of parameters is calculated for both the intrinsic and the BiV impedance curves of each intrinsic-BiV pacing transition: 
         [0142]    Z mean : the mean or median impedance 
         [0143]    EDZ: end diastolic impedance (minimum impedance in diastolic time window, may also be approximated by the minimum impedance or even by Z mean ) 
         [0144]    ESZ: end systolic impedance (maximum impedance in systolic time window, may also be approximated by the maximum impedance) 
         [0145]    SZ: ESZ-EDZ (may also be approximated by the impedance amplitude or standard deviation, the maximum or minimum or maximum absolute impedance slope, or another quantity characterizing the impedance variation width) 
         [0146]    EF: ejection fraction-like parameter, EF=SZ/ESZ, or approximated by EF=SZ/Z mean    
         [0147]    These parameter values are used by the control unit to determine the quality factors by calculating the ratio (quotient) of these parameter values during both rhythms. 
         [0148]    Preferably the quality factor is calculated by one of the following methods: 
         [0000]    
       
         
               
               
               
             
           
               
                   
                   
               
               
                   
                 quality factor calculation 
                 interpretation 
               
               
                   
                   
               
             
             
               
                   
                 ESZ_BiV/ESZ_intr* 
                 relative ESV reduction 
               
               
                   
                 EDZ_intr/EDZ_BiV* 
                 relative EDV increase 
               
               
                   
                 SZ_BiV/SZ_intr 
                 relative SV increase 
               
               
                   
                 EF_BiV/EF_intr 
                 relative EF increase 
               
               
                   
                   
               
               
                   
                 *Impedance Z is expected to be inversely proportional to LV volume 
               
             
          
         
       
     
         [0149]    Alternatively the corresponding quantities may be calculated using the conductivity Y=1/Z (taking care that in the quality factors described in the first two lines of the table numerator and denominator change places, and EF=SY/EDY or SY/Y mean ). 
         [0150]    The quality factor is now calculated separately for each intrinsic-BiVpacing transition (or each group of intrinsic-BiVpacing transitions), resulting in N averages  values for the quality factor. The quality factors from all transition groups are then averaged to form the one resulting quality factor for the current LV lead position (and the current AVD and VVD values). 
         [0151]    A schematic overview of the impedance analysis (for N intrinsic =15, N reference =5, N paced =5, N transitions =8, N group =2, N averages =4, extracted parameter=SZ) is shown in  FIG. 3 . 
         [0152]    Alternatively, the parameter values may be first averaged over all intrinsic-BiVpacing transitions, and then the quality factors may be calculated from the averaged parameters for intrinsic and for BiVpaced rhythm. This approach needs less computing power; since only one division is required for the quality factor calculation. 
         [0153]    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. In particular, it is possible to implement the features of the claimed transceiver unit into state of the art implantable medical devices such as implantable pacemakers or implantable cardioverter/defibrillator. 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.