Abstract:
An implantable cardiac stimulator includes at least one first sensing unit for detecting intrinsic cardiac activities of a first ventricle, at least one ventricular stimulation unit for stimulating a second ventricle, and a stimulation control unit connected to the first sensing unit. The stimulation unit processed output signals of the first sensing unit and generates control signals for the stimulation units. The stimulation control unit derives a current intrinsic RR interval from detected ventricular intrinsic cardiac activities R of the first ventricle, and to determine from the RR interval a delay interval Δ, which begins with a ventricular event of the first ventricle and at the end of which the stimulation control unit triggers a stimulation of the second ventricle (unless it is suppressed).

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims priority under 35 USC 119(e) to U.S. Provisional Patent Application 61/228,978 filed Jul. 28, 2009, the entirety of which is incorporated by reference herein. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention relates to an implantable cardiac stimulator (e.g., a cardiac pacemaker, an implantable cardioverter/defibrillator (ICD), or a combination of these devices), preferably one which is capable of stimulating both ventricles of the heart, for cardiac resynchronization therapy (CRT). 
       BACKGROUND OF THE INVENTION 
       [0003]    A cardiac stimulator of the aforementioned type typically has at least one right-ventricular sensing unit and one right-ventricular stimulation unit, plus one left-ventricular sensing unit and one left-ventricular stimulation unit. These units are connected by electrode lines to electrodes situated at suitable locations in the heart during operation of the cardiac stimulator. A left-ventricular electrode line typically bears the electrodes for detecting electric potentials in, and delivering stimulation pulses to, the left ventricle of the heart. The left-ventricular electrode line is usually implanted through the coronary sinus of the heart, and therefore is also referred to as a coronary sinus electrode line, though it may instead be an epicardial or endocardial electrode line to the left ventricle. The electrodes for detecting electric potentials in, and delivering stimulation pulses to, the right ventricle are typically attached to a right-ventricular electrode line whose distal end is situated at the apex of the right ventricle. The electrode lines are typically connected at their proximal end to a cardiac stimulator via standardized plug connections. 
         [0004]    Typical stimulation modes for a right-ventricular cardiac stimulator, e.g., VVI, VVD or DDD, are well-known. The same is also true regarding modes for delivery of stimulation pulses only in case of need (demand pacemaker modes), in which delivery of a stimulation pulse to a particular chamber of the heart is suppressed when an assigned sensing unit of the cardiac stimulator has detected an intrinsic pulse in the chamber during a corresponding escape interval. These known concepts may be implemented with the cardiac stimulator described here. 
         [0005]    Automatic (non-stimulated) contractions of a particular cardiac chamber are also referred to as intrinsic events, sense events, or intrinsic cardiac activities. They may be detected in a known manner by corresponding sensing units, which are connected to a particular electrode for detecting myocardial potentials during operation. In order for a particular sensing unit to avoid impairment by a potential due to the delivery of a stimulation pulse, sensing units are typically designed so that they do not detect any events within a short blanking period following a stimulus. Delivery of a stimulation pulse is also known as a pace event. 
         [0006]    In common cardiac resynchronization therapy methods, to correct a dys-synchronicity of the right and left ventricles, the ventricles are electrically stimulated in order to ensure a defined interventricular delay time (VV delay, or VVD). This is true even with intact AV conduction, i.e., with natural conduction of a stimulus triggering a contraction from the atrium to the ventricle over the AV node. This methodology foregoes a more efficient contraction of the intrinsically stimulable ventricle and the associated natural regulation of AV delay (which also reflects physical exertion, for example). 
         [0007]    US Published Patent Appln. 2009/0125077 proposes a cardiac stimulator which can automatically switch between a plain right-ventricular stimulation mode and a biventricular stimulation mode of the aforementioned type. 
       SUMMARY OF THE INVENTION 
       [0008]    An objective of the invention is to provide a cardiac stimulator that will allow efficient cardiac resynchronization therapy (CRT). The invention includes an implantable cardiac stimulator having at least one first sensing unit for detecting intrinsic cardiac activities of a first ventricle, which has an input that is or can be connected to a first electrode line. The first sensing unit is designed to analyze an electric input signal applied at its input, such that the sensing unit detects at least one signal feature that is typical of a contraction of the first ventricle and creates a corresponding output signal. Furthermore, the cardiac stimulator has at least one stimulation unit for stimulating a respective second ventricle of the heart, which has an output that is or can be connected to a second electrode line. The stimulation unit is designed to generate a ventricular stimulation pulse in response to a control signal and deliver it via the output. A stimulation control unit is connected to the first sensing unit and the stimulation unit and is designed to process output signals of the sensing unit and to generate control signals for the stimulation unit. The stimulation control unit is configured to derive a current intrinsic RR interval from the detected ventricular intrinsic cardiac activities R of the first ventricle, and to determine from the RR interval a delay interval Δ. The delay interval Δ begins with a ventricular event of the first ventricle, and at its end, the stimulation control unit triggers stimulation of the second ventricle, unless it is inhibited. 
         [0009]    In practice, the “first ventricle” noted above is usually the right ventricle, but it may also be the left ventricle (e.g., in the case of a right-leg block). 
         [0010]    The invention is based on the finding that when a heart suitable for resynchronization has an intrinsic rhythm in one ventricle, resynchronization can be achieved only by stimulation in the other ventricle. As long as the control unit of the cardiac stimulator can detect an intrinsic rhythm in the first chamber of the heart (i.e., there is no AV block), the point in time of stimulation in the second chamber is determined according to the method described below. If there is no longer an intrinsic ventricular rhythm (e.g., AV block, sinus bradycardia), then resynchronization is preferably performed according to the traditional method (stimulation in both ventricles). For an intermittent AV block, automatic switching may be provided. 
         [0011]    Resynchronization is achieved by a delay interval Δ (see  FIG. 4 ) which is adapted beat-for-beat to the RR, the duration of the last intrinsic RR interval. The RR may optionally be calculated from preceding RR intervals, e.g., a current RR may be averaged (perhaps via a weighted average) or otherwise affected by one or more preceding RR intervals. The stimulation point in time in one of the two ventricles thus follows the respective variability of the heart rate and the intrinsic AV delay. 
         [0012]    In practice, the second (asynchronous) ventricle should be stimulated such that it contracts simultaneously with the first (intrinsically stimulated) ventricle. This can be achieved by stimulation of the second ventricle a certain interval of time VVD before detection in the first ventricle (in the same cardiac cycle). To define this point in time, stimulation is performed in the second ventricle after the interval of time Δ=RR−VVD has elapsed, starting from the intrinsic stimulation in the preceding cardiac cycle. 
         [0013]    To this end, it is also necessary to differentiate stimulation of the first ventricle by atrioventricular conduction (via the AV node) from interventricular conduction starting from the second ventricle (stimulated previously). 
         [0014]    The stimulation control unit is preferably designed to suppress (inhibit) stimulation in a particular ventricle when an intrinsic event (intrinsic ventricular activity) is detected there. 
         [0015]    The stimulation control unit is preferably designed to stimulate the second ventricle immediately (tracking) when there is a positive VVD in the case of intrinsic detection in the first ventricle before the calculated stimulation time for the second ventricle. 
         [0016]    The stimulation control unit is preferably also designed to determine the delay interval Δ, taking into account a predetermined interventricular delay time VVD. Synchronization may be refined with the help of a hemodynamic replacement variable, e.g., by adaptation of the parameter VVD [ms]. This parameter VVD indicates by how much the second ventricle (to be resynchronized) is to be stimulated before the next expected intrinsic stimulation in the first ventricle. 
         [0017]    VVD may therefore have a predetermined default value, which is stored in a memory of the cardiac stimulator. For example, the interventricular delay VVD may be determined during consultation with one&#39;s physicians. 
         [0018]    The interventricular delay time VVD may be adjusted manually to reach a hemodynamic optimum, which is derived, e.g., from intracardiac impedance, pressure sensors, imaging methods or the like. 
         [0019]    If a negative VVD (which corresponds to stimulation of the second ventricle only after detection in the first ventricle) is necessary and/or if it is obtained as an optimum value, the second ventricle is stimulated with a delay of −VVD after detection in the first ventricle of the same cardiac cycle. No RR value is needed in this case. 
         [0020]    For the case when no intrinsic stimulation is detected in the first ventricle, because it falls in the blanking period after the ventricular stimulation and therefore a direct determination of the delay interval Δ is impossible, the stimulation control unit is designed to:
   (1) Determine the delay interval Δ as the difference between the last intrinsic stimulation and the middle of the blanking interval;   (2) Alter the delay interval Δ by a correction term +delta or −delta (delta being so small that no significant influence on hemodynamics is expected, e.g., 20 ms), and to check on whether an intrinsic stimulation can be detected. If this is the case with one of the values, this correction term is retained.   (3) If this is not successful, stimulation of the second ventricle is suppressed for one or more heartbeats. If intrinsic events then occur in the first ventricle, the intrinsic RR interval and a new delay interval Δ are determined. If no intrinsic event occurs in the first ventricle (e.g., AV block or sinus bradycardia, both leading to stimulation in the first ventricle), then there is an automatic switch to normal biventricular CRT stimulation because of a lack of intrinsic conduction.   
 
         [0024]    Furthermore, the stimulation control unit is preferably designed to detect direct conduction from the second ventricle to the first ventricle by altering the delay interval Δ for one or more cycles by a period τ at regular intervals, and determining the resulting change in the RR interval. If RR also changes by τ in the same direction, the stimulation control unit detects a direct conduction and reduces the delay interval VVD. As an alternative, the pacing in the second ventricle (starting from the unwanted conduction) may be suppressed for one or more beats. 
         [0025]    In a preferred version of the invention, the implantable cardiac stimulator allows sensing in both ventricles and offers the possibility of stimulation in at least one of the two ventricles. 
         [0026]    Furthermore, it is preferred to have the blanking time after a ventricular stimulus be as short as possible in order to be able to determine the delay interval Δ with adequate precision even in the case of almost simultaneous sense events and pace events. 
         [0027]    The invention provides a number of advantages, including:
   (a) Utilizing the natural stimulus conduction in the right ventricle leads to a more efficient contraction.   (b) The natural adaptation of the AV delay time (AV delay) to various load states is utilized.   (c) The invention offers a simple concept for continuous adaptation of the VV delay with intact AV conduction.   (d) In a preferred version, the invention allows the detection of conduction from the left ventricle to the right ventricle.   (e) The invention allows lower energy consumption than traditional biventricular cardiac stimulators by reducing the frequency of RV stimulation.   (d) The invention offers a suggested approach to the clinical question: why should the right ventricle be artificially stimulated when conduction is intact?   (e) The invention also extends to automatic AV/VV optimization. If the cardiac stimulator is designed to automatically determine an optimal AV delay (an optimal atrioventricular delay time), this may lead to an optimal AVD setting, which results in an intrinsic stimulation in the first ventricle. In this case, it is possible to switch seamlessly to the method presented here.   
 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         [0035]    An exemplary version of the invention will now be explained in greater detail with reference to the accompanying figures, in which: 
           [0036]      FIG. 1 : shows a schematic diagram of a cardiac therapy system; 
           [0037]      FIG. 2 : shows a diagram of a cardiac stimulator with connected electrodes arranged in the heart; 
           [0038]      FIG. 3 : shows a schematic block diagram of a cardiac stimulator; 
           [0039]      FIG. 4 : shows an exemplary diagram of the chronological sequence of stimulation. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0040]      FIG. 1  shows a cardiac treatment system including an implanted cardiac pacemaker  10 , an external device (patient device)  90 , and a service center  92  represented symbolically by a server. The implantable cardiac stimulator  10  has a telemetry unit allowing wireless exchange of data with the external device  90 . The external device  90  is connected (e.g., by wire) to the service center  92 , for example, so that data can be exchanged between the service center  92  and the implantable cardiac stimulator  10  via the external device  90  as a relay station. Physicians  94  can then access data received by the service center  92  from the implantable cardiac stimulator  10 . 
         [0041]      FIG. 2  shows the implantable cardiac stimulator  10  in the form of a triple-chamber cardiac pacemaker/cardioverter/defibrillator with electrode lines  14 ,  16  and  30  connected thereto in combination with a heart  12 , and in the vicinity of the external device  90 . The electrode lines  14 ,  16  and  30  are electrically connected to contact bushings in a header (connecting housing)  11  of the cardiac stimulator  10  via standardized plug connections. In this way, the electrode lines  14 ,  16  and  30  are also connected to electronic components in the interior of a hermetically sealed metal housing  42  of the cardiac stimulator  10 . These components are presented schematically in greater detail below, and control the functionality of the cardiac stimulator  10 . 
         [0042]    The electrode line  14  is a right-atrial electrode line and has an atrial tip electrode (RA tip)  22  on its distal end and an atrial ring electrode (RA ring)  24  situated a short distance from the RA tip  22 . Both electrodes are placed in the right atrium  26  of the heart  12 . 
         [0043]    The electrode line  16  is a right-ventricular electrode line and has a right-ventricular tip electrode (RV tip)  18  on its distal end and has a right-ventricular ring electrode (RV ring)  20  situated nearby. Both electrodes are arranged at the apex of the right ventricle  28  of the heart  12 . The right-ventricular electrode line  16  also includes a right-ventricular shock coil (RV shock)  38  as a large-area electrode for delivering defibrillation shocks. Another shock coil  40  is arranged in the superior vena cava, and is also referred to below as an SVC shock electrode  40 . 
         [0044]    The electrode line  30  is a left-ventricular electrode line having a distal left-ventricular tip electrode (LV tip)  34 , a nearby left-ventricular ring electrode (LV ring)  32 . (A left-ventricular shock coil is also shown in  FIG. 2  on the left-ventricular electrode line  30  for delivering defibrillation shocks to the left ventricle, but this is not labeled nor discussed further.) The left-ventricular electrode line  30  is guided out of the right atrium  26  of the heart through the coronary sinus into a branching lateral vein, and therefore is also referred to as the coronary sinus electrode line  30  or CS electrode line  30 . 
         [0045]      FIG. 3  schematically illustrates the foregoing components of the cardiac stimulator  10 . The electric terminals for the various electrodes  18 ,  20 ,  22 ,  24 ,  32 ,  34 ,  38  and  40  are shown on the left side. The shock electrodes  38  and  40  are each connected to a right-ventricular shock pulse generator RV-Shock  50  and/or an SVC shock pulse generator SVC-Shock  52 . Both of the shock generators  50  and  52  are connected to a stimulation control unit  54 , which controls the two shock pulse generators  50  and  52  as needed to generate and deliver a defibrillation shock. A similar shock pulse generator can be implemented for the left ventricular shock electrode (not labeled in  FIG. 1 ). 
         [0046]    The terminal for the right-ventricular tip electrode RV tip  18  and the terminal for the right-ventricular ring electrode RV ring  20  are both connected to a right-ventricular stimulation unit  56  and a right-ventricular sensing unit  58 . Both the right-ventricular stimulation unit  56  and the right-ventricular sensing unit  58  are connected to the stimulation control unit  54 . 
         [0047]    The right-ventricular stimulation unit  56  is designed to generate a right-ventricular stimulation pulse in response to a triggering signal of the stimulation control unit  54  and to subsequently deliver the stimulation pulse to the right-ventricular tip electrode  22  and the right-ventricular ring electrode  20 . Alternatively, it is also possible for the housing  42  of the cardiac stimulator  10  to form a neutral electrode and for the right-ventricular stimulation unit  56  to be connected to the terminal for the right-ventricular ring electrode  18 , with the housing  42  defining another electrode for delivering a stimulation pulse. A right-ventricular stimulation pulse differs from a defibrillation shock in that the stimulation pulse has a much lower pulse intensity, so it does not stimulate all the cardiac tissue (myocardium) of a heart chamber simultaneously like a defibrillation shock, but instead stimulates only the myocardial cells in the immediate vicinity of the right-ventricular tip electrode  18 . This stimulation then propagates through natural stimulus conduction over the entire ventricle and thus ensures a stimulated contraction of the ventricle. 
         [0048]    The right-ventricular sensing unit  58  is designed to first amplify and filter the electric potentials applied to the terminal for the right-ventricular ring electrode RV ring  20  and the right-ventricular tip electrode RV tip  18  through an input amplifier (not shown). In addition, the right-ventricular sensing unit  58  is designed to analyze the characteristics of the electric signals applied at its inputs, so that the right-ventricular sensing unit  58  automatically detects an intrinsic (i.e., natural or independent contraction) of the right ventricle. This may take place, for example, by comparing the characteristics of the signal applied at the inputs of the right-ventricular sensing unit  58  with a threshold value. The greatest amplitude of the signal in the form of the so-called R wave is typically characteristic of a natural contraction of the right ventricle, which can be detected by threshold value comparison. The right-ventricular sensing unit  58  then delivers a corresponding output signal indicating a natural contraction of the right ventricle to the stimulation control unit  54 . 
         [0049]    Similarly, the terminal for the right-atrial tip electrode  22  and the terminal for the right-atrial ring electrode  24  are connected to a right-atrial stimulation unit  60  and also to a right-atrial sensing unit  62 , each being in turn connected to the stimulation control unit  54 . The right-atrial stimulation unit  60  is designed to generate stimulation pulses having a sufficient intensity to stimulate the right-atrial myocardium. The right-atrial stimulation pulses may have a different pulse intensity than the right-ventricular stimulation pulses. The right-atrial sensing unit  62  is designed to detect a so-called P wave from the differential signal applied at its input, said P wave being characteristic of an intrinsic (natural) contraction of the right atrium. If the right-atrial sensing unit  62  detects a corresponding P wave, it generates an output signal and sends it to the stimulation control unit  54 , identifying a natural contraction of the right atrium. 
         [0050]    In the same way, the terminal for the left-ventricular tip electrode LV tip  34  and the terminal for the left-ventricular ring electrode LV ring  32  are each connected to a left-ventricular stimulation unit  64  and a left-ventricular sensing unit  66 . The left-ventricular stimulation unit  64  and the left-ventricular sensing unit  66  are likewise connected to the stimulation control unit  54 . Both of them function like the stimulation units  56  and  60  and the sensing units  58  and  62  already described above. 
         [0051]    In addition, the cardiac stimulator  10  includes a memory unit  80 , which is connected to the stimulation control unit  54  and makes it possible to store signals generated or analyzed by the stimulation control unit  54 . The memory unit  80  may also or alternatively be used to store control programs for the stimulation control unit  54  in a modifiable form. Most preferably, the memory unit  80  stores values of the most recent intrinsic RR intervals plus at least one value for an interventricular delay time VVD. 
         [0052]    Furthermore, the stimulation control unit  54  is connected to a timer  84 , which enables the stimulation control unit  54  to determine matter such as points in time and intervals of time. 
         [0053]    The memory unit  80  is connected to a telemetry unit  82 , which makes it possible to wirelessly transmit data stored in the memory unit  80  to the external device  100 , or to transmit programming commands from the external device  100  to the cardiac stimulator  10  and store them in the memory unit  80 . 
         [0054]    As a triple-chamber cardiac stimulator/cardioverter/defibrillator, the cardiac stimulator  10  is capable of stimulating the right atrium, the right ventricle and the left ventricle or just one or two of these cardiac chambers in a known manner. This includes in particular stimulation of the respective cardiac chamber in demand mode, in which stimulation pulses are delivered to the respective cardiac chamber only when no intrinsic contraction of the respective cardiac chamber is detected by the respective sensing unit in a preceding respective escape interval. The cardiac pacemaker is thus capable of performing the known right-ventricular stimulation modes such as VVI, VVD or DDD. 
         [0055]    For the timing of the stimulation pulses in the biventricular stimulation mode in which both ventricles of a heart are stimulated, an interventricular delay time (VV interval; VVD) is particularly important: this is the time by which a right stimulation pulse and a left stimulation pulse follow one another, if they are not inhibited in demand mode. This time may be less than 0, so the left stimulation pulse trails behind the right stimulation pulse. The interventricular delay time may be 0, which means that a right-ventricular stimulation pulse and a left-ventricular stimulation pulse are delivered simultaneously by simultaneous triggering of the right-ventricular stimulation unit  56  and the left-ventricular stimulation unit  64 . The interventricular delay time may also be greater than 0, which means that a left-ventricular stimulation pulse is delivered before the delivery of the respective right-ventricular stimulation pulse. 
         [0056]    The stimulation control unit  54  is designed to achieve a resynchronization of the right and left ventricles using at least one electrode in both the right and left ventricles. Stimulation in one of the two ventricles is suppressed by the stimulation control unit  54  when the respective sensing unit detects an intrinsic event there. 
         [0057]    For resynchronization, the stimulation control unit  54  determines a delay interval Δ (see  FIG. 4 ) which is adapted beat-for-beat to the duration of the last intrinsic RR interval. An optimization is performed here with the help of a hemodynamic replacement variable, for example, through the adaptation of a parameter VVD [ms]. This parameter VVD corresponds to an interventricular delay time and indicates by how much the ventricle to be resynchronized is to be stimulated before the next expected intrinsic stimulation. 
         [0058]    The stimulation point in time in one of the two ventricles thus follows the respective variability of the heart rate and the intrinsic AV delay. 
         [0059]    A suitable value for VVD is stored in the memory  80 . It may be determined by a physician during a consultation, for example. VVD is varied to search for a hemodynamic optimum derived from intracardiac impedance, pressure sensors, imaging methods or the like, for example. 
         [0060]    For the case when an intrinsic stimulation of the right ventricle is not detected because it falls in the blanking time after the ventricular stimulation and therefore a direct determination of the delay interval Δ is impossible, the stimulation control unit  54  determines the delay interval Δ as the difference between the last intrinsic stimulation and the middle of the blanking interval. 
         [0061]    If that is not successful, the stimulation control unit  54  suppresses stimulation of the left ventricle for one heartbeat to measure the intrinsic RR and determine from that a new delay interval Δ. 
         [0062]    The stimulation control unit  54  is also designed to detect direct conduction from the left ventricle to the right ventricle (or vice versa) at regular intervals by reducing the delay interval Δ by τ for one or more cardiac cycles, and measuring the resulting change in the RR interval. If the RR also changes by τ, then there is probably direct conduction. In this case, the stored value for the interventricular delay time VVD is reduced. 
         [0063]      FIG. 4  shows an example of stimulation of the left ventricle with intermittent intact natural contraction of the right ventricle. Left-ventricular events are shown in the upper part of the figure, while right-ventricular events are shown in the lower part; stimulated (paced) events are labeled as Vp and intrinsic (sensed) events are labeled as Vs. 
         [0064]    The stimulation control unit  54  uses the period of two successive intrinsic right- or left-ventricular contractions, detected by the respective sensing unit  58  or  66 , for determination of an optimal delay interval Δ between a right-ventricular event and a left-ventricular pace event, i.e., the point in time at which a left-ventricular stimulation pulse is to be delivered. The first intrinsic RR interval RR 1  is used together with a stored value for the interventricular delay time VVD for determining the first delay interval Δ 1 : 
         [0000]      Δ 1   =RR 1− VVD [ms]
 
         [0065]    By analogy, the next delay interval Δ 2  is determined from the next intrinsic RR interval RR 1  and with this, the point in time of the next left-ventricular stimulation pulse is determined: 
         [0000]      Δ 2   =RR 2− VVD [ms]
 
         [0066]    In the selected example, stimulation of the left ventricle takes place simultaneously with the right intrinsic stimulation because the heart rate (HR) has increased. The next stimulation in the left ventricle, following the higher HR, is accordingly stimulated sooner: 
         [0000]      Δ 3   =RR 3− VVD [ms]
 
         [0067]    In the example, the next intrinsic R interval is again longer because the heart rate has slowed. Therefore, the delay interval Δ 4  between the next intrinsic event and the stimulation of the left ventricle is automatically longer: 
         [0000]      Δ 4   =RR 4− VVD [ms]
 
         [0068]    With the formation of the next delay interval Δ 5  the adaptation to the delayed heart rate is concluded: 
         [0000]      Δ 5   =RR 5− VVD [ms]
 
         [0069]    It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and versions are possible in light of the foregoing discussion. The disclosed examples and versions are presented for purposes of illustration only, and this patent extends to cover all alternative versions of the invention that fall literally within the scope of the claims below, as well as all equivalents of the claimed inventions.