WO2003002195A2

WO2003002195A2 - Pacemaker with periodic modulation of individual stimulation intervals

Info

Publication number: WO2003002195A2
Application number: PCT/EP2002/006347
Authority: WO
Inventors: Karl Stangl; Roland Heinze
Original assignee: Karl Stangl; Roland Heinze
Priority date: 2001-06-29
Filing date: 2002-06-10
Publication date: 2003-01-09
Also published as: WO2003002195A3; DE10132228C1

Abstract

The invention relates to a pacemaker comprising a device for measuring at least one heart function parameter and a device modulating individual stimulation intervals in such a way that the degree of modulation is regulated depending on the duration of the diastolic interval and on changes in heart function parameters provoked by the modulations so that given phases of electrical and mechanical restitution can be detected independently of systolic duration while accuracy remains unchanged.

Description

Pacemaker with periodic modulation of individual stimulation intervals

The invention relates to a pacemaker according to the preamble of the main claim.

When further developing metrological or diagnostic functions of cardiac pacemakers to optimize the stimulation parameters, a distinction must be made between two tasks, namely the improvement of sensor technology on the one hand and the optimization of the measurement method and signal analysis on the other.

The present invention is based on work which can be assigned to the second task and which pursue the known measurement methodical approach of evoking reactions through targeted stimulation in the measurement object, which reflect specific functional properties of the measurement object and which would not be detectable or differentiable without stimulation.

The artificial stimulation of the heart by the pacemaker offers the opportunity to record the passively non-measurable characteristics of the electrical and mechanical restitution. By modulating individual so-called extrasystolic stimulation intervals, the duration of the diastolic regeneration or restitution process of the heart is changed, which changes in the following (extra) systolic interval. probably evoked the action potential as well as the contraction force of the myocardium and thus in combination with the likewise changed preload and afterload leads to a changed stroke volume of the ventricle. Both processes, both the diastolic restitution and the reaction of the following (extra) systolic cardiac functions, which decreases with increasing diastolic shortening and which is defined as a systolic restitution characteristic, have an exponential course. Since both processes correlate with each other, it is possible to analyze the diastolic regeneration using the restitution characteristic, even if it cannot be measured directly with the available measurement parameters, such as electrical restitution using the ECG. The time constant of the regeneration or restitution characteristic is of central importance, since it provides information about the adaptation dynamics of the myocardium, and thus information about the current level of stress on the heart and its performance reserve. However, this information is not only essential for optimal control of the pacemaker functions, such as the stimulation rate, but also generally for diagnostic purposes.

The modulation of individual stimulation intervals in cardiac pacemakers and the analysis of the resulting specific changes in cardiac function parameters to improve the frequency control are known. Three embodiments have been described which apply the modulation principle. For example, it has been proposed to calibrate the impedance measurement values and to filter interference signals in intracardiac impedance measurements to determine the stroke volume (DE 40 31 450 Cl). Furthermore, the single pulse modulation with different degrees of modulation and different stimulation frequencies zen proposed to detect characteristic reaction patterns of intracardiac measurement parameters and to use their change behavior for diagnosis and frequency control (DE 44 47 447 C2). In another approach, the method of single pulse modulation was used to analyze the gradient of the electrical restitution characteristic and to use it as a control parameter for continuous frequency control (DE 199 00 690 Cl).

With the concepts mentioned, it has proven to be disadvantageous that the modulation of individual stimulation intervals (ESI) is carried out in fixed modulation periods and with a modulation amplitude that is fixed as a percentage of the base cycle length or mean stimulation interval duration. Since the duration of systolic or diastolic function intervals can fluctuate not only individually, but mainly as a result of (patho-) physiological changes in the myocardium, this means that with an extrasystolic stimulation pulse based on the basic cycle length, the measurement is falsified because different phases diastolic restitution. For example, the evaluation of the restitution characteristic in the known form leads to the behavior of the slow restitution phase having a time constant Trl of approximately 400 to 1000 ms being primarily analyzed at a low stimulation frequency, and the influence of the fast restitution phase having a time constant Tr2 of primarily being analyzed at a high stimulation frequency about 100 to 200 ms. This means that processes that lead to different reactions between the specific myocardial time constants Trl and Tr2, such as the administration of chronotropic or inotropic drugs, cannot be differentiated. In addition, acute non-specific fluctuations As a result of systolic intervals, such as the extension of the QT interval at the start of exercise, the restitution analysis is falsified, which - if at all - can only be compensated for with complex correction calculations during signal analysis.

Furthermore, the interval modulations carried out symmetrically to the mean duration of the stimulation intervals make it necessary to severely restrict either the maximum stimulation frequency or the degree of modulation with an increased stimulation frequency in order to rule out stimulation in the refractory area of the myocardium in the case of the shortened stimulation intervals. However, this restriction leads to a critical reduction in the sensitivity of the measurement method, which can prove to be critical for the use of the measurement method in the case of the large interference factors which are to be taken into account in principle in the pacemaker area. This has a particularly disadvantageous effect with the previous form of modulation if it is used in two-chamber pacemakers, since here the modulation dynamics are additionally restricted by the duration of the AV interval.

In another concept, the modulation of individual stimulation intervals of the atrium was described in order to analyze the extent to which changes in the duration between atrial and autonomic ventricular stimulation (AV interval) are brought about

(DE 36 25 894). Ultimately, this modulation also serves to optimize the stimulation frequency, but like the previous approaches, it is unregulated, i.e. without control of systolic or diastolic function profiles, apart from the fact that this principle is only suitable for the special case of atrial stimulation, because here a parameter, namely that AV Interval, is investigated, which is regulated in the normal two-chamber pacemaker by the system itself.

The object of the invention is to control the modulation of individual stimulation intervals in cardiac pacemakers in such a way that an analysis of the electrical or mechanical restitution is possible not only in a phase-specific manner but also more precisely and reliably in the entire range of the stimulation frequency.

This object is achieved by the features of the main claim.

In contrast to the previous systems, the pacemaker according to the invention does not modulate the stimulation intervals in a fixed manner based on the basic cycle length or mean stimulation interval duration, but instead depends both on the diastole duration and on the value of the modulations of the cardiac function parameter to be examined evoked by the interval modulations. This not only extends the range of the stimulation frequency within which the method can be used, but also enables a more precise and phase-specific analysis of the electrical and mechanical restitution characteristics.

For the phase-specific sampling of the diastolic restitution, an extrasystolic modulation value is first calculated, in which the diastole duration of the modulated interval has a value which can be predetermined by the program control and which defines the middle of the sampling phase and which, since it is fixed in relation to the beginning of the diastole , is independent of fluctuations in the systolic interval. In relation to the phase center determined in this way, two further extra systolic modulation values are calculated in such a way that a modulation symmetrical to the phase center takes place, the modulation stroke, which determines the width of the phase to be scanned, being regulated as a function of the measurement modulation, in order to ensure on the one hand a minimum modulation level and thus a minimum basic accuracy and on the other hand to keep the modulation of the stimulation intervals as small as possible in order to deviate as little as possible from the normal stimulation.

The start of electrical restitution is detected as standard by triggering the T wave of the ventricular ECG. In contrast, a precise detection of the beginning of the mechanical restitution requires an additional sensor which, like pressure sensors or acoustic sensors, is able to indicate the opening or closing of the pulmonary valves and the AV valves.

When using interval modulation in two-chamber pacemakers, it must be checked whether the duration of the electrical diastole of the ventricle, multiplied by an amount less than 1, is reduced to a value less than the AV in one of the two extrasystolic interval changes -Interval at basic cycle length. In this case, the AV interval of the extrasystolic interval must be shortened accordingly to avoid stimulation in the area of the refractory phase of the myocardium. However, since an AV interval shortening can have an influence on the restitution characteristic - especially the mechanical one - to compensate for this influence, it is advisable to carry out the same AV interval shortening for all extrasystolic modulations. Furthermore, it has been shown that, especially in the case of frequent changes between spontaneous and artificial stimulation of the heart muscle, it is advisable not to correct the errors that occur only when evaluating the signal, but rather to make the modulation dependent on the type and duration of the previous stimulation pulses. Since the spread of stimuli and, accordingly, the contraction of the heart muscle change depending on the form of stimulation, and this change process continues at least over two pulse cycles, it is advantageous to start the modulation at the earliest two cycles after spontaneous stimulation. If, on the other hand, the spontaneous stimulation lasts over several pulse cycles, it is advisable to wait about as many cycles afterwards, but at most one minute before the next modulation, since the changed contraction usually also changes the cardiac output and thus the hemodynamic values of the entire circulatory system can.

The first step in the analysis of the restitution phase to be examined is the determination of the changes in measured values evoked by the two interval changes. For this purpose, first the values of the extrasystolic pulse cycles following a modulation as well as those of the next so-called post-extrasystolic pulses are recorded and then the difference values are then determined therefrom. In addition to the extrasystolic difference values, which reflect the course of the respective restitution characteristics within a defined phase, the difference values of the subsequent so-called post-extrasystolic measurement values are also physiologically interesting, since they describe the degree of compensatory effects in the myocardium. Since the time constant of the exponential restitution processes provides the most accurate information about the speed of regeneration of the myocardium, their determination is the actual goal of the signal evaluation. To do this, however, it is necessary to carry out at least a third interval change, which is expedient to be half the sum of the other two, so that it scans the center of the phase, in order to be able to use a simple calculation algorithm.

As mentioned above, two characteristic phases can be distinguished in the restitution of the electrical as well as the mechanical properties of the myocardium, which is why the interval modulations must be dimensioned accordingly so that these two phases, namely the early and late diastolic phase , can be recorded separately. It has proven to be advantageous that, depending on the modulation to be optimized

Pacemaker function the control of the modulation periods is designed so that both a parallel and a sequential recording of the parameters of both restitution phases is possible.

To accept the modulation of individual stimulation intervals for restitution analysis, it is not only advantageous to carry out the modulation as small as possible, but also rarely as possible. It is therefore expedient to use the late diastolic scanning phase in longer periods of rest and to scan a longer modulation period, whereas the early diastolic phase with larger load fluctuations or higher loads, and to set the shorter modulation periods. Since the phase-specific analysis of the electromechanical restitution can provide information about both the power reserve of the myocardium and its adaptation dynamics, it can be used in practically all frequency-controlled pacemaker systems. Since all systems enable a ventricular ECG measurement, the analysis of the electrical restitution can be used practically universally, while the analysis of the mechanical restitution is only used for the systems that also have a sensor for contraction measurement.

For example, the analysis of the electrical restitution is very well suited to be used in a pacemaker whose stimulation frequency is regulated depending on the duration of the QT or Stim-T interval. Here, the stimulation frequency is then set exclusively in phases of larger load fluctuations or higher loads, depending on the control signal that provides the regulation of the interval modulations, while in phases of rest or when the load is constant, the stimulation frequency depends on the value of the Stim-T interval is determined. Since the restitution analysis not only provides the faster, but also the more precise load parameter (e.g. the time constant), it is possible to dynamically calibrate the control range of the QT control using the restitution analysis, so that the transition from one control parameter to the other without critical frequency jumps can occur.

After the behavior of the time constant of the mechanical restitution, particularly in the higher load range, indicates very precisely whether the adaptation dynamics of the heart muscle has already been exhausted, i.e. whether the increase in the stimulation frequency leads to an improved If the pumping performance is not or does not work, the analysis of the mechanical restitution is suitable for the hemodynamic optimization of pacemakers who record mechanical cardiac function parameters with an intracardiac sensor.

In patients who have implanted a pacemaker for prophylactic reasons, interval modulation with the aid of artificial extrasystolic stimulation pulses offers an additional analytical approach for diagnostic purposes, which can be used above all for the early detection of pathological changes in the myocardium such as ischemia.

An embodiment of the invention is shown in the drawings and is explained in the following description. Show it:

FIG. 1 shows the characteristic time delay between electrical and mechanical restitution processes during diastole in the right ventricle;

2 shows the time course of the atrial and ventricular stimulation interval as well as the ventricular EKG and pressure gradient dP / dt when a single pulse interval is shortened;

3 shows the functional diagram of the extrasystolic

Stimulation intervals for scanning the early diastolic phase of the electrical restitution over the entire range of the basic cycle length BCL, namely

a) the ventricular pacing intervals ESI1 and ESI2; b) the associated atrial pacing intervals VAIesl and VAIes2;

4 shows the greatly simplified block diagram of a single-chamber pacemaker according to the present invention and

5 shows the greatly simplified block diagram of a two-chamber pacemaker according to the present invention.

Based on the schematic signal curve of the most important functional parameters of the right ventricle, FIG. 1 shows that when analyzing the electromechanical restitution of the heart during diastole, a distinction must be made between three differently long, exponential processes. The temporal basis for the cardiac cycle and the ratio of systolic to diastolic time interval is primarily determined by the (basic) cycle length (BCL) between the stimulation pulses and by the duration of the action potential (APD), i.e. the change between depolarization and repolarization of the muscle cells - true, as track 1 and 2 in Fig. 1 show. Since the start of repolarization is reflected in the T-wave of the ECG and the stimulus determines the start of the QRS complex, in practice the maximum of the T-wave is defined as the end of the systole and the start of the diastole, that is, as " electrical diastole '. The TQ interval applies. Physiologically correct, the repolarization begins with the drop in the action potential, which coincides with the beginning of the T wave, so that for a correspondingly accurate analysis of the electrical restitution, the diastolic interval duration DI _E is to be used. The contraction and relaxation of the heart muscle following depolarization and repolarization is characterized by four characteristic points in time (PI to P4) which determine the hemodynamics of the heart and determine the opening and closing of the two valves in the right and left ventricles. As can be seen in the fourth track, the pressure increase in the ventricle via the atrial pressure (dashed lower line) leads to the closing (PI) of the AV valve and in the further course when the pulmonary artery pressure is exceeded (upper dashed line) Open (P2) the pulmonary valve. Conversely, relaxation after repolarization of the ventricle first causes the pulmonary valve to close (P3) and then to open (P4) the AV valve. Accordingly, the mechanical or active diastole is defined as the time interval (T31) between the beginning and end of the relaxation phase, which coincides with the closing of the two heart valves. Practically, the opening and closing of the valves can be determined by the gradient of the ventricular pressure, as the 5th trace shows. This means that the mechanical diastole corresponds to the interval between the beginning of the negative and positive pressure gradient, detectable via a threshold trigger.

The last stage of the mechanical restitution is the filling of the ventricle, which exponentially increases after opening the AV valve (P4), the course of which is shown in lane 6 of FIG. 1. The interval of the diastolic ventricular filling, i.e. the time from opening (P4) to closing (Pl) of the AV valve, can - as track 5 shows - also be determined using the pressure gradient using a threshold trigger. As the signal curves illustrate, the three diastolic regeneration or restitution processes differ in terms of the beginning or their duration. A phase-specific analysis of the respective restitution does not only require an exact assignment at the beginning of the restitution, but above all because of the possible strong fluctuations in the systolic time interval as a result of pathological changes such as in Long QT syndrome.

In Fig. 2, depending on the shortening of a single ventricular stimulation interval ESI shown in lane 1, both the necessary change in the AV interval (lane 2) and the typical response of the ventricular ECG (lane 3) and in the two subsequent pulse cycles is shown of the pressure gradient dP / dt (track 4). Since the function of the ventricle is in the foreground when analyzing diastolic restitution in the heart muscle, the ventricular stimulation pulse is defined as the time reference point for describing the temporal relationships, although the atrial stimulus functionally precedes it by the so-called atrioventricular interval (AVI). At the basic cycle length (BCL), the atrial stimulus of the next pulse follows the ventricular stimulus with an interval VAIb = BCL - AVIb.

As tracks 1 and 2 show, in the case of a stimulation interval shortened by -ΔESI (ESI), the AV interval (AVIb) must also be shortened (by -ΔAVes) so that the atrial stimulus does not fall into the refractory period (RP) of the heart muscle (see Fig. 1). The end of the refractory phase or period can be determined by detecting the end of the T wave or, in a simplified manner, can be calculated using the QT interval multiplied by a specific factor (a). prin- The following applies in particular if: AVIb> Dies = ESI - RP the AV interval is reduced by ΔAVes = Dies - AVIb and the following results accordingly for the extrasystolic atrial interval calculated from the ventricular stimulus: VAIes = ESI - AVIb + ΔAVes

As a result of the shortened diastolic interval (dies), the following "extrasystolic" interval results in a reduction of the QT interval by -ΔQTes (lane 3) as well as the maximum values of the pressure gradient dP / dtmax by -ΔdPmaxes and dP / dtmin by ΔdPmines (Lane 4) In the second so-called "post-extrasystolic" interval following the interval change, a compensatory effect then follows, which leads to an extension of the QT interval by ΔQTpes or to a potentiation of the pressure values by dPmaxpes and dPminpes.

The diagrams a) and b) in FIG. 3 are to be used as an example to show how extrasystolic

Modulations a specific phase of electrical restitution can be sampled. Diagram 3a) shows, depending on the basic cycle length (BCL), the typical course of a QT interval (QTb) and - in broken lines - the corresponding refractory period (RP) as well as the course of three extrasystolic intervals (ESI0, ESI1 and ESI2). Here, ESI0 defines the middle of the diastolic restitution phase that is to be analyzed (sampling phase). This center value is sampled by the interval modulation ΔESI0, the value of which is determined depending on the electrical diastole DI _E by the relationship: ΔESI0 = DI _E -K1-K2, where Kl is a predeterminable constant interval value and K2 one of the basic cycle length dependent correction value. The modulation values ΔESI1 and ΔESI2 and thus the modulation deviation ΔESI12 of the stimulation intervals are dependent controlled by the modulation stroke or the difference (ΔMesl2) of the ΔESI1 and ΔESI2 following extrasystolic measured values (Mesl and Mes2). The regulation of the modulation values is intended to prevent the measurement parameter modulation from falling below a minimum level (ΔMesmin) by increasing the modulation stroke (ΔESI12). If one assumes a linear relationship between ΔESI12 and ΔMesl2 within the sampling phase, the modulation stroke ΔESI12 can be determined using the following simplifying equation: ΔESI12 = ΔESImax - Fv * ΔMesl2, where the factor Fv is the control gain of the closed control loop and ΔESImax is a maximum permissible modulation stroke Are defined. This results in the symmetrical modulation required around the phase center defined by ESIO, that is, because ΔESI1 - ΔESIO = ΔESIO - ΔESI2:

ΔESI1 = ΔESIO - (ΔESImax-Fv * ΔMesl2) / 2 and ΔESI2 = ΔESIO + (ΔESImax-Fv * ΔMesl2) / 2

The increase in the sampled time window (ESI1-ESI2) and its distance from the refractory period (RP) with increasing base cycle length is intended to compensate for the influence of the stimulation frequency on the slope of the restitution and thus on the measured value modulation ΔMesl2, that is to say ΔMesl2 should remain the same if not the stimulation rate does not change any additional influencing factors.

3b) shows the courses of the atrial stimulation intervals (VAIesl and VAIes2) belonging to the extrasystolic, ventricular stimulation intervals (ESI1 and ESI2) when using a two-chamber pacemaker as well as the QTb and VAIb interval. The dashed lines indicate the course of the atrial stimulation intervals if the base value of the AV interval (AVIb) was used when calculating the atrial, extrasystolic intervals (VAIesl and VAIes2). In order to prevent the shorter stimulation interval (VAIesl) from becoming smaller than the refractory period (RP = a * QTb), the AV interval must be reduced by ΔAVIesl in the simplest form so that the VAIesl values are equal to the RP values as shown in diagram 3a). Since in the constellation shown the value for AVIb for each basic cycle length is greater than the difference between the shortest, extrasystolic interval ESI1 and a * QTb, all extrasystolic AV intervals AVesl and AVes2 are shortened by the amount: ΔAVes = ESI-a * QTB-AVIb.

4 shows the greatly simplified block diagram of an exemplary embodiment of the pacemaker which, in addition to the known functions, enables the modulation of individual stimulation intervals depending on the duration of the diastolic interval and the amplitude of the evoked modulations of a cardiac function parameter for the phase-specific analysis of diastolic restitution processes.

The mode of operation of the pacemaker can generally be divided into four higher-level functional units, namely the pacemaker circuit (14), which stimulates the heart via an electrode (1), and the program control (12), which controls all the pacemaker's functional processes either according to permanently programmed criteria or set by an external programming device (13) is checked according to variable criteria. The pacemaker (1) itself also shows five higher-level function blocks that represent the basic functions. All sensor signals used are - here it is only the ECG derived via the stimulation electrode (11) - amplified in a signal amplifier stage (2) and further processed in a signal analysis stage (3), which is primarily used for the detection of brady- and tachycardiac cardiac arrhythmias, but generally carries out the analysis of cardiac function parameters, the results of which are then used in the following control stage (4) to control the antibrady- and antitachycardic interventions of the pacemaker via the setting of the stimulation intervals (9) and the final stimulation pulse generator (10). In addition to the standard functions mentioned, the pacemaker according to the invention contains a function stage (7) which automatically controls the chronological sequence of the modulation of individual stimulation intervals in the control stage (9) and the demodulation of the evoked modulations of the function parameter in the signal analysis stage (3) according to predetermined criteria. For this purpose, the period control (7) receives the information via the signal analysis (3) whether it is detected

Heart action is a spontaneous arousal or an artificial stimulation. Accordingly, it interrupts or starts the periodic modulation of individual stimulation intervals and sets the period duration depending on the value and the change behavior of the pulse rate.

The essential additional function according to the invention is, however, part of the control stage (4), which in the normal case, in addition to the antitachycardes not specified here

Control functions primarily regulate the stimulation frequency (SR) or the basic cycle length (BCL) in the BCL controller (8), the QT interval being used as a control variable in the example shown, which is obtained via the connection (31) from the signal analysis stage (3 ) is delivered. In addition, the control stage (4) contains a control (6) here extrasystolic modulation values (ΔESI) and receives from the signal analysis (3) via the connection (33) the value of the electrical diastole duration (DI _E ) and via the connection (34) the value of the modulation of the function parameter (ΔQTesl2), which they according to evaluated in Fig. 3a) criteria.

With the control signal for interval modulation of the ΔESI controller (6), however, the BCL controller (8) has an additional load parameter available which can be used to compensate for the disadvantages of the QT interval as a control parameter, namely a lack of response speed and accuracy , Instead of the control signal for interval modulation, the calculated time constant (Tr) of the electrical restitution for optimizing the BCL control in (8) can also be adopted directly from the signal analysis stage (3) via the connection (32).

5 shows the greatly simplified block diagram of an exemplary embodiment of the pacemaker, which, in addition to the modulation of individual ventricular, also enables the atrial stimulation intervals via the functions described in FIG. 4 and also uses a mechanical sensor (11).

The controller (8) not only determines the values of the basic cycle length (BCL), but also those of the AV interval (AVIb) and outputs them to the interval controller (9). Accordingly, the controller (6) not only supplies the extrasystolic modulation values ΔESI, but also - if necessary - the modulation values of the AV interval (ΔAVIes).

Claims

claims

1. Cardiac pacemaker with a device for measuring at least one cardiac function parameter (M), with a device for regulating the mean stimulation intervals such as the basic cycle length (BCL) with ventricular stimulation and the AV interval (AVI) with additional atrial stimulation depending on changes (ΔM) of the function parameter (M), and a device for periodically modulating individual so-called extrasystolic stimulation intervals (ESI) by a modulation value (ΔESI), characterized in that a device for regulating the interval modulation (6) modulates the values (ΔESI) depending on the duration of the diastolic interval (DI) and depending on the extrasystolic modulations of the function parameter (ΔMes) evoked by the interval modulations (ΔESI).

2. Pacemaker according to claim 1, characterized in that the regulation of the interval modulation

(6) preferably regulates the modulation values such that a first modulation value (ΔESIO) is determined as a function of the duration of the diastolic interval at the basic cycle length (DIb), so that the duration of the diastole before the extrasystole (Dies) has a predeterminable value, and that two further extrasystolic modulation values (ΔESI1 and ΔESI2) are determined, the difference between them and the first modulation value (ΔESI01 and ΔESI02) is the same and the difference with each other (ΔESI12) is inversely related to the difference (ΔMesl2) of the modulations of the function parameter they evoked ( ΔMesl and ΔMes2).

3. A pacemaker according to claim 1 or 2, characterized in that the regulation of the interval modulation (6) for calculating the first modulation value (ΔESIO) preferably uses the duration of the electrical diastole (DI _E ) determined with the help of the ventricular ECG and for analysis the mechanical restitution preferably the duration of the mechanical diastole (DI _M ) determined with the help of the ventricular pressure gradient (dP / dt).

4. Cardiac pacemaker according to one of claims 1 to 3, characterized in that the regulation of the interval modulation (6) with two-chamber stimulation also modulates the atrioventricular interval (AVI), preferably in such a way that at each extrasystolic interval (ESI *) the AV Interval is shortened by an AV modulation value (ΔAVIes) if the difference between the shortest extrasystolic interval (ESI2) and the refractory period (RP) is smaller than the AV interval at basic cycle length (AVIb).

5. Pacemaker according to one of claims 1 to 4, characterized in that the control of the

Modulation period (7) the interval modulation only starts if at least two artificially stimulated pulse cycles of the heart precede in phases of predominantly pacemaker stimulation or at least two self-rhythms in phases of predominantly autonomous stimulation.

6. Pacemaker according to one of claims 1 to 5, characterized in that the control of the modulation period (7) controls the signal analysis and demodulation (3) such that in addition to the directly the extrasystolic intervals (ESI1 and ΔESI2) following extrasystolic measured values (Mesl and Mes2) of the function parameter (M) also the postextrasystolic measured values following in the next pulse cycle (Mpesl or Mpes2) are determined and that the difference values of the extrasystolic and postextrasystolic measured values (ΔMesl2 and ΔMpesl2 ) be determined.

7. pacemaker according to one of claims 1 to

6, characterized in that the signal analysis (3) as a further characteristic variable of the restitution phase determined by the interval modulations (ΔESI1 and ΔESI2) determines the time constant of the exponential restitution characteristic (Tr) and preferably with the aid of the first extrasystolic interval modulation (ΔESIO) and the first extrasystolic measured value (MesO) calculates a second extrasystolic difference value (ΔMesOl) compared to the measured value (Mesl) recorded after the shorter modulation (ΔESI1).

8. pacemaker according to one of claims 1 to

7, characterized in that the regulation of the interval modulations (6) also determines modulation values for a second sampling phase, and the control of the modulation period (7) modulates the stimulation intervals (ESI *) and demodulates the measured values ( Mes) controls so that at least two different restitution phases can be scanned both sequentially and in parallel.

9. pacemaker according to one of claims 1 to

8, characterized in that the analysis of the electrical restitution is preferably used in order to optimize the response speed and the accuracy of a pacemaker in the event of load changes. The stimulation frequency is regulated depending on a function parameter that is too slow, such as the QT interval or breathing, or an unphysiological parameter, such as the activity.

10. Cardiac pacemaker according to one of claims 1 to 9, characterized in that the analysis of the electrical and mechanical restitution is preferably used to automatically optimize the values for the minimum or maximum stimulation frequency in phases of rest or maximum stress.

11. Cardiac pacemaker according to one of claims 1 to 10, characterized in that the analysis of the electrical and mechanical restitution is used to monitor the function of the myocardium for diagnostic purposes in phases of predominantly autonomous stimulation of the heart.