Evoked response detector and a heart stimulator with such a detector

Technical Field

The present invention relates to an evoked response detector for a heart stimulator for determining evoked response in the presence of polarization, said heart stimulator comprising a pulse generator devised for producing stimulation pulses of varying amplitudes, and a lead being intended to be introduced into the heart of a patient and connected to the pulse generator for delivering stimulation pulses to the heart, said evoked response detector comprising measuring and memory means for measuring and storing the electrode signal picked up by the lead in response to delivered stimulation pulses, at least one of said stimulation pulses having a sufficiently high amplitude for obtaining capture. The invention also relates to such a heart stimulator.

Background Art

To reduce the energy consumption of heart stimulators a so called AUTOCAPTURE™ function is used to maintain the energy of the stimulation pulses at a level just above that which is needed to effectuate capture, cf. e.g. US-A-5,458,623. A reliable detection of the evoked response, which then is necessary, is, however, not a simple matter, especially when it is desired to sense the evoked response with the same electrode as the one delivering the stimulation pulse. The reason therefore resides in the fact that the evoked response potential is small in amplitude compared to the residual polarization charge. The residual charge decays exponentially but tends to dominate the evoked potential for several hundreds of milliseconds after the stimulation. If the polarization is too high, it could be wrongly interpreted by the evoked response detector as a capture, i.e. contraction of the heart. The AUTOCAPTURE™ algorithm could then by mistake adjust the output amplitude of the stimulation pulse to a value below the actual capture level, which will result in no capture. If the electrode surface of the used electrode lead has significant polarization this could consequently disturb the AUTOCAPTURE™ function and result in loss of capture. To guarantee a safe and reliable detection of evoked response it is thus desirable to use leads having electrode surfaces with low polarization.

Several attempts have been made to solve the lead polarization problems in connection with evoked response detection. Thus US-A-5,417,718 discloses a system for maintaining capture wherein electrical post-stimulus signal of the heart, following delivery of a stimulation pulse, is compared to a polarization template, determined during a capture verification test. A prescribed difference between the polarization template and the post-stimulus signal indicates capture. Otherwise loss of capture is presumed and the stimulation energy is increased a predetermined amount to obtain capture.

A device according to the preamble of claim 1 is known from US-A-5 350 410.

There is mostly at least one significant slope in the bipolar measured IEGM signal, which makes it possible to discriminate the evoked response signal from slowly varying signals such as polarization signals. Thus in US-A-5,431,693 a method of verifying capture of the heart by a cardiac pacemaker is described. Observing that the non-capture potential is exponential in form and the evoked capture potential, while generally exponential in form, has one or more small-amplitude perturbations superimposed on the exponential wave form. These perturbations are enhanced for ease of detection by processing the wave form signal by differentiation to form the second derivative of the evoked response signal for analysis for the evoked response detection.

Unipolar detection of evoked response signals is however not possible by this technique. Abrupt slope changes or superimposed small-amplitude perturbations are levelled out if the measurements are made over a longer distance from the electrode to the stimulator casing.

Experiments have now shown that the evoked response signal amplitude is fairly constant, independent of the stimulation pulse amplitude, i.e. the evoked response signal amplitude does not vary with the amplitude of the stimulation pulse (provided that the stimulation amplitude is above the capture threshold). Further, it has been found that the electrode polarization is approximately linearly dependent on the stimulation pulse amplitude for a constant pulse duration. Experimental results are presented in greater detail below in connection with the description of fig. 1-3.

The purpose of the present invention is to provide an improved detector for determining evoked response based on the above discoveries, which can be used not only in a bipolar mode of operation but also in unipolar mode.

Disclosure of the Invention

This purpose is obtained with an evoked response detector according to the introductory portion of the description having the characterizing features of claim 1.

The detector according to the invention can be used also for unipolar detection of evoked response, which is an important advantage since unipolar leads are less complicated to manufacture and have longer working life than bipolar electrodes. In addition there is a desire to extend the use of heart stimulators, like pacemakers with AUTOCAPTURE™ function, also to patients with chronic unipolar leads. Another advantage of the detector according to the invention is that no extra stimulation pulse, resulting in extended current draining, is needed for measuring the polarization as in previously known technique, where stimulations and measurement of polarization are performed in the refractory period of the heart. Further, no extra test is required for tuning the sensitivity of the evoked response detector, contrary to the situation in prior art pacemakers, in which separate tests are used to find evoked response, polarization and capture threshold levels.

Thus, with the detector according to the invention, the cardiac signal is measured and stored at two different stimulation voltages, at least one of which being sufficient for giving capture. From these stimulation voltages and the resulting measured electrode signals, polarization signal level, evoked response signal level and capture threshold level can be calculated as will be described more in detail below. As mentioned above an important advantage compared to prior art methods is consequently that no stimulation is required in the refractory period of the heart for determining the electrode polarization level.

According to an advantageous embodiment of the device according to the invention, said evoked response detector comprises an averaging means for forming an average value of electrode signals picked up by the electrode lead in an evoked response window in response to each stimulation pulse of a plurality of delivered stimulation pulses of constant amplitude. In this way small variations in the measured evoked response and polarization signals are suppressed.

According to yet another advantageous embodiment of the detector according to the invention said evoked response detector comprises timing means for automatically initiating at regular time intervals a check and, when necessary, adjustment of the sensitivity threshold of the detector, said threshold sensitivity being defined as Pol_x + ER = U_xmeas, where Pol_x and U_xmeas designate the polarisation and the measured electrode signal respectively resulting from the stimulation pulse having the amplitude U_xstim. In this way it is possible to automatically adapt the evoked response sensitivity threshold to changes in the polarization and the evoked response signal without the pacemaker programmer being present.

According to still another advantageous embodiment of the detector according to the invention an integrating means is provided for integrating the picked up electrode signal within a programmable portion of the evoked response window. Electromagnetic interference and other periodic interference signals are then suppressed.

According to another aspect of the invention a heart stimulator is provided comprising the device for determining capture stimulation level, preferably for realizing an AUTOCAPTURE™ function.

Brief Description of the Drawings

To explain the invention more in detail as examples chosen embodiments of the detector according to the invention will now be described with reference to the drawings, on which <ul id="ul0001" list-style="none" compact="compact"><li>Fig. 1 shows the electrode signal (IEGM) for four different stimulation pulse amplitudes as a function of time from immediately after the stimulation complex is delivered, sample 0, to approximately 40 msec after the stimulation complex, sample 40,</li><li>Fig. 2 shows the "real" or "clean" evoked response signal as a function of time calculated from the measured signals in fig. 1,</li><li>Fig. 3 shows the polarization signals as a function of time calculated from the measured electrode signals in fig. 1,</li><li>Fig. 4 is a block diagram of the principal layout of the detector according to the invention,</li><li>Fig. 5 is a circuit diagram of the output stage of a pacemaker into which a detector according to the invention can be implemented,</li><li>Fig. 6 is a block diagram of an embodiment of the evoked response detector according to the invention, and</li><li>Fig. 7 is a block diagram of the evoked response detector according to the invention implemented in so called switch capacitor technique.</li></ul>

Description of Preferred Embodiments

The polarization of the pacemaker electrode can be described as<maths id="math0001" num="(1)"><math display="block"><mrow><mtext>Pol = </mtext><mfrac><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>stim</mtext></mrow></msub></mrow><mrow><mtext>α</mtext></mrow></mfrac><msub><mrow><mtext> * f(dur; RC</mtext></mrow><mrow><mtext>output</mtext></mrow></msub><mtext>)</mtext></mrow></math><img file="EP0906768B1_D0001.tif" /></maths> where Pol designates the polarization signal, U_stim the pacemaker stimulation pulse amplitude, α is a constant, dur designates the duration of the stimulation pulse and RC_output is the time constant of the pacemaker output lead system, see Konrad Mund, "Analysis of the polarization and the sensing behavior of electrodes for cardiac pacemakers", Pacemaker leads, pp. 503-509, Elsevier Science Publishers BV, 1991.

Thus, according to equation (1) above the polarization is a function of the duration dur of the stimulation pulse and the time constant RC_output. This means that if the duration dur of the stimulation pulse and the time constant RC_output are constant for different stimulation pulse amplitudes the polarization Pol is only depending on the stimulation pulse amplitude U_stim and this dependency is linear.

Studies on animals show that the evoked response signal amplitude ER is fairly constant for different stimulation pulse amplitudes U_stim and independent of the stimulation pulse duration dur. In view thereof the following relations are valid.<maths id="math0002" num="(2)"><math display="block"><mrow><msub><mrow><mtext>Pol</mtext></mrow><mrow><mtext>1</mtext></mrow></msub><msub><mrow><mtext> + ER = U</mtext></mrow><mrow><mtext>1meas</mtext></mrow></msub></mrow></math><img file="EP0906768B1_D0002.tif" /></maths><maths id="math0003" num="(3)"><math display="block"><mrow><msub><mrow><mtext>Pol</mtext></mrow><mrow><mtext>2</mtext></mrow></msub><msub><mrow><mtext> + ER = U</mtext></mrow><mrow><mtext>2meas</mtext></mrow></msub></mrow></math><img file="EP0906768B1_D0003.tif" /></maths><maths id="math0004" num="(4)"><math display="block"><mrow><msub><mrow><mtext>Pol</mtext></mrow><mrow><mtext>2</mtext></mrow></msub><mtext> = </mtext><mfrac><mrow><msub><mrow><mtext>Pol</mtext></mrow><mrow><mtext>1</mtext></mrow></msub></mrow><mrow><mtext>k</mtext></mrow></mfrac></mrow></math><img file="EP0906768B1_D0004.tif" /></maths> where<maths id="math0005" num="(5)"><math display="block"><mrow><mtext>k = </mtext><mfrac><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>1stim</mtext></mrow></msub></mrow><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>2stim</mtext></mrow></msub></mrow></mfrac></mrow></math><img file="EP0906768B1_D0005.tif" /></maths>

<i>U</i>_<i>1stim</i> designates a stimulation pulse amplitude which is supposed to be higher than U_2stim and high enough for producing capture. U_1meas designates the measured electrode signal consisting of the measured evoked response signal amplitude ER + possible polarization signal Pol₁ for the stimulation pulse amplitude U_1stim and U_2meas is the measured evoked response signal amplitude ER + possible polarization signal Pol₂ for the stimulation pulse amplitude U_2stim.

From the equations above the evoked response signal amplitude ER can be determined as<maths id="math0006" num="(6)"><math display="block"><mrow><mtext>ER = </mtext><mfrac><mrow><msub><mrow><mtext>(k * U</mtext></mrow><mrow><mtext>2meas</mtext></mrow></msub><msub><mrow><mtext>) - U</mtext></mrow><mrow><mtext>meas</mtext></mrow></msub></mrow><mrow><mtext>k - 1</mtext></mrow></mfrac></mrow></math><img file="EP0906768B1_D0006.tif" /></maths> where<maths id="math0007" num="(7)"><math display="block"><mrow><mtext>k = </mtext><mfrac><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>1stim</mtext></mrow></msub></mrow><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>2stim</mtext></mrow></msub></mrow></mfrac></mrow></math><img file="EP0906768B1_D0007.tif" /></maths>

The loss of capture level is given by the relation<maths id="math0008" num="(8)"><math display="block"><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>2meas</mtext></mrow></msub><mtext> = </mtext><mfrac><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>1meas</mtext></mrow></msub><mtext> - ER</mtext></mrow><mrow><mtext>k</mtext></mrow></mfrac></mrow></math><img file="EP0906768B1_D0008.tif" /></maths> which is obtained by putting ER equal to zero in equation (3) above, i.e. Pol₂ = U_2meas, if U_2stim results in loss of capture.

The capture threshold level is then equal to the one step higher stimulation pulse amplitude.

In practice the capture threshold level is determined as follows. To start with, stimulation is performed with a pulse amplitude that gives highest available probability for capture, preferably with the highest output pulse amplitude (typically 4.5V). The electrode signal which consists of the evoked response signal and polarization signal, is measured during a predetermined evoked response window after stimulation and the signal is stored. These steps are preferably repeated one to five times at the programmed stimulation pulse amplitude and an average of the measured electrode signals is calculated in order to suppress small variations in the measured evoked response and polarization signals.

After this formation of an average value the procedure above is repeated for successively decreasing stimulation pulse amplitudes till the loss of capture stimulation amplitude is found, given by equation (8) above.

The evoked response signal is calculated from equation (6) above. The most reliable result is obtained by using measured electrode signals for the highest stimulation pulse amplitude and a lower one. Also measured electrode signals for lower stimulation pulse amplitudes can be used as long as the stimulation pulse amplitudes are above the stimulation threshold.

The polarization signal can then be calculated for a certain stimulation pulse amplitude from equations (2) and (3). The polarization signal can be calculated for stimulation pulse amplitudes both above and below the stimulation threshold, for stimulation pulse amplitudes below the stimulation thresholds the evoked response signal being equal to zero.

If one polarization signal Poll is known it is then possible to calculate the polarization signal Pol₂ for a following specific pulse amplitude by using the equations (4) and (5).

By using the equations above it is also possible to determine the evoked response detector sensitivity. This could be done in two ways, one of which according to the relation<maths id="math0009" num=""><math display="block"><mrow><msub><mrow><mtext>sensitivity threshold = Pol</mtext></mrow><mrow><mtext>x</mtext></mrow></msub><msub><mrow><mtext> + ER = U</mtext></mrow><mrow><mtext>xmeas</mtext></mrow></msub></mrow></math><img file="EP0906768B1_D0009.tif" /></maths> where x indicates the order of the present stimulation. This means that a unique sensitivity has to be programmed for each stimulation pulse amplitude if polarization is present.

The other possibility of determining the detector sensibility is to subtract the calculated polarization signals for the actual stimulation pulse amplitude from the measured electrode signal. This will give the evoked response signal level which is equal to the sensitivity threshold.

Both the above described alternatives for determining the detector sensitivity requires stored values of the calculated evoked response signal and of the calculated polarization signal to correctly calculate the sensitivity threshold for each stimulation pulse amplitude.

Since the algorithm of the detector according to the invention can be integrated into the threshold search algorithm, no extra test is required for tuning the sensitivity of the evoked response detector, contrary to what is needed in prior art pacemakers, in which separate tests are used to find evoked response, polarization and threshold levels.

Fig. 1 shows the electrode signal (IEGM) for different stimulation amplitudes as a function of time. Thus the electrode signals are recorded from immediately after the stimulation complex is delivered, sample 0, and until approximately 40 msec after the stimulation, sample 40. Curve A is obtained for a stimulation pulse amplitude of 0.6 V, curve B is obtained for a stimulation pulse amplitude of 1.5 V, curve C is obtained for a stimulation pulse amplitude of 3.0 V, and curve D for a stimulation pulse amplitude of 4.5 V. All curves A-D are averaged from five measurements.

Each curve represents the sum of the evoked response signal and the polarization signal. As the evoked response signal is essentially constant it is apparent from the figure that the polarization signal varies significantly with the used stimulation pulse amplitude, the shown maximum variation amounting to approximately 50 mV.

With the aid of equation (6) above the "real" or "clean" evoked response signals, without polarization signal can be calculated from the data in fig. 1, and in fig. 2 these calculated evoked response signals are shown as a function of time for all possible stimulation amplitude combinations, namely<maths id="math0010" num=""><math display="block"><mrow><mtext>k = </mtext><mfrac><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>1stim</mtext></mrow></msub></mrow><mrow><msub><mrow><mtext>U</mtext></mrow><mrow><mtext>2stim</mtext></mrow></msub></mrow></mfrac><mtext> =</mtext><mspace linebreak="newline" /><mtext> = 4.5/3, 4.5/1.5, 4.5/0.6, 3.0/1.5, 3.0/0.6, and 1.5/0.6.</mtext></mrow></math><img file="EP0906768B1_D0010.tif" /></maths> The lowest curve in fig. 2 is obtained for K = 4.5/3 and this curve is shifted away from the others for some reason unknown to us.

In fig. 3 the polarization signals for corresponding stimulation pulse amplitudes are shown. These polarization signals are calculated by the relation<maths id="math0011" num=""><math display="block"><mrow><msub><mrow><mtext>Pol = U</mtext></mrow><mrow><mtext>xmeas</mtext></mrow></msub><msub><mrow><mtext> - ER</mtext></mrow><mrow><mtext>ave</mtext></mrow></msub></mrow></math><img file="EP0906768B1_D0011.tif" /></maths> where ER_ave denotes the average curve of the calculated "real" evoked response signals shown in Fig. 2. The curves marked by A, B, C and D correspond to the curves A,B,C,D respectively in fig. 1.

Fig. 4 shows a block diagram of the principal layout of the detector according to the invention incorporated in a heart stimulator. The stimulator comprises a pulse generator 2 which through a lead 6 is connected to the heart 8 of a patient. The pulse generator 2 is devised to produce stimulation pulses of varying amplitudes which through the lead 6 are transferred to the heart 8. The evoked response detector 4 is also connected to the lead 6. The evoked response detector 4 comprises a highpass filter 10 for eliminating the DC level in the electrode signal picked up by the lead 6. The filter cut-off frequency should be low enough to not distort the low frequency content of the electrode signal, preferably 1 Hz or lower.

The highpass filtered electrode signal is supplied to an integrating means 16 (see below and to analyzing means 12 for determining the capture stimulation level from a predetermined relation between the amplitudes of at least two stimulation pulses of different amplitudes and the resulting measured electrode signals, as described above.

The highpass filter 10 is disconnected by the switch 11 from the lead 6 during stimulation. As a consequence the electrode signal obtained before the stimulation in question will be stored in the filter 10. When the evoked response detector is enabled after a stimulation the difference between the electrode signal before stimulation and after is supplied to the analyzing means 12.

Timing means 14 are provided for determining an ER-window during which the electrode signal is measured and stored. This ER-window normally extends from 0 to 62.5 msec after stimulation.

To suppress electromagnetic interference and other periodic interference signals an integrating means 16 can be provided to integrate the electrode signal from the beginning of the evoked response or ER-window to normally 40 msec. The exact duration of the integration time and the start of the integration in the ER-window is programmable.

As an alternative an averaging means 18 can be provided for forming the average value of a predetermined number of measured electrode signals.

When the detector according to the invention is implemented in a pacemaker special measures have to be taken for obtaining correct measurements when activating the evoked response detector in the ER-window.

Fig. 5 is a circuit diagram of the output stage of a pacemaker. In this output stage the output capacitor C_stim is always empty before stimulation, otherwise the output amplitude will be undesirably low. Before stimulation, capacitor C_res is charged to the desired stimulation voltage, V_stim. When stimulating the following happens:

The switches S2, S3, and S4 are opened. The switch S1 is closed and the capacitor C_stim is thereby charged by capacitor C_res. A current is now flowing through the patient load represented by the resistor R_patient and the resulting voltage drop generates a stimulation pulse. After approximately 1 msec the stimulation is terminated and the switch S1 is opened and the switch S2 is closed, which results in a fast discharge of the capacitor C_stim. After about 6 msec the fast discharge is terminated and the switch S2 is opened. The switch S3 is then closed and in this way a slowly discharging resistor R_slow of about 25 kohm is connected. After another 6 msec the evoked response detector is activated. If the fast discharge was not performed a considerably higher current should have passed through the resistor R_patient when connecting the resistor R_slow, which would result in disturbances during the evoked response detection. Thus the slowly discharging resistor R_slow in the pacemaker output stage should not be connected during the ER-window as it could disturb the electrode signal.

Fig. 6 shows in more detail one embodiment of the evoked response detector according to the invention. The heart electrode signal picked up by the lead 6 in fig. 4 is then supplied to a highpass filter 20. An amplifier 22 and an A/D converter 24 are provided for amplifying and A/D converting respectively the filtered signal. The block 26 comprises a digital signal processor for calculating the evoked response signal according to equation (6) above and comparing the calculated ER-value with a predetermined reference value to determine whether evoked response is detected or not.

Thus in the embodiment shown in fig. 6 the algorithm for determining whether an evoked response is detected or not is implemented in software by use of a microprocessor. Instead of a microprocessor this algorithm can also be implemented in random logic, which means realization by ordinary logic element, that is logic gates.

The detector according to the invention can also be implemented in the pacemaker electronics by use of switch capacitor (SC) technique. The algorithm is then implemented in SC technique, where different capacitors serve as memory elements for storing the different electrode potentials and SC-adding, subtracting and multiplying circuits are used for performing the necessary calculations as explained above.

Fig. 7 shows a block diagram of an embodiment of the evoked response detector according to the invention implemented in such switch capacitor technique. The heart electrode signal, picked up by the lead 6 in fig. 4 is supplied to a highpass filter 28. The filtered signal resulting from a stimulation with a pulse amplitude of U_1stim is supplied to a SC storage/amplifier 32 and the resulting output signal U_1meas is delivered to a SC subtractor 34.

The filtered electrode signal resulting from stimulation with the pulse amplitude U_2stim is supplied to a SC multiplier/amplifier 30 together with the constant k according to equation (5) above, and the output signal k*U_2meas is delivered to the SC subtractor 34, too. In the subtractor/divider 34 ER = (k*U_2meas-U_1meas)/k-1 is formed and supplied to a SC comparator 36 and compared with a reference voltage V_ref for determining whether an evoked response is detected or not. The signal "ER-detection yes/no" is then transferred to the logic unit of the pacemaker for controlling the pacemaker.

When implementing the detector according to the invention in a pacemaker electronics, this can be done by modifying the automatic threshold search algorithm that is normally used. The threshold search is normally done every 8 hours and should then be modified to stimulate several times for every stimulation pulse amplitude to make it possible to take the average value over several measured evoked response and polarization signals. Automatic measurement of the evoked response signal every 8 hour also makes it possible to automatically adapt the evoked response sensitivity threshold to changes in the polarization and evoked response signal without a pacemaker programmer present.

The detector according to the invention can, however, also be implemented into the pacemaker programmer to determine the evoked response signal level, polarization value and capture threshold level at implantation of the pacemaker.

The detector according to the invention can also be used for automatic adjustment of the output stage fast discharge time to minimize the electrode polarization voltage, cf. fig. 5 above.