2. Description of the prior art Most heart stimulating devices, or pacers, are arranged to stimulate the right ventricle of the heart. It is also known to stimulate the left ventricle. In particular for the treatment of congestive heart failure (CHF) or other severe cardiac failures, it is known to stimulate the left ventricle, or both ventricles, in order to optimise the hemody- namic performance of the heart.

US-A-5 720 768 describes different possible electrode positions in order to stimulate or sense the different chambers of the heart.

In different kinds of heart stimulating devices it is also known to use an impedance value in order to control different pacing parameters.

US-5-154 171 describes the use of impedance values to control the pacing rate. The pacer described in this document is only arranged to stimulate the right side of the heart.

US-A-6 070 100 describes that electrodes may be positioned in both the left and the right atrium as well in the left and the right ventricle. The document describes the possibility of sensing the im-

pedance between different electrodes. The sensed impedance val- ues may be used to improve the cardiac output.

US 2001/0012953 A1 describes bi-ventricular pacing. An imped- ance may be measured between electrodes on the right and the left sides of the heart. The variation of the impedance with time is de- tected. The detected impedance variation may be used in order to synchronise the contraction of the ventricles.

US 2001/0021864 A1 describes different manners of using the proximal and distal electrodes of different leads in order to inject a current and to measure an impedance. The measured impedance value may be used in order to maximise the cardiac flow.

For a patient suffering from congestive heart failure (CHF) it is of a great benefit to be able to increase the cardiac output, thereby de- creasing the degree of CHF. One cause of CHF is that the left and right ventricles are not synchronised with each other. By optimising the synchronisation between the ventricles, the filling of the ventri- cles and the cardiac output may be increased.

SUMMARY OF THE INVENTION A purpose of the present invention is to provide an implantable heart stimulating device which is able to deliver stimulating pulses to both the ventricles of a heart and which is able to control the de- livery of the stimulating pulses such that the cardiac output is im- proved. A further purpose is to provide such a device which uses an impedance measurement in order to control the delivery of the stimulating pulses. A further purpose is to provide such a device which is able to improve the heart condition for a patient suffering from CHF. A still further purpose is to provide such a device which automatically finds an optimal time interval between stimulating pulses to the two ventricles. Another purpose is to provide such a device which in a relatively simple manner is able to automatically deliver the stimulating pulses in an optimal way. According to the

invention, also a system including such a device and a manner of using the system are provided.

The above purposes are achieved by an implantable heart stimu- lating device comprising: a housing a control circuit arranged in said housing, the control circuit being adapted to be connected to a first electrode to be positioned to stimulate a first ventricle of the heart, said control circuit also being adapted to be connected to at least a second electrode to be positioned to stimulate the second ventricle of the heart, said control circuit being arranged to at least enable the fol- lowing : a) delivering electrical stimulating pulses to said first and second electrodes in order to stimulate the first and second ventricles, respectively, the control circuit being arranged to enable the delivery of the said stimulating pulses to said first and second electrodes within the same cycle of the heart such that there is a time interval (AT) between them, the control circuit being ar- ranged such that said time interval (AT) is variable, b) sensing signals receivable from electrodes positionable at two different positions in the heart, c) deriving an impedance value based on said sensed signals, said impedance value being indicative of the impedance be- tween said electrodes positionable at two different positions in the heart, d) determining a minimum value and a maximum value of said im- pedance value during a heart cycle, e) determining a relationship between said minimum and maximum valu es, f) varying said time interval (AT) and monitoring said relationship over a plurality of heart cycles, g) setting said time interval (AT) such that said relationship fulfils a predetermined requirement.

It should be noted that the time interval (AT) may also be chosen to be equal to zero, i. e. in this case stimulation signals are delivered simultaneously to the first and second electrodes. Furthermore, it should be noted that the time interval (AT) may be positive or nega- tive, i. e. the first electrode may emit stimulating pulses before or after the second electrode. In a practical use of the device, the sensed signals may be derived from electrodes positioned on dif- ferent sides of the left ventricle. By monitoring the impedance value between such electrodes, an indication of the volume of blood in the left ventricle may be obtained. Said minimum and maximum values depend on the maximum and minimum, respectively, of the amount of blood in the ventricle. By determining said relationship and by setting the time interval (AT) such that the relationship fulfils a pre- determined requirement, the delivery of the stimulating pulses to the first and second electrodes can be optimised in order to improve the cardiac output. In this manner, for example the heart condition of a patient suffering from CHF may be improved.

According to a preferred embodiment of the invention, said control circuit is arranged such that said relationship comprises the ratio between said minimum value and said maximum value. If the elec- trodes between which the impedance value is derived are suitably positioned, said ratio is closely linked to the so-called ejection frac- tion (EF). It has been found to be advantageous to use this ratio for controlling the delivery of the stimulating pulses.

According to another embodiment of the invention, said control cir- cuit is arranged such that said relationship comprises the difference between said minimum value and said maximum value. Also this difference can function as an indication of the cardiac output and may therefore also be advantageously used for controlling the de- livery of the stimulating pulses.

According to a further embodiment of the invention, said control cir- cuit is arranged such that said relationship comprises the ratio be- tween said minimum value and the difference between said mini- mum value and said maximum value. This particular ratio is even

closer linked to the EF if the electrodes between which the imped- ance value is derived are suitably positioned in relation to the heart.

It should be noted that preferably, the ratio here refers to the abso- lute value of the division between the minimum value and said dif- ference, since if the difference is negative the ratio would otherwise be negative. It is therefore preferably the magnitude of the ratio which is being referred to.

According to a further embodiment of the invention, said predeter- mined requirement is that said ratio is minimized. By minimising the ratio it has been found that an optimal cardiac output can be achieved. It should be noted that minimising the ratio is of course the same as maximising the inverse of the ratio. This possibility is thus included in the definition of minimising the ratio in this docu- ment.

According to still a further embodiment of the invention, said control circuit is arranged such that said time interval (AT) is changed in a first direction, said first direction being either an increase or a de- crease of said time interval (AT), wherein the control circuit is ar- ranged to monitor the change of said ratio when said time interval (AT) is changed in said first direction, wherein, if said ratio de- creases, said time interval is further changed in said first direction until said predetermined requirement has been established. This has been found to be an advantageous embodiment for finding the time interval (AT) at which the predetermined requirement is ful- filled. For example, in this manner the minimum of the mentioned ratio may be established.

According to a further embodiment of the invention, the control cir- cuit is arranged such that if said ratio increases, said time interval is changed in the opposite direction to said first direction, whereaf- ter said time interval is further changed in said opposite direction until said predetermined requirement has been established.

Through this embodiment, it is established that the time interval is changed in the correct direction such that the predetermined re- quirement may be established in an efficient manner.

According to still another embodiment of the invention, said control circuit is arranged also to enable the reception of signals indicating the activity level of a living being into which the heart stimulating device is implanted, wherein the control circuit is arranged such that at least the steps f) and g) are performed at a time when said sig- nals indicate a low level of activity. Preferably, the optimal time in- terval (AT) is thus established while the patient in question is at rest. This is made possible by this embodiment, according to which the control circuit is also able to detect the level of activity of the living being in question.

According to a further embodiment of the invention, said control cir- cuit is arranged to enable the delivery of stimulating pulses in which at least one atrio-ventricular delay (AV) is controllable, wherein said control circuit is arranged to keep said time interval (AT) at said set value and to: h) vary said atrio-ventricular delay (AV) and to thereby monitor said relationship over a plurality of heart cycles, i) set said atrio-ventricular delay (AV) such that said relationship fulfils said predetermined requirement. Since the device is ar- ranged in this manner, the output of a heart can be further im- proved.

According to another embodiment of the invention, the heart stimu- lating device is arranged such that said control circuit is arranged to be connected to a first lead comprising said first electrode and a second lead comprising said second electrode, wherein said control circuit is arranged such that said sensed signals, receivable from electrodes positioned at two different positions, are received via said first and second leads, respectively. The heart stimulating de- vice may thus for example be provided with a connector portion via which the control circuit may be connected to two different leads.

Such leads may be positioned at different positions in relation to the heart. It is thereby possible to derive the impedance value between selected positions.

The above objects of the invention are also achieved by a heart stimulating system comprising a heart stimulating device according to any of the preceding embodiments and a first lead comprising at least said first electrode and a second lead comprising at least said second electrode, wherein said first and second leads are con- nected to the heart stimulating device such that said first and sec- ond electrodes are connected to said control circuit. The system thus comprises the two leads connected to the heart stimulating de- vice. With such a system the above mentioned advantages may be achieved.

According to a preferred embodiment of said system, the system is arranged such that said impedance value is sensed between an electrode of said first lead and an electrode of said second lead.

The leads may be positioned at suitable positions in relation to the heart. A suitable impedance value may thereby be derived between electrodes of the first and second lead, respectively.

The objects of the invention are also achieved by a manner of using a heart stimulating system according to any of the above embodi- ments, wherein said first electrode is positioned to stimulate a first ventricle of a heart of a human or animal being and said second electrode is positioned to stimulate the second ventricle of said heart and wherein the steps a) to g) are performed. According to this manner, the device is thus actually used to stimulate the two ventricles of a heart. Through this manner, the advantages de- scribed above in connection with the device may be achieved.

According to a preferred manner of using the system, said imped- ance value is sensed between two electrodes positioned such that the impedance value is measured across at least a part of one of said first and second ventricles. Through this manner of using the system, an indication of the amount of blood in the ventricle may be derived by said impedance value. The variation of this impedance value may be used as an indication of the amount of blood pumped by the ventricle.

According to a preferred manner of using the system, said ventricle, across which the impedance value is measured, is the left ventricle of the heart. To monitor the ejection fraction of the left ventricle is particularly important when for example treating a patient suffering from CHF.

According to a further manner of using the system, an impedance value is sensed across at least a part of the left atrium of said heart. Also the variation in the amount of blood in the left atrium may be used to control the heart stimulating device.

BRIEF DESCRIPTION OF THE DRAWINGS Fig 1 shows schematically a heart stimulating device connected to leads with electrodes positioned in a heart.

Fig 2 shows a flow chart of the function of the heart stimulating de- vice according to one embodiment.

Fig 3 shows schematically the variation of the impedance with time.

Fig 4 shows schematically how a relationship between Zmin and Zmax depends on a time interval AT.

Fig 5 shows a flow chart of the function of the heart stimulating de- vice according to an embodiment for adjusting the AV-delay.

DESCRIPTION OF PREFERRED EMBODIMENTS An embodiment of the invention will now first be described with ref- erence to Fig 1. Fig 1 thus schematically shows an implantable heart stimulating device 10. The heart stimulating device 10 is hereinafter also called a pacer. Such a heart stimulating device 10 is well known to a person skilled in the art and will therefore not be described in all its details here. The pacer 10 comprises a housing 12. A control circuit 14 is arranged in the housing 12. The pacer 10

includes a connector portion 16 to which a plurality of leads 30,40, 50,60 may be attached.

A first lead 30 comprises a distal electrode 31 (also called tip elec- trode) and a proximal electrode 32 (also called ring electrode). In the shown embodiment the lead 30 is thus bipolar. However, it is also possible that one or more leads are unpolar, i. e. that it only comprises one electrode. The lead 30 includes electrical conductors (not shown) through which the electrodes 31,32 are connected to the control circuit 14. The control circuit 14 is also adapted to be connected to a second lead 40, which has corresponding electrode surfaces 41,42.

The pacer 10 may also be arranged such that it is connectable to further leads. Fig 1 shows a third lead 50 with electrode surfaces 51,52 and a fourth lead 60 with electrode surfaces 61,62.

The control circuit 14 is arranged to emit stimulating pulses to dif- ferent electrodes and also to sense signals received from the elec- trodes. The manner of arranging the control circuit 14 in order to perform the emission of pulses and the sensing is known to a per- son skilled in the art and will therefore not be shown in more detail here.

Fig 1 also schematically shows a heart comprising a right atrium RA, a right ventricle RV, a left atrium LA and a left ventricle LV. In the illustrated embodiment the electrodes 31,32 are positioned in a conventional manner near the apex of the right ventricle RV. The lead 40 is positioned such that the electrodes 41,42 may be used for emitting stimulating pulses to the left ventricle LV. The lead 40 may for example be introduced through the right atrium RA, via the coronary sinus into the middle or great cardiac vein. In the shown embodiment a third lead 50 is introduced such that the electrodes 51,52 are positioned in the coronary sinus, a fourth lead 60 is in- troduced such that the electrodes 61,62 are positioned in the right atrium RA in a conventional manner.

The control circuit 14 is arranged such that it may deliver stimulat- ing pulses to both ventricles RV, LV, for example to the electrodes 31 and 41. The control circuit 14 is thus arranged such that stimu- lating pulses to the electrodes 31,41 may be delivered within the same cycle of the heart (within the same heartbeat) with a time in- terval AT between the pulses to the electrodes 31 and 41. The con- trol circuit 14 is arranged such that this time interval AT is variable.

The time interval AT is sometimes also called the VV-interval. The control circuit 14 is also arranged such that it may sense signals receivable from the different electrodes and such that an impedance value Z is derived based on sensed signals, the impedance value Z being indicative of the impedance between electrodes at two differ- ent positions of the heart. For example, the impedance may be measured between the electrodes 31,32 of the first lead 30 and the electrodes 41,42 of the second lead 40. The impedance value Z may be derived in different manners described in for example the above cited documents. According to a preferred embodiment, a current is injected between electrodes 31 and 41 and the imped- ance value is measured between the ring electrodes 32,42. It should be noted that it is also possible to derive an impedance value Z between other electrodes, for example between the elec- trodes 31,32 of the first lead 30 and the electrodes 51,52 of the third lead 50. Another possible impedance value is the impedance between the electrodes 51,52 of the third lead 50 and the elec- trodes 61,62 of the fourth lead 60.

The control circuit 14 is arranged such that it can determine a minimum value Zmin and a maximum value Zmax of the impedance during a heart cycle. Furthermore, the control circuit 14 is arranged to determine a relationship between Zmin and Zmax. The control cir- cuit 14 is also arranged to vary the time interval AT and to monitor the relationship over a plurality of heart cycles. Moreover, the con- trol circuit 14 is arranged to set the time interval AT such that the relationship fulfils a predetermined requirement.

The pacer 10 may also be arranged to receive signals indicating the activity level of a living being into which the heart stimulating device 10 is implanted. Such signals can for example be produced by an activity sensor 18 included within the housing 12. Different kinds of activity sensors 18 are known to a person skilled in the art. For ex- ample, such an activity sensor may sense the movement of the pacer 10 and thereby the movement of a being carrying the pacer 10. It is also possible to detect the activity of the patient by sensing signals received from different electrodes connected to the pacer 10.

The impedance Z measured between for example the electrodes 32 and 42 depends on the amount of blood in the left ventricle LV. As the amount of blood in the ventricle LV varies during a heart cycle, the measured impedance value Z also varies. Fig 3 illustrates schematically how the impedance value Z may vary with time t over a heart cycle HC. The impedance value Z is low when the ventricle LV is filled with blood. During the systolic phase, when the ventricle LV pumps out the blood, the impedance Z increases to a maximum value Zmax, whereafter the impedance value Z is lowered when the ventricle LV fills with blood during the diastolic phase. The control circuit 14 is thus arranged such that Zmin and Zmax during a heart cy- cle may be determined. By sensing events in the heart, the control circuit 14 can distinguish different heart cycles from each other.

The difference Zmin-Zmax is related to the stroke volume of the ven- tricle LV. The so-called ejection fraction EF is defined as the stroke volume divided by the end diastolic volume. The ejection fraction EF is thus related to (Zmin~ Zmax)/Zmin Preferably, we may define the ejection fraction EF as the absolute value in order to always get a value that is larger than zero. The ejection fraction EF is also re- lated to the value of Zmax/Zmin.

The control circuit is arranged to determine a relationship between Zmin and Zmax. This relationship can for example be any of the above-described relationships which relate to the stroke volume or the ejection fraction EF. One example of this relationship is the

value of Zmin/Zmax The control circuit can be arranged to determine the time interval AT such that the ratio Zmin/Zmax is minimised (or such that its inverse is maximised). The control circuit 14 is thus arranged to set the time interval AT such that a predetermined re- quirement is fulfilled. In this example, the predetermined require- ment is thus that Zmin/Zmax is minimised. By setting AT such that the predetermined requirement is fulfilled, the stroke volume, or the ejection fraction EF, is controlled to be as large as possible. The cardiac output is therefore improved. To improve the cardiac output in this manner is important for example for a patient suffering from CHF.

The flow chart of Fig 2 illustrates how the control circuit 14 may be arranged to operate. The flow chart starts by choosing a value for AT. This value may for example be a previously set value for AT or that AT = 0. Stimulating pulses are thereafter delivered to the elec- trodes (for example to the electrodes 31 and 41) with the time inter- val AT. The impedance value Z is sensed over at least a heart cy- cle. Zmin and Zmax are determined. In order to improve the measure- ment of Zmin and Zmax it is also possible to sense the impedance variation during several heart cycles before determining Zmin and Zmax. Zmin and Zmax may in this case be the average value of Zmin and Zmax, respectively, over several heart cycles.

Thereafter a relationship between Zmin and Zmax is determined. As pointed out above, this relationship may for example be Zmin/Zmax The value of the determined relationship is stored. A new value for AT is set and the previous steps are carried out again in order to determine a new relationship between Zmin and Zmax and to store also this relationship. The new value for AT may be chosen in dif- ferent manners. It is for example possible to change AT in a first direction, for example to increase AT with a small amount. The control circuit 14 may then be arranged to monitor whether the rela- tionship Zmin/Zmax increases or decreases. If this relationship de- creases, the time interval AT may be further increased and the steps are carried out again in order to determine another relation- ship between Zmin and Zmax. On the other hand, in case the ratio Zmin

/Zmax were to increase, the time interval AT may be changed in the other direction, i. e. according to this example AT would then be de- creased instead of increased. It should be noted that AT can even be negative if it is further decreased. Whether AT is positive or negative is thus decisive of which of the two ventricles is first stimulated. The loop illustrated in Fig 2 is carried out a sufficient number of times such that it is possible to determine a AT for which the ratio Zmin/Zmax is as low as possible.

In Fig 4 the ratio Zmin/Zmax as a function of AT is illustrated with a number of points. These points are thus obtained in the manner il- lustrated in Fig 2 by determining the relationship Zmin/Zmax for dif- ferent values of AT. The dots illustrated in Fig 4 define a curve in which a minimum can be established. This minimum is in the illus- trated figure obtained for AT = T1. The control circuit thus deter- mines that at AT = T1, the ratio Zmin/Zmax fulfils the predetermined requirement, i. e. in this example that the ratio is as small as possi- ble. When this has been decided, AT is set to be equal to T1. Ac- cording to a preferred embodiment, the steps illustrated in Fig 2 are carried out when the being into which the pacer 10 is implanted is at rest. This can for example be done at night when the person or animal in question is asleep. As stated above, the pacer 10 may detect the activity level. The control circuit 14 may thus be arranged such that the different steps are carried out when a signal indicates a low level of activity.

Once the time interval AT has been determined and set equal to T1, the control circuit 14 may be arranged to carry out a similar deter- mination in order to optimise a value for AV. AV is the so-called AV- delay. This is the time between an atrial sensed or paced event and the delivery of a ventricular output pulse. The AV-delay considered here may for example be the AV-delay for the right part of the heart.

As is shown in Fig 5, a certain value for AV is chosen. Thereafter stimulating pulses are delivered with this AV-delay and with the al- ready set time interval AT = T1. An impedance value Z is sensed.

This impedance value Z can be the same impedance value as illus- trated above. Zmin and Zmax are determined. A relationship between

Zmin and Zmax is also determined, for example any of the above mentioned relationships. This relationship is stored. A new AV- delay is chosen. This can be done for example in an analogous manner to that according to which the new AT was chosen above.

The previous steps are then carried out again and a new relation- ship is determined for the new AV-delay. The different stored rela- tionships are considered together with the corresponding AV- values. A value AV = AV 1 is determined such that the predeter- mined requirement is fulfilled, for example that the ratio Zmin/Zmax is as low as possible.

It is also possible to again perform the steps illustrated in Fig 2 to possibly set a new AT if this is necessary in order to further improve the cardiac output.

In the embodiment discussed above, the impedance value was sensed between electrodes 31,32 of the first lead and electrodes 41,42 of the second lead. However, it is also possible to sense other impedance values in the heart as for example illustrated in the above-disclosed documents. For example, it is possible to sense an impedance value between electrodes 51,52 of the third lead 50 and electrodes 61,62 of the fourth lead 60. Such an impedance value may be an indication of the amount of blood in the left atrium LA. It is also possible to use this impedance value in order to control the time interval AT and the time interval AV in the same manner as il- lustrated above.

The heart stimulating device 10 according to the invention thus comprises a housing 12 with the control circuit 14 described above.

However, the invention also relates to a heart stimulating system.

This system comprises the heart stimulating device 10 and at least a first lead 30 and a second lead 40 connected to the heart stimu- lating device 10 such that at least two electrodes 31,41 are con- nected to the control circuit 14. The system is preferably arranged such that the measured impedance value Z is sensed between an electrode 31 or 32 of the first lead 30 and an electrode 41 or 42 of the second lead 40.

The invention also relates to a manner of using such a heart stimu- lating system. According to this use, the first lead 30 is arranged such that the first electrode 31 and/or 32 is positioned to stimulate a first ventricle RV of a heart and the second lead 40 is arranged such that the second electrode 41 and/or 42 is positioned to stimu- late the second ventricle LV of the heart. According to his manner of using the device the above-illustrated steps are carried out.

The leads are preferably arranged such that the impedance value Z is measured across at least a part of one of said ventricles RV, LV, preferably across at least part of the left ventricle LV as has been discussed above. Alternatively, or additionally, electrodes 61,62 and 51,52 may be arranged such that an impedance value is sensed also across at least a part of the left atrium LA of the heart.

The invention is not limited to the described embodiments but may be varied and modified within the scope of the following claims.