Apparatus and method for controlling the delivery of contractility modulating non-excitatory signals to the heart

• US 6,360,126 B1
• Filed: 08/20/1999
• Issued: 03/19/2002
• Est. Priority Date: 08/20/1999
• Status: Expired due to Term

• Current Assignee: Impulse Dynamics NV
• Original Assignee: Impulse Dynamics NV
• Inventors: Mika, Yuval, Prutchi, David
• Primary Examiner(s): Layno, Carl
• Application Number:
  US09/378,776
• Time in Patent Office: 942 Days
• Field of Search: 607/4, 607/5, 607/9, 607/17
• US Class Current: 607/9
• CPC Class Codes: A61N 1/368 comprising more than one electrode co-operating with different heart regions A61N1/3622, A61N1/3627 take precedence

Abstract

Apparatus for automatically controlling the delivery of excitable tissue control signals to a heart. The apparatus includes an excitable tissue control unit for delivering excitable tissue control signals to the heart, an action potential duration (APD) determining unit for receiving sensed cardiac action potential related signals. The APD determining unit determines an estimated action potential duration value from one or more action potential related signals, computes one or more excitable tissue control signal parameters, and controls the delivery of excitable tissue control signals based on the computed signal parameter(s). The cardiac action potential related signals may be cardiac close bipolar electrogram signals and cardiac monophasic action potential signals. Methods are disclosed for use with the apparatus to control the delivery of excitable tissue control signals to the heart.

Claims

1. A method for automatically controlling the delivery of excitable tissue control signals to a heart of a patient, the method comprising the steps of:

determining an estimated action potential duration value from at least one cardiac action potential related signal sensed at a first cardiac site of said heart;

processing said estimated action potential duration value to obtain at least one excitable tissue control signal parameter; and

using said at least one parameter to control the delivery of one or more excitable tissue control signals to a second cardiac site of said heart after the time of occurrence of said at least one cardiac action potential related signal of said step of determining.

2. The method according to claim 1 wherein said at least one cardiac action potential related signal is a close bipolar electrogram signal.

3. The method according to claim 2 wherein said close bipolar electrogram signal includes a first signal component representing the differentiated upstroke of the fast depolarization phase of a cardiac action potential and a second signal component representing the differentiated fast repolarization phase of said cardiac action potential, and wherein said step of determining comprises the steps of:

determining a first time point at which the amplitude of said first signal component first crosses a first threshold value;

determining a second time point at which the amplitude of said second signal component first crosses a second threshold value; and

obtaining said estimated action potential duration value by determining the value of the time interval between said second time point and said first time point.

4. The method according to claim 3 wherein said close bipolar electrogram signal also includes a third signal component comprising an electrical artifact induced by the delivery of an excitable tissue control signal to said second cardiac site within the duration of said at least one cardiac action potential and wherein the method further comprises the step of processing said close bipolar electrogram signal to reduce or eliminate said third signal component.

5. The method according to claim 4 wherein said third signal component is reduced or eliminated by using a method selected from signal blanking and active signal canceling.

6. The method according to claim 3 wherein said first threshold value is a positive threshold value and said second threshold value is a negative threshold value.

7. The method according to claim 3 wherein said first threshold value is a negative threshold value and said second threshold value is a positive threshold value.

8. The method according to claim 2 wherein said close bipolar electrogram signal includes a first signal component representing the differentiated upstroke of the fast depolarization phase of a cardiac action potential and a second signal component representing the differentiated fast repolarization phase of said cardiac action potential, and wherein said step of determining comprises the steps of:

determining a first time point at which the amplitude of said first signal component first crosses a first threshold value going in a first direction;

determining a second time point at which the amplitude of said second signal component first crosses a second threshold value going in a second direction; and

obtaining said estimated action potential duration value by determining the value of the time interval between said second time point and said first time point.

9. The method according to claim 8 wherein said first threshold value is a positive threshold value, said first direction is a positive going direction, said second threshold value is a negative threshold value and said second direction is a negative going direction.

10. The method according to claim 8 wherein said first threshold value is a negative threshold value, said first direction is a negative going direction, said second threshold value is a positive threshold value and said second direction is a positive going direction.

11. The method according to claim 1 wherein said first cardiac site is in the vicinity of said second cardiac site.

12. The method according to claim 1 wherein said first cardiac site and said second cardiac site are located in or about the left ventricle of said heart.

13. The method according to claim 1 wherein said at least one cardiac action potential related signal is a monophasic action potential signal.

14. The method according to claim 13 wherein said monophasic action potential signal comprises a sharp leading edge related to the fast depolarization phase of a cardiac action potential and has a maximal amplitude value, and wherein said step of determining comprises the steps of:

determining a first time point at which the amplitude of said sharp leading edge first crosses a first threshold value;

determining said maximal amplitude value;

determining a second time point at which the amplitude value of said monophasic action potential signal is equal to a fraction of said maximal amplitude value; and

obtaining said estimated action potential duration value by determining the value of the time interval between said second time point and said first time point.

15. The method according to claim 14 wherein said monophasic action potential signal also comprises a artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to said second cardiac site within the duration of said at least one cardiac action potential, and wherein the method further comprises the step of processing said monophasic action potential signal to reduce or eliminate said artifact component.

16. The method according to claim 15 wherein said artifact component is reduced or eliminated by using a method selected from signal blanking and active signal canceling.

17. The method according to claim 13 wherein said monophasic action potential signal comprises a sharp leading edge related to the fast depolarization phase of a cardiac action potential and has a maximal amplitude value, and wherein said step of determining comprises the steps of:

high pass filtering said monophasic action potential signal to obtain a high pass filtered signal;

processing said high pass filtered signal to determine a first time point at which the amplitude of said high pass filtered signal first crosses a first threshold value;

low pass filtering said monophasic action potential signal to obtain a low pass filtered signal;

processing said low pass filtered signal to determine the maximal amplitude value thereof;

determining a second time point at which the amplitude value of said low pass filtered signal is equal to a fraction of said maximal amplitude value; and

obtaining said estimated action potential duration value by determining the value of the time interval between said second time point and said first time point.

18. The method according to claim 1 wherein said step of processing comprises computing from said estimated action potential duration value at least one excitable tissue control signal parameter selected from the delay between the detection of a cardiac action potential and the initiation of said excitable tissue control signal, the duration of said excitable tissue control signal, the intensity of said excitable tissue control signal, the waveform of said excitable tissue control signal, the polarity of said excitable tissue control signal and any combination thereof.

19. The method according to claim 18 wherein said at least one excitable tissue control signal parameter is the delay between the detection of a cardiac action potential and the initiation of said excitable tissue control signal and wherein said delay is computed by multiplying said estimated action potential duration value by a first coefficient α

to obtain a first computed value, and by adding a first constant C₁ to said first computed value.

20. The method according to claim 19 wherein said first coefficient α

is in the range of 0.1-0.4.

21. The method according to claim 19 wherein said first coefficient α

is empirically determined for said patient.

22. The method according to claim 18 wherein said at least one excitable tissue control signal parameter is the duration of said excitable tissue control signal, and wherein said duration is computed by multiplying said estimated action potential duration value by a second coefficient β

to obtain a second computed value, and by adding a second constant C₂ to said second computed value.

23. The method according to claim 22 wherein said second coefficient β

is in the range of 0-0.4.

24. The method according to claim 22 wherein said second coefficient β

is empirically determined for said patient.

25. The method according to claim 1 wherein said at least one cardiac action potential related signal of said step of determining comprises a single cardiac action potential related signal and said estimated action potential duration value is determined based on said single cardiac action potential related signal.

26. The method according to claim 1 wherein said at least one cardiac action potential related signal of said step of determining comprises a plurality of cardiac action potential related signals, and wherein said estimated action potential duration value is determined by computing an average estimated action potential duration from the estimated action potential duration values of each cardiac action potential related signal of said plurality of cardiac action potential related signals.

27. The method according to claim 26 wherein said average estimated action potential duration is computed using a method selected from a weighted moving average method and a non-weighted moving average method.

28. The method according to claim 27 wherein said moving average method is implemented using an implementation method selected from a finite impulse response implementation method and an infinite impulse response implementation method.

29. The method according to claim 1 wherein said first site of said heart is identical to said second site of said heart.

30. The method according to claim 1 further comprising the steps of:

comparing said estimated action potential duration value to a value representing the minimal acceptable action potential duration value; and

disabling the delivery of at least one of said excitable tissue control signals to said second site of said heart if said estimated action potential duration value is smaller than said minimal acceptable action potential duration value.

31. The method according to claim 30 wherein said minimal acceptable action potential duration value is a preset value.

32. The method according to claim 31 further including the step of empirically determining said minimal acceptable action potential duration value for said patient.

33. The method according to claim 31 further including the step of modifying said minimal acceptable action potential duration value based on the results of a checkup procedure performed in said patient.

34. The method according to claim 1 further including the step of providing a look up table including a plurality of action potential duration ranges, each action potential duration range of said plurality of action potential duration ranges is associated with at least one excitable tissue control signal parameter value, wherein said step of processing comprises the steps of,

selecting from said look up table the action potential duration range into which said estimated action potential duration value of said step of determining falls, and

selecting the at least one excitable tissue control signal parameter associated with said action potential duration range as said at least one excitable tissue control signal parameter of said step of processing.

35. Apparatus for automatically controlling the delivery of excitable tissue control signals to a heart of a patient, the apparatus comprising:

means for determining an estimated action potential duration value from at least one cardiac action potential related signal sensed at a first cardiac site of said heart;

means for processing said estimated action potential duration value to obtain at least one excitable tissue control signal parameter; and

means for using said at least one parameter to control the delivery of one or more excitable tissue control signals to a second cardiac site of said heart after the time of occurrence of said at least one cardiac action potential related signal of said step of determining.

36. Apparatus for automatically controlling the delivery of excitable tissue control signals to a heart of a patient, the apparatus comprising:

an excitable tissue control unit for delivering said excitable tissue control signals to a first site of said heart;

an action potential duration determining unit operatively connected to said excitable tissue control unit for receiving action potential related signals sensed at a second site of said heart, determining an estimated action potential duration value from at least one of said action potential related signals, computing at least one excitable tissue control signal parameter and controlling the delivery at least one of said excitable tissue control signals based on said at least one excitable tissue control signal parameter; and

a power source for energizing said excitable tissue control unit and said action potential duration determining unit.

37. The apparatus according to claim 36 further including a case for housing said excitable tissue control unit, said action potential duration determining unit and said power source.

38. The apparatus according to claim 36 further including a pacing unit operatively connected to said action potential duration determining unit and connectable to at least one electrode implanted in said heart for controllably delivering pacing pulses to said heart.

39. The apparatus according to claim 36 further including at least one timing unit operatively connected to said action potential duration determining unit for providing timing signals thereto.

40. The apparatus according to claim 36 further including a memory unit operatively connected to said action potential duration determining unit usable for storing and retrieving data by said action potential duration determining unit.

41. The apparatus according to claim 36 wherein said apparatus is provided with a look up table, stored in said memory unit, said look up table includes a plurality of action potential duration ranges, each action potential duration range of said plurality of action potential duration ranges is associated with at least one excitable tissue control signal parameter value, and wherein said action potential duration determining unit is adapted to select from said look up table the action potential duration range into which said estimated action potential duration value falls, and to select the at least one excitable tissue control signal parameter associated with said action potential duration range as said at least one excitable tissue control signal parameter.

42. The apparatus according to claim 36 wherein said apparatus is an implantable apparatus, and wherein said apparatus further includes a telemetry unit operatively connected to said action potential duration determining unit for communicating with another telemetry unit disposed outside said patient.

43. The apparatus according to claim 36 wherein said action potential duration determining unit comprises:

a close bipolar electrogram sensing unit for sensing close bipolar electrogram signals at said second site of said heart;

a digitizing unit operatively connected to said close bipolar electrogram sensing unit for digitizing said close bipolar electrogram signals sensed by said close bipolar electrogram sensing unit to provide digitized close bipolar electrogram signals; and

a microprocessor unit operatively connected to said digitizing unit and said excitable tissue control unit for receiving said digitized close bipolar electrogram signals, determining an estimated action potential duration value from at least one of said digitized close bipolar electrogram signals, computing at least one excitable tissue control signal parameter from said estimated action potential duration value and controlling the delivery of at least one of said excitable tissue control signals based on said at least one excitable tissue control signal parameter.

44. The apparatus according to claim 43 wherein said closed bipolar electrogram sensing unit comprises a differential amplifier connectable to a pair of electrodes for sensing said close bipolar electrogram signals.

45. The apparatus according to claim 43 wherein said microprocessor is adapted to receive said digitized close bipolar electrogram signal and to obtain therefrom a time value usable as the approximate starting time point of the cardiac action potential corresponding with the currently sensed close bipolar electrogram signal.

46. The apparatus according to claim 43 wherein said close bipolar electrogram signal also comprises an artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to said second cardiac site within the duration of sensing said close bipolar electrogram signal, and wherein said microprocessor unit is adapted for processing said close bipolar electrogram signal to reduce or eliminate said artifact component.

47. The apparatus according to claim 43 wherein said at least one excitable tissue control signal parameter computed by said microprocessor unit is selected from the delay between the detection of a cardiac action potential and the initiation of an excitable tissue control signal, the duration of said excitable tissue control signal, the intensity of said excitable tissue control signal, the waveform of said excitable tissue control signal, the polarity of said excitable tissue control signal and any combination thereof.

48. The apparatus according to claim 47 wherein said at least one excitable tissue control signal parameter is the delay between the detection of a cardiac action potential and the initiation of said excitable tissue control signal and wherein said microprocessor unit is adapted for computing said delay by multiplying said estimated action potential duration value by a first coefficient α

to obtain a first computed value, and by adding a first constant C₁ to said first computed value.

49. The apparatus according to claim 48 wherein said first coefficient α

is in the range of 0-0.6.

50. The apparatus according to claim 49 wherein said first coefficient α

is empirically determined for said patient.

51. The apparatus according to claim 47 wherein said at least one excitable tissue control signal parameter is the duration of an excitable tissue control signal, and wherein said duration is computed by multiplying said estimated action potential duration value by a second coefficient β

to obtain a second computed value, and by adding a second constant C₂ to said second computed value.

52. The apparatus according to claim 51 wherein said second coefficient β

is in the range of 0-0.4.

53. The apparatus according to claim 51 wherein said second coefficient β

is empirically determined for said patient.

54. The apparatus according to claim 43 wherein said at least one of said digitized close bipolar electrogram signals is a single digitized close bipolar electrogram signal and said estimated action potential duration value is determined based on said single digitized close bipolar electrogram signal.

55. The apparatus according to claim 43 wherein said at least at least one of said digitized close bipolar electrogram signals comprises a plurality of digitized close bipolar electrogram signals, and wherein said estimated action potential duration value is determined by computing an average estimated action potential duration from the estimated action potential duration values of each digitized close bipolar electrogram signal of said plurality of digitized close bipolar electrogram signals.

56. The apparatus according to claim 55 wherein said microprocessor is adapted to compute said average estimated action potential duration by using a moving average program selected from a weighted moving average program and a non-weighted moving average program.

57. The apparatus according to claim 56 wherein said moving average program is implemented using an implementation method selected from a finite impulse response implementation method and an infinite impulse response implementation method.

58. The apparatus according to claim 43 wherein said microprocessor unit is adapted to disable the delivery of at least one of said excitable tissue control signals to said second site of said heart if said estimated action potential duration value is smaller than a minimal acceptable action potential duration value.

59. The apparatus according to claim 58 wherein said minimal acceptable action potential duration value is a preset value.

60. The apparatus according to claim 43 further including a memory unit operatively connected to said microprocessor unit, wherein said apparatus is provided with a look up table, stored in said memory unit, said look up table includes a plurality of action potential duration ranges, each action potential duration range of said plurality of action potential duration ranges is associated with at least one excitable tissue control signal parameter value, and wherein said action potential duration determining unit is adapted to select from said look up table the action potential duration range into which said estimated action potential duration value falls, and to select the at least one excitable tissue control signal parameter associated with said action potential duration range as said at least one excitable tissue control signal parameter.

61. The apparatus according to claim 43 wherein said close bipolar electrogram signal includes a first signal component representing the differentiated upstroke of the fast depolarization phase of a cardiac action potential and a second signal component representing the differentiated fast repolarization phase of said cardiac action potential, and wherein said microprocessor unit is adapted to determine a first time point at which the amplitude of said first signal component first crosses a first threshold value, determine a second time point at which the amplitude of said second signal component first crosses a second threshold value, and to obtain said estimated action potential duration value by determining the value of the time interval between said second time point and said first time point.

62. The apparatus according to claim 61 wherein said microprocessor unit is adapted to determine the amplitude value of the extremum point of said first signal component and the amplitude value of the extremum point of said second signal component, and wherein said first threshold value is a fraction of the amplitude value of said extremum point of said first signal component and said second threshold value is a fraction of the amplitude value of said extremum point of said second signal component.

63. The apparatus according to claim 62 wherein said first threshold value is 50% of the amplitude value of said extremum point of said first signal component and said second threshold value is 50% of the amplitude value of said extremum point of said second signal component.

64. The apparatus according to claim 36 wherein said at least one of said action potential related signals comprises at least one cardiac close bipolar electrogram signal, and wherein said action potential duration determining unit comprises:

a close bipolar electrogram sensing unit for sensing close bipolar electrogram signals at said second site of said heart;

an action potential duration determining circuit operatively connected to said close bipolar electrogram sensing unit for receiving said close bipolar electrogram signals, and for processing said close bipolar electrogram signals to provide estimated action potential duration values corresponding to said close bipolar electrogram signals; and

a microprocessor unit operatively connected to said action potential duration determining circuit and to said excitable tissue control unit for receiving said estimated action potential duration values, computing at least one excitable tissue control signal parameter from at least one of said estimated action potential duration values and controlling the delivery of at least one of said excitable tissue control signals based on said at least one excitable tissue control signal parameter.

65. The apparatus according to claim 64 wherein said closed bipolar electrogram sensing unit comprises a differential amplifier connectable to a pair of electrodes for sensing said close bipolar electrogram signals.

66. The apparatus according to claim 65 wherein said action potential duration determining circuit comprises:

a first band pass filter operatively connected to the output terminal of said differential amplifier and adapted to preferentially pass a first frequency range corresponding to a first high frequency component of said close bipolar electrogram signals and to produce a first filtered signal;

a second band pass filter operatively connected to the output terminal of said differential amplifier and adapted to preferentially pass a second frequency range corresponding to a second low frequency component of said close bipolar electrogram signals and to produce a second filtered signal;

a first tunable threshold circuit operatively connected to the output terminal of said first band pass filter for generating a first trigger signal when said filtered signal crosses a first threshold value;

a second tunable threshold circuit operatively connected to the output terminal of said second band pass filter for generating a second trigger signal when said second filtered signal crosses a second threshold value; and

an edge activated binary counter operatively connected to said first tunable threshold circuit and to said second tunable threshold circuit for receiving and processing said first trigger signal and said second trigger signal to provide an output signal representing an estimated action potential duration value.

67. The apparatus according to claim 66 wherein said first tunable threshold circuit is also operatively connected to said second tunable threshold circuit such that said first trigger signal is fed as a control signal for activating said second tunable threshold circuit.

68. The apparatus according to claim 66 wherein at least one of said first tunable threshold circuit and said second tunable threshold circuit are operatively connected to said microprocessor for receiving control signals therefrom, said signals selected from disabling signals, enabling signals and a combination of disabling signals and enabling signals.

69. The apparatus according to claim 66 wherein said first tunable threshold circuit generates said first trigger signal when said filtered signal crosses a first threshold value going in a first direction, and wherein said second tunable threshold circuit generates said second trigger signal when said second filtered signal crosses a second threshold value going in a second direction.

70. The apparatus according to claim 66 wherein said first threshold value is a positive threshold value and said second threshold is a negative threshold value.

71. The apparatus according to claim 69 wherein said first threshold value is a positive threshold value and said second threshold is a negative threshold value, and wherein said first direction is a positive going direction and said second direction is a negative going direction.

72. The apparatus according to claim 66 wherein said first threshold value is a negative threshold value and said second threshold is a positive threshold value.

73. The apparatus according to claim 69 wherein said first threshold value is a negative threshold value and said second threshold is a positive threshold value, and wherein said first direction is a negative going direction and said second direction is a positive going direction.

74. The apparatus according to claim 66 wherein said microprocessor is adapted to receive said first trigger signal and to obtain therefrom a time value usable as the approximate starting time point of the cardiac action potential corresponding with the currently sensed close bipolar electrogram signal.

75. The apparatus according to claim 66 wherein said first tunable threshold circuit is operatively connected to said second tunable threshold circuit such that said first trigger signal is fed as a control signal for activating said second tunable threshold circuit.

76. The apparatus according to claim 66 wherein said close bipolar electrogram signal also comprises an artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to said second cardiac site within the duration of sensing said close bipolar electrogram signal, and wherein said microprocessor unit is adapted for processing said close bipolar electrogram signal to reduce or eliminate said artifact component.

77. The apparatus according to claim 76 wherein said microprocessor unit is operatively connected to said second tunable threshold circuit to provide blanking signals thereto for blanking said artifact component.

78. The apparatus according to claim 66 wherein of said first tunable threshold circuit and said second tunable threshold circuit each include an adjustable threshold setting potentiometer for adjusting the threshold level of said first tunable threshold circuit and said second tunable threshold circuit, respectively.

79. The apparatus according to claim 66 wherein said at least one excitable tissue control signal parameter computed by said microprocessor unit is selected from the delay between the detection of a cardiac action potential and the initiation of an excitable tissue control signal, the duration of said excitable tissue control signal, the intensity of said excitable tissue control signal, the waveform of said excitable tissue control signal, the polarity of said excitable tissue control signal and any combination thereof.

80. The apparatus according to claim 79 wherein said at least one excitable tissue control signal parameter is the delay between the detection of a cardiac action potential and the initiation of said excitable tissue control signal and wherein said microprocessor unit is adapted for computing said delay by multiplying said estimated action potential duration value by a first coefficient α

to obtain a first computed value, and by adding a first constant C₁ to said first computed value.

81. The apparatus according to claim 80 wherein said first coefficient α

is in the range of 0-0.6.

82. The apparatus according to claim 81 wherein said first coefficient α

is empirically determined for said patient.

83. The apparatus according to claim 82 wherein said at least one excitable tissue control signal parameter is the duration of an excitable tissue control signal, and wherein said duration is computed by multiplying said estimated action potential duration value by a second coefficient β

to obtain a second computed value, and by adding a second constant C₂ to said second computed value.

84. The apparatus according to claim 83 wherein said second coefficient β

is in the range of 0-0.4.

85. The apparatus according to claim 84 wherein said second coefficient β

is empirically determined for said patient.

86. The apparatus according to claim 64 wherein said at least one close bipolar electrogram signal is a single close bipolar electrogram signal and said estimated action potential duration value is determined based on said single one close bipolar electrogram signal.

87. The apparatus according to claim 64 wherein said at least one close bipolar electrogram signal comprises a plurality of close bipolar electrogram signals, and wherein said estimated action potential duration value is determined by computing an average estimated action potential duration from the estimated action potential duration values of each close bipolar electrogram signal of said plurality of close bipolar electrogram signals.

88. The apparatus according to claim 87 wherein said microprocessor is adapted to compute said average estimated action potential duration by using a moving average program selected from a weighted moving average program and a non-weighted moving average program.

89. The apparatus according to claim 88 wherein said moving average program is implemented using an implementation method selected from a finite impulse response implementation method and an infinite impulse response implementation method.

90. The apparatus according to claim 64 wherein said microprocessor unit is adapted to disable the delivery of at least one of said excitable tissue control signals to said second site of said heart if said estimated action potential duration value is smaller than a minimal acceptable action potential duration value.

91. The apparatus according to claim 90 wherein said minimal acceptable action potential duration value is a preset value.

92. The apparatus according to claim 65 further including a memory unit operatively connected to said microprocessor unit, and wherein said apparatus is provided with a look up table, stored in said memory unit, said look up table includes a plurality of action potential duration ranges, each action potential duration range of said plurality of action potential duration ranges is associated with at least one excitable tissue control signal parameter value, and wherein said action potential duration determining unit is adapted to select from said look up table the action potential duration range into which said estimated action potential duration value falls, and to select the at least one excitable tissue control signal parameter associated with said action potential duration range as said at least one excitable tissue control signal parameter.

93. The apparatus according to claim 36 wherein said action potential duration determining unit comprises:

a monophasic action potential sensing unit for sensing monophasic action potential signals at said second site of said heart;

a digitizing unit operatively connected to said monophasic action potential sensing unit for digitizing said monophasic action potential signals sensed by said monophasic action potential sensing unit to provide digitized monophasic action potential signals; and

a microprocessor unit operatively connected to said digitizing unit and said excitable tissue control unit for receiving said digitized monophasic action potential signals, determining an estimated action potential duration value from at least one of said digitized monophasic action potential signals, computing at least one excitable tissue control signal parameter from said estimated action potential duration value and controlling the delivery of at least one of said excitable tissue control signals based on said at least one excitable tissue control signal parameter.

94. The apparatus according to claim 93 wherein said microprocessor is adapted to receive said digitized monophasic action potential signal and to obtain therefrom a time value usable as the approximate starting time point of the cardiac action potential corresponding with the currently sensed monophasic action potential signal.

95. The apparatus according to claim 93 wherein said digitized monophasic action potential signal also comprises an artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to said second cardiac site within the duration of sensing said monophasic action potential signal, and wherein said microprocessor unit is adapted for processing said digitized monophasic action potential signal to reduce or eliminate said artifact component.

96. The apparatus according to claim 93 wherein said at least one excitable tissue control signal parameter computed by said microprocessor unit is selected from the delay between the detection of a cardiac action potential and the initiation of an excitable tissue control signal, the duration of said excitable tissue control signal, the intensity of said excitable tissue control signal, the waveform of said excitable tissue control signal, the polarity of said excitable tissue control signal and any combination thereof.

97. The apparatus according to claim 96 wherein said at least one excitable tissue control signal parameter is the delay between the detection of a cardiac action potential and the initiation of said excitable tissue control signal and wherein said microprocessor unit is adapted for computing said delay by multiplying said estimated action potential duration value by a first coefficient α

to obtain a first computed value, and by adding a first constant C₁ to said first computed value.

98. The apparatus according to claim 97 wherein said first coefficient α

is in the range of 0-0.6.

99. The apparatus according to claim 97 wherein said first coefficient α

is empirically determined for said patient.

100. The apparatus according to claim 96 wherein said at least one excitable tissue control signal parameter is the duration of an excitable tissue control signal, and wherein said duration is computed by multiplying said estimated action potential duration value by a second coefficient β

to obtain a second computed value, and by adding a second constant C₂ to said second computed value.

101. The apparatus according to claim 100 wherein said second coefficient β

is in the range of 0-0.4.

102. The apparatus according to claim 100 wherein said second coefficient β

is empirically determined for said patient.

103. The apparatus according to claim 93 wherein said at least one of said digitized monophasic action potential signals is a single digitized monophasic action potential signal and said estimated action potential duration value is determined based on said single digitized monophasic action potential signal.

104. The apparatus according to claim 93 wherein said at least one of said digitized monophasic action potential signals comprises a plurality of digitized monophasic action potential signals, and wherein said estimated action potential duration value is determined by computing an average estimated action potential duration from the estimated action potential duration values of each digitized monophasic action potential signal of said plurality of digitized monophasic action potential signals.

105. The apparatus according to claim 104 wherein said microprocessor is adapted to compute said average estimated action potential duration by using a moving average program selected from a weighted moving average program and a non-weighted moving average program.

106. The apparatus according to claim 105 wherein said moving average program is implemented using an implementation method selected from a finite impulse response implementation method and an infinite impulse response implementation method.

107. The apparatus according to claim 93 wherein said microprocessor unit is adapted to disable the delivery of at least one of said excitable tissue control signals to said second site of said heart if said estimated action potential duration value is smaller than a minimal acceptable action potential duration value.

108. The apparatus according to claim 107 wherein said minimal acceptable action potential duration value is a preset value.

109. The apparatus according to claim 93 further including a memory unit operatively connected to said microprocessor unit, wherein said apparatus is provided with a look up table, stored in said memory unit, said look up table includes a plurality of action potential duration ranges, each action potential duration range of said plurality of action potential duration ranges is associated with at least one excitable tissue control signal parameter value, and wherein said action potential duration determining unit is adapted to select from said look up table the action potential duration range into which said estimated action potential duration value falls, and to select the at least one excitable tissue control signal parameter associated with said action potential duration range as said at least one excitable tissue control signal parameter.

110. The apparatus according to claim 93 wherein said monophasic action potential signal comprises a sharp leading edge related to the fast depolarization phase of a cardiac action potential and has a maximal amplitude value, and wherein said microprocessor unit is adapted to determine a first time point at which the amplitude of said sharp leading edge first crosses a first threshold value, determine said maximal amplitude value, determine a second time point at which the amplitude value of said monophasic action potential signal is equal to a fraction of said maximal amplitude value, and obtain said estimated action potential duration value by determining the value of the time interval between said second time point and said first time point.

111. The apparatus according to claim 110 wherein said second time point is the time point at which said amplitude value of said monophasic action potential signal is equal to 10% of said maximal amplitude value and said estimated action potential duration value is the MAP₉₀ value.

112. The apparatus according to claim 36 wherein said at least one of said action potential related signals comprises at least one cardiac monophasic action potential, and wherein said action potential duration determining unit comprises:

a monophasic action potential sensing unit for sensing monophasic action potential signals at said second site of said heart;

an action potential duration determining circuit operatively connected to said monophasic action potential sensing unit for receiving said monophasic action potential signals and processing said monophasic action potential signals to provide estimated action potential duration values corresponding to said monophasic action potential signals; and

a microprocessor unit operatively connected to said action potential duration determining circuit and to said excitable tissue control unit for receiving said estimated action potential duration values, computing at least one excitable tissue control signal parameter from at least one of said estimated action potential duration values and controlling the delivery of at least one of said excitable tissue control signals based on said at least one excitable tissue control signal parameter.

113. The apparatus according to claim 112 wherein each of said monophasic action potential signals comprises a leading edge signal component related to the fast repolarization phase of a cardiac action potential and a maximal amplitude value, and wherein said action potential duration determining circuit comprises:

a high pass filter operatively connected to the output terminal of said monophasic action potential sensing unit and adapted to preferentially pass a first frequency range to produce a high pass filtered signal;

a low pass filter operatively connected to the output terminal of said monophasic action potential sensing unit and adapted to preferentially pass a second frequency range to produce a low pass filtered signal;

a first comparator operatively connected to the output terminal of said high pass filter for generating a first trigger signal when said high pass filtered signal crosses a first threshold value;

a peak detector circuit having an input terminal operatively connected to the output terminal of said low pass filter and an output terminal connected to a first potentiometer, for receiving said low pass filtered signal from said low pass filter and for detecting and holding said maximal amplitude value at said output terminal of said peak detector;

a second comparator operatively connected to the output terminal of said low pass filter and to the variable terminal of said potentiometer for generating a second trigger signal when the amplitude of said low pass filtered signal is equal to a fraction of said maximal amplitude value;

an edge activated binary counter operatively connected to said first comparator and to said second comparator for receiving said first trigger signal and said second trigger signal and for providing to said microprocessor unit an output signal representing an estimated action potential duration value.

114. The apparatus according to claim 113 wherein said microprocessor is adapted to receive said first trigger signal and to obtain therefrom a time value usable as the approximate starting time point of the cardiac action potential corresponding with the currently sensed monophasic action potential signal.

115. The apparatus according to claim 113 wherein said first comparator is operatively connected to said second comparator such that said first trigger signal is fed as a control signal for activating said second comparator.

116. The apparatus according to claim 113 wherein said monophasic action potential signal also comprises a artifact component representing an electrical artifact induced by the delivery of an excitable tissue control signal to said second cardiac site within the duration of sensing said monophasic action potential signal, and wherein said microprocessor unit is adapted for processing said monophasic action potential signal to reduce or eliminate said artifact component.

117. The apparatus according to claim 116 wherein said microprocessor unit is operatively connected to at least one of said second comparator and said peak detector to provide blanking signals thereto for reducing or eliminating said artifact component.

118. The apparatus according to claim 113 wherein said peak detector is operatively connected to said microprocessor unit to receive control signals therefrom for resetting said peak detector after said second trigger signal is generated by said second comparator.

119. The apparatus according to claim 113 wherein said fraction of said maximal amplitude value is set by adjusting said potentiometer.

120. The apparatus according to claim 113 wherein said at least one excitable tissue control signal parameter computed by said microprocessor unit is selected from the delay between the detection of a cardiac action potential and the initiation of an excitable tissue control signal, the duration of said excitable tissue control signal, the intensity of said excitable tissue control signal, the waveform of said excitable tissue control signal, the polarity of said excitable tissue control signal and any combination thereof.

121. The apparatus according to claim 120 wherein said at least one excitable tissue control signal parameter is the delay between the detection of a cardiac action potential and the initiation of said excitable tissue control signal and wherein said microprocessor unit is adapted for computing said delay by multiplying said estimated action potential duration value by a first coefficient α

to obtain a first computed value, and by adding a first constant C₁ to said first computed value.

122. The apparatus according to claim 121 wherein said first coefficient α

is in the range of 0-0.6.

123. The apparatus according to claim 122 wherein said first coefficient α

is empirically determined for said patient.

124. The apparatus according to claim 120 wherein said at least one excitable tissue control signal parameter is the duration of an excitable tissue control signal, and wherein said duration is computed by multiplying said estimated action potential duration value by a second coefficient β

to obtain a second computed value, and by adding a second constant C₂ to said second computed value.

125. The apparatus according to claim 124 wherein said second coefficient β

is in the range of 0-0.4.

126. The apparatus according to claim 124 wherein said second coefficient β

is empirically determined for said patient.

127. The apparatus according to claim 124 wherein said at least one monophasic action potential is a single monophasic action potential and said estimated action potential duration value is determined based on said single monophasic action potential.

128. The apparatus according to claim 112 wherein said at least one monophasic action potential comprises a plurality of monophasic action potentials, and wherein said estimated action potential duration value is determined by computing an average estimated action potential duration from the estimated action potential duration values of each monophasic action potential of said plurality of monophasic action potentials.

129. The apparatus according to claim 128 wherein said microprocessor is adapted to compute said average estimated action potential duration by using a moving average program selected from a weighted moving average program and a non-weighted moving average program.

130. The apparatus according to claim 129 wherein said moving average program is implemented using an implementation method selected from a finite impulse response implementation method and an infinite impulse response implementation method.

131. The apparatus according to claim 112 wherein said microprocessor unit is adapted to disable the delivery of at least one of said excitable tissue control signals to said second site of said heart if said estimated action potential duration value is smaller than a minimal acceptable action potential duration value.

132. The apparatus according to claim 131 wherein said minimal acceptable action potential duration value is a preset value.

133. The apparatus according to claim 113 further including a memory unit operatively connected to said microprocessor unit, and wherein said apparatus is provided with a look up table, stored in said memory unit, said look up table includes a plurality of action potential duration ranges, each action potential duration range of said plurality of action potential duration ranges is associated with at least one excitable tissue control signal parameter value, and wherein said action potential duration determining unit is adapted to select from said look up table the action potential duration range into which said estimated action potential duration value falls, and to select the at least one excitable tissue control signal parameter associated with said action potential duration range as said at least one excitable tissue control signal parameter.