Pacing methods and devices using feedback controlled timing

• US 20040024421A1
• Filed: 07/31/2002
• Published: 02/05/2004
• Est. Priority Date: 07/31/2002
• Status: Active Grant

• Current Assignee: UAB Research Foundation (University of Alabama System)
• Original Assignee: UAB Research Foundation (University of Alabama System)
• Inventors: Ideker, Raymond E., Walcott, Gregory P.
• Granted Patent: US 7,139,608 B2
• Time in Patent Office: Days
• US Class Current: 607/9
• CPC Class Codes: A61N 1/36521 the parameter being derived from measurement of an electrical impedance
• CPC Class Codes: A61N 1/36578 controlled by mechanical motion of the heart wall, e.g. measured by an accelerometer or microphone
• CPC Class Codes: A61N 1/368 comprising more than one electrode co-operating with different heart regions A61N1/3622, A61N1/3627 take precedence
• CPC Class Codes: A61N 1/3682 with a variable atrioventricular delay
• CPC Class Codes: A61N 1/3684 for stimulating the heart at multiple sites of the ventricle or the atrium
• CPC Class Codes: A61N 1/36843 Bi-ventricular stimulation

Abstract

Methods, systems and computer program products for cardiac pacing are provided. For pacing using biventricular synchronization in a patient, a first stimulation signal is applied to a first region of a heart of the patient at a first time and a second stimulation signal applied to a second region of the heart of the patient at a second time to provide biventricular synchronization stimulation of the heart. Cardiac function of the patient associated with application of the first and the second stimulation signals is sensed and a timing relationship of the first stimulation signal to the second stimulation signal is adjusted based on the sensed cardiac function. Additionally, a cardiac timing interval, such as the A-V timing interval, may be adjusted by applying stimulation to a heart of the patient utilizing a cardiac timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the cardiac timing interval and adjusting the cardiac timing interval directly from the detected change in cardiac function.

Claims

1. A method of pacing in a patient by biventricular synchronization, comprising:

applying a first stimulation signal to a first region of a heart of the patient at a first time;

applying a second stimulation signal to a second region of the heart of the patient at a second time so as to provide biventricular synchronization treatment to the heart;

sensing cardiac function associated with application of the first and the second stimulation signals; and

adjusting a timing relationship of application of the first stimulation signal with respect to application of the second stimulation signal based on the sensed cardiac function.

2. The method of claim 1, wherein the step of sensing cardiac function comprises sensing changes in impedance and wherein the step of adjusting a timing relationship comprises adjusting a timing relationship based on the sensed changes in impedance.

3. The method of claim 2, wherein the step of sensing changes in impedance comprises measuring impedance utilizing a conductance catheter positioned proximate a left ventricle of the heart of the patient.

4. The method of claim 1, wherein the step of sensing cardiac function comprises measuring changes in distance and/or the rate of change in distance between at least two locations on the heart of the patient and wherein the step of adjusting a timing relationship comprises the step of adjusting a timing relationship based on the changes in distance and/or the rate of change in distance.

5. The method of claim 4, wherein the step of measuring changes in distance and/or the rate of change in distance comprises measuring changes in distance and/or the rate of change in distance between at least an electrode positioned on a left ventricle and an electrode positioned within a right ventricle of the heart of the patient.

6. The method of claim 4, wherein the step of measuring changes in distance and/or the rate of change in distance comprises measuring changes in distance and/or the rate of change in distance utilizing ultrasonic crystals.

7. The method of claim 6, wherein the ultrasonic crystals are placed on electrodes that receive the first and the second stimulation signals.

8. The method of claim 1, wherein the step of sensing cardiac function comprises measuring motion of a location associated with the heart of the patient and wherein the step of adjusting a timing relationship comprises adjusting a timing relationship based on the measured motion.

9. The method of claim 8, wherein the location associated with the heart of the patient comprises a left ventricle of the heart of the patient.

10. The method of claim 8, wherein the step of measuring motion comprises detecting motion utilizing an accelerometer.

11. The method of claim 10, further comprising:

determining a derivative of the detected motion; and

estimating cardiac function based on the determined derivative.

12. The method of claim 10, further comprising:

determining an integral of the detected motion; and

estimating cardiac function based on the determined integral.

13. The method of claim 10, further comprising estimating cardiac function based on the detected motion and wherein the step of adjusting a timing relationship comprises adjusting a timing relationship based on the estimated cardiac function.

14. The method of claim 1, further comprising repeating applying a first stimulation signal to a heart of the patient at a first time, applying a second stimulation signal to the heart of the patient at a second time, sensing cardiac function associated with application of the first and the second stimulation and a adjusting a timing relationship of application of the first stimulation signal with respect to application of the second stimulation signal based on the sensed cardiac function until adjusting the timing relationship does not improve cardiac function.

15. The method of claim 14, wherein the step of repeating further comprises:

adjusting timing of application of one of the first stimulation signal and the second stimulation signal until adjustment of the timing of application of the-one of the first stimulation signal and the second stimulation signal does not improve cardiac function; and

then

adjusting timing of application of the other of the first stimulation signal and the second stimulation signal until adjustment of the timing of application of the other of the first stimulation signal and the second stimulation signal does not improve cardiac function.

16. The method of claim 14, further comprising:

determining if a predefined time interval has expired; and

carrying out the steps of applying a first stimulation, applying a second stimulation, sensing, adjusting and repeating if the predefined time interval has expired.

17. The method of claim 14, further comprising:

determining if a change in cardiac function has occurred; and

carrying out the steps of applying a first stimulation, applying a second stimulation, sensing, adjusting and repeating if a change in cardiac function has occurred.

18. The method of claim 14, further comprising:

receiving an external signal initiating recalibration of biventricular synchronization timing; and

carrying out the steps of applying a first stimulation, applying a second stimulation, sensing, adjusting and repeating responsive to receipt of the external signal.

19. The method of claim 1, wherein the steps of sensing and adjusting are preformed each time the first and second simulation signals are applied to the heart of the patient.

20. The method of claim 1, wherein the steps of applying a first stimulation signal to a heart of the patient at a first time, applying a second stimulation signal to the heart of the patient at a second time, sensing cardiac function of the patient associated with application of the first and the second stimulation signals and adjusting a timing relationship of application of the first stimulation signal with respect to application of the second stimulation signal based on the sensed cardiac function are carried out by an implantable pacing device.

21. The method of claim 1, wherein the step of sensing cardiac function further comprises at least one of sensing heart rate of the patient and/or sensing timing and/or morphology of at least one intrinsic ventricular beat of the heart of the patient.

22. The method of claim 14, wherein the step of repeating is successively repeated utilizing finer timing adjustment intervals.

23. The method of claim 1, wherein the step of adjusting a timing relationship comprises delaying the second stimulation signal with respect to the first stimulation signal.

24. The method of claim 1, wherein the step of adjusting a timing relationship comprises advancing the second stimulation signal with respect to the first stimulation signal.

25. The method of claim 1, wherein the timing of the first and the second stimulation signals are established with reference to a common reference signal.

26. The method of claim 25, wherein the common reference signal comprises a spontaneous atrial signal.

27. The method of claim 1, further comprising the steps of:

applying stimulation to a heart of the patient utilizing an A-V timing interval;

detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval; and

adjusting the A-V timing interval based on the detected change in cardiac function.

28. The method of claim 27, further comprising the step of repeating applying stimulation to a heart of the patient utilizing an A-V timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval and adjusting the A-V timing interval based on the detected change in cardiac function until the sensed cardiac function does not indicate an improvement in cardiac function.

29. The method of claim 28, wherein the step of adjusting the A-V timing interval comprises adjusting the A-V timing interval by a predefined interval adjustment value that is independent of the sensed cardiac function.

30. A cardiac pacing system utilizing biventricular synchronization, comprising:

an electrode stimulation timing circuit configured to control timing between application of stimulation to a first electrode and application of stimulation to a second electrode to provide biventricular synchronization;

a cardiac function sensing circuit; and

a feedback control circuit operatively associated with the electrode stimulation timing circuit and the cardiac function sensing circuit and configured to adjust the timing of application of stimulation to the first electrode and application of stimulation to the second electrode based on sensed cardiac function.

31. The system of claim 30, wherein the cardiac function sensing circuit is configured to sense changes in impedance of at least one region of the heart.

32. The system of claim 31, further comprising a conductance catheter configured to be positioned on a left ventricle of the heart of the patient and wherein the cardiac function sensing circuit is operably associated with the conductance catheter.

33. The system of claim 30, wherein the cardiac function sensing circuit is configured to measure changes in distance and/or the rate of change in distance between at least two locations on the heart of the patient.

34. The system of claim 33, wherein cardiac function sensing circuit is further configured to measure changes in distance and/or the rate of change in distance between at least an electrode positioned on a left ventricle and an electrode positioned within a right ventricle of the heart of the patient.

35. The system of claim 33, further comprising ultrasonic crystals positioned on the first electrode and the second electrode and wherein the cardiac function sensing circuit is further configured to measure changes in distance and/or the rate of change in distance utilizing the ultrasonic crystals.

36. The system of claim 30, wherein the cardiac function sensing circuit is configured to measure motion of a location associated with the heart of the patient.

37. The system of claim 36, wherein the location associated with the heart of the patient comprises proximate a left ventricle of the heart of the patient.

38. The system of claim 36, wherein the cardiac function sensing circuit is further configured to detect motion utilizing an accelerometer.

39. The system of claim 38, wherein the cardiac function sensing circuit is further configured to determine a derivative of the detected motion and estimate cardiac function based on the determined derivative.

40. The system of claim 38, wherein the cardiac function sensing circuit is further configured to determine an integral of the detected motion and estimate cardiac function based on the determined integral.

41. The system of claim 38, wherein the cardiac function sensing circuit is further configured to estimate cardiac function based on the detected motion.

42. The system of claim 30, wherein the timing circuit, sensing circuit and feedback circuit are further configured to repeatedly apply a first stimulation to a heart of the patient at a first time, apply a second stimulation to the heart of the patient at a second time, sense cardiac function of the patient resulting from application of the first and the second stimulation and adjust timing of the first stimulation and/or the second stimulation based on the sensed cardiac function until adjusting timing does not improve cardiac function.

43. The system of claim 30, wherein the timing circuit, sensing circuit and feedback circuit are further configured to adjust timing of one of the first stimulation and the second stimulation until adjustment of timing of the one of the first stimulation and the second stimulation does not improve cardiac function and then adjust timing of the other of the first stimulation and the second stimulation until adjustment of timing of the other of the first stimulation and the second stimulation does not improve cardiac function.

44. The system of claim 42, wherein the timing circuit, sensing circuit and feedback circuit are further configured to repeat adjust timing between stimulation of the first electrode and stimulation of the second electrode after a predefined time interval has elapsed.

45. The system of claim 42, wherein the sensing circuit is further configured to determine if a change in cardiac function has occurred;

and

wherein the timing circuit, sensing circuit and feedback circuit are further configured to adjust the timing between stimulation of the first electrode and stimulation of the second electrode if a change in cardiac function has occurred.

46. The system of claim 42, wherein the feedback circuit is further configured to receive an external signal initiating recalibration of biventricular synchronization timing;

and

wherein the timing circuit, sensing circuit and feedback circuit are further configured to adjust the timing between stimulation of the first electrode and stimulation of the second electrode responsive to receipt of the external signal.

47. The system of claim 30, wherein the sensing circuit is configured to sense cardiac function each time the first and second simulations are applied to the heart of the patient and wherein the feedback circuit is configured to adjust timing each time the first and second simulations are applied to the heart of the patient.

48. The system of claim 30, wherein the timing circuit, the sensing circuit and/or the feedback circuit comprise an implantable pacing device.

49. The system of claim 30, wherein the cardiac function sensing circuit is further configured to sense heart rate of the patient and/or timing and/or morphology of at least one intrinsic ventricular beat of the heart of the patient.

50. The system of claim 40, wherein the timing circuit is configured to adjust the timing between the stimulation of the first electrode and the stimulation of the second electrode utilizing variable timing adjustment intervals.

51. The system of claim 30, wherein the timing control circuit adjusts timing by delaying the second stimulation with respect to the first stimulation.

52. The system of claim 30, wherein the timing control circuit adjusts timing by advancing the second stimulation with respect to the first stimulation.

53. The system of claim 30, wherein the timing control circuit adjusts timing of the first and the second stimulation signals with reference to a common reference signal.

54. The system of claim 53, wherein the common reference signal comprises a spontaneous atrial signal.

55. The system of claim 30, wherein the feedback circuit adjusts timing of stimulation of the first electrode with respect to stimulation of the second electrode proportional to the sensed cardiac function.

56. The system of claim 30, wherein the electrode stimulation timing circuit is further configured to provide cardiac stimulation at an A-V timing interval;

and

wherein the feedback control circuit is further configured to adjust the A-V timing interval based on a change in the sensed cardiac function.

57. The method of claim 30, wherein the feedback control circuit is further configured to adjust the A-V timing interval by a predefined interval adjustment value that is independent of the sensed cardiac function.

58. A system for cardiac pacing in a patient by biventricular synchronization, comprising:

means for applying a first stimulation signal to a first region of a heart of the patient at a first time;

means for applying a second stimulation signal to a second region of the heart of the patient at a second time so as to provide biventricular synchronization treatment to the heart;

means for sensing cardiac function associated with application of the first and the second stimulation signals; and

means for adjusting a timing relationship of application of the first stimulation signal with respect to application of the second stimulation signal based on the sensed cardiac function.

59. The system of claim 58, wherein the means for sensing cardiac function comprises means for sensing changes in impedance.

60. The system of claim 59, wherein the means for sensing changes in impedance comprises measuring impedance utilizing a conductance catheter positioned on a left ventricle of the heart of the patient.

61. The system of claim 58, wherein the means for sensing cardiac function comprises means for measuring changes in distance and/or the rate of change in distance between at least two locations on the heart of the patient.

62. The system of claim 61, wherein the means for measuring changes in distance and/or the rate of change in distance comprises means for measuring changes in distance and/or the rate of change in distance between at least an electrode positioned proximate a left ventricle and an electrode positioned within a right ventricle of the heart of the patient.

63. The system of claim 61, wherein the means for measuring changes in distance and/or the rate of change in distance comprises means for measuring changes in distance and/or the rate of change in distance utilizing ultrasonic crystals.

64. The system of claim 63, wherein the ultrasonic crystals are placed on electrodes the first and the second electrodes.

65. The system of claim 58, wherein the means for sensing cardiac function comprises means for measuring motion of a location associated with the heart of the patient.

66. The system of claim 65, wherein the location associated with the heart of the patient comprises a left ventricle of the heart of the patient.

67. The system of claim 65, wherein the means for measuring motion comprises an accelerometer.

68. The system of claim 65, further comprising:

means for determining a derivative of the detected motion; and

means for estimating cardiac function based on the determined derivative.

69. The system of claim 65, further comprising:

means for determining an integral of the detected motion; and

means for estimating cardiac function based on the determined integral.

70. The system of claim 67, wherein the means for sensing further comprise means for estimating cardiac function based on the detected motion.

71. The system of claim 58, further comprising means for repeatedly applying a first stimulation signal to a heart of the patient at a first time, applying a second stimulation signal to the heart of the patient at a second time, sensing cardiac function of the patient associated with application of the first and the second stimulation and adjusting a timing relationship until adjusting timing does not improve cardiac function.

72. The system of claim 71, wherein the means for repeatedly applying further comprises:

means for adjusting timing of one of the first stimulation signal and the second stimulation signal until adjustment of timing of the one of the first stimulation signal and the second stimulation signal does not improve cardiac function and then adjusting timing of the other of the first stimulation signal and the second stimulation signal until adjustment of timing of the other of the first stimulation signal and the second stimulation signal does not improve cardiac function.

73. The system of claim 71, further comprising:

means for determining if a predefined time interval has expired; and

wherein the means for repeatedly applying is responsive to the means for determining if a predetermined time interval has expired.

74. The system of claim 71, further comprising:

means for determining if a change in cardiac function has occurred; and

wherein the means for repeatedly applying is responsive to the means for determining if a change in cardiac function has occurred.

75. The system of claim 71, further comprising:

means for receiving an external signal initiating recalibration of biventricular synchronization timing; and

wherein the means for repeatedly applying is responsive to the means for receiving an external signal.

76. The system of claim 58, wherein the means for sensing and means for adjusting are responsive to each application of the first and second simulation signals to the heart.

77. The system of claim 58, wherein the means for applying a first stimulation signal to a heart of the patient at a first time, the means for applying a second stimulation signal to the heart of the patient at a second time, the means for sensing cardiac function of the patient associated with application of the first and the second stimulation and/or the means for adjusting a timing relationship comprise an implantable pacing device.

78. The system of claim 58, wherein the means for sensing cardiac function further comprises means for sensing a heart rate of the patient and/or sensing timing and/or morphology of at least one intrinsic ventricular beat of the heart of the patient.

79. The system of claim 71, wherein the means for adjusting timing utilizes successively finer timing adjustment intervals.

80. The system of claim 58, wherein the means for adjusting timing comprises means for delaying the second stimulation signal with respect to the first stimulation signal.

81. The system of claim 58, wherein the means for adjusting timing comprises means for advancing the second stimulation signal with respect to the first stimulation signal.

82. The system of claim 58, wherein the means for adjusting timing comprises means for adjusting timing of the first and the second stimulation signals with reference to a common reference signal.

83. The system of claim 82, wherein the common reference signal comprises a spontaneous atrial signal.

84. The system of claim 58, further comprising:

means for applying stimulation to a heart of the patient utilizing an A-V timing interval;

means for detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval; and

means for adjusting the A-V timing interval based on the detected change in cardiac function.

85. The system of claim 84, wherein the means for adjusting the A-V timing interval comprises means for adjusting the A-V timing interval by a predefined interval adjustment value that is independent of the sensed cardiac function.

86. A computer program product for controlling pacing in a patient by biventricular synchronization, comprising:

a computer readable medium having computer readable program code embodied therein, the computer readable program code comprising;

computer readable program code configured to apply a first stimulation signal to a first region of a heart of the patient at a first time;

computer readable program code configured to apply a second stimulation signal to a second region of the heart of the patient at a second time so as to provide biventricular synchronization treatment to the heart;

computer readable program code configured to sense cardiac function associated with application of the first and the second stimulation signals; and

computer readable program code configured to adjust a timing relationship of application of the first stimulation signal with respect to application of the second stimulation signal based on the sensed cardiac function.

87. The computer program product of claim 86, further comprising:

computer readable program code configured to apply stimulation to a heart of the patient utilizing an A-V timing interval;

computer readable program code configured to detect a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval; and

computer readable program code configured to adjust the A-V timing interval based on the detected change in cardiac function.

88. A method of cardiac pacing in a patient, comprising:

applying stimulation to a heart of the patient utilizing a cardiac timing interval;

detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the cardiac timing interval; and

adjusting the cardiac timing interval directly from the detected change in cardiac function.

89. The method of claim 88, wherein the cardiac timing interval comprises a pacing interval.

90. The method of claim 88, wherein the step of applying stimulation comprises applying stimulation to the heart utilizing a single electrode.

91. The method of claim 88, wherein the cardiac timing interval comprises a timing interval from a reference signal to a left ventricular stimulation and/or a timing interval from the reference signal to a right ventricular stimulation.

92. The method of claim 91, wherein the cardiac timing interval is adjusted so as to adjust a timing relationship between the left ventricular stimulation and the right ventricular stimulation.

93. The method of claim 91, wherein the cardiac timing interval is adjusted so as to adjust a timing between both the left ventricular stimulation and the right ventricular stimulation and the reference signal.

94. The method of claim 91, wherein the reference signal comprises a spontaneous atrial signal.

95. The method of claim 91, wherein the reference signal comprises a pacing stimulation.

96. The method of claim 88, wherein the cardiac timing interval comprises an A-V timing interval.

97. The method of claim 96, wherein the step of detecting a change in cardiac function comprises detecting a change in cardiac function by sensing changes in impedance and wherein the step of adjusting the A-V timing interval comprises adjusting the A-V timing interval directly from the sensed changes in impedance.

98. The method of claim 97, wherein the step of detecting a change in cardiac function by sensing changes in impedance comprises detecting a change in cardiac function by measuring impedance utilizing a conductance catheter positioned proximate a left ventricle of the heart of the patient.

99. The method of claim 96, wherein the step of detecting a change in cardiac function by sensing cardiac function comprises detecting a change in cardiac function by measuring changes in distance and/or the rate of change in distance between at least two locations on the heart of the patient and wherein the step of adjusting the A-V timing interval comprises the step of adjusting the A-V timing interval directly from the changes in distance and/or the rate of change in distance.

100. The method of claim 99, wherein the step of detecting a change in cardiac function by measuring changes in distance and/or the rate of change in distance comprises detecting a change in cardiac function by measuring changes in distance and/or the rate of change in distance between at least an electrode positioned on a left ventricle and an electrode positioned within a right ventricle of the heart of the patient.

101. The method of claim 99, wherein the step of detecting a change in cardiac function by measuring changes in distance and/or the rate of change in distance comprises detecting a change in cardiac function by measuring changes in distance and/or the rate of change in distance utilizing ultrasonic crystals.

102. The method of claim 101, wherein the ultrasonic crystals are placed on electrodes that receive the first and the second stimulation signals.

103. The method of claim 96, wherein the step of detecting a change in cardiac function by sensing cardiac function comprises detecting a change in cardiac function by measuring motion of a location associated with the heart of the patient and wherein the step of adjusting the A-V timing interval comprises adjusting the A-V timing interval directly from the measured motion.

104. The method of claim 103, wherein the location associated with the heart of the patient comprises a left ventricle of the heart of the patient.

105. The method of claim 103, wherein the step of detecting a change in cardiac function by measuring motion comprises detecting motion utilizing an accelerometer.

106. The method of claim 105, further comprising:

determining a derivative of the detected motion; and

estimating cardiac function based on the determined derivative.

107. The method of claim 105, further comprising:

determining an integral of the detected motion; and

estimating cardiac function based on the determined integral.

108. The method of claim 105, further comprising estimating cardiac function based on the detected motion and wherein the step of adjusting a timing relationship comprises adjusting the A-V timing directly from the estimated cardiac function.

109. The method of claim 96, further comprising repeating applying stimulation to a heart of the patient utilizing an A-V timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval and adjusting the A-V timing interval directly from the detected change in cardiac function until adjusting the A-V timing interval does not improve cardiac function.

110. The method of claim 109, further comprising:

determining if a predefined time interval has expired; and

carrying out the steps of applying stimulation to a heart of the patient utilizing an A-V timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval, adjusting the A-V timing interval directly from the detected change in cardiac function and repeating if the predefined time interval has expired.

111. The method of claim 109, further comprising:

determining if a change in cardiac function has occurred; and

carrying out the steps of applying stimulation to a heart of the patient utilizing an A-V timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval, adjusting the A-V timing interval directly from the detected change in cardiac function and repeating if a change in cardiac function has occurred.

112. The method of claim 109, further comprising:

receiving an external signal initiating recalibration of A-V interval timing; and

carrying out the steps of applying stimulation to a heart of the patient utilizing an A-V timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval, adjusting the A-V timing interval directly from the detected change in cardiac function and repeating responsive to receipt of the external signal.

113. The method of claim 96, wherein the steps of detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval, adjusting the A-V timing interval directly from the detected change in cardiac function are preformed each time the stimulation is applied.

114. The method of claim 96, wherein the steps of applying stimulation to a heart of the patient utilizing an A-V timing interval, detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the A-V timing interval and adjusting the A-V timing interval directly from the detected change in cardiac function are carried out by an implantable pacing device.

115. The method of claim 96, wherein the step of detecting a change in cardiac function by sensing cardiac function further comprises at least one of sensing heart rate of the patient and/or sensing timing and/or morphology of at least one intrinsic ventricular beat of the heart of the patient.

116. The method of claim 100, wherein the step of adjusting the A-V timing interval comprises adjusting the A-V timing interval utilizing a variable adjustment interval.

117. The method of claim 110, wherein the step of repeating is successively repeated utilizing finer timing adjustment intervals.

118. The method of claim 96, wherein the step of adjusting the A-V timing interval comprises increasing the A-V timing interval.

119. The method of claim 96, wherein the step of adjusting the A-V timing interval comprises decreasing the A-V timing interval.

120. The method of claim 96, wherein the step of adjusting the A-V timing interval comprises adjusting the A-V timing interval utilizing a fixed adjustment interval.

121. A system for cardiac pacing in a patient, comprising:

an electrode stimulation timing circuit configured to control a cardiac timing interval of application of stimulation to a heart of the patient;

a cardiac function sensing circuit configured to detect a change in cardiac function by sensing cardiac function associated with application of the stimulation; and

a feedback control circuit operatively associated with the electrode stimulation timing circuit and the cardiac function sensing circuit and configured to adjust the cardiac timing interval directly from the detected change in cardiac function.

122. The system of claim 121, wherein the cardiac timing interval comprises a pacing interval.

123. The system of claim 121, wherein the cardiac timing interval comprises an A-V timing interval.

124. The system of claim 121, wherein the cardiac timing interval comprises a timing interval from a reference signal to a left ventricular stimulation and/or a timing interval from the reference signal to a right ventricular stimulation.

125. A system for cardiac pacing in a patient, comprising:

means for applying stimulation to a heart of the patient utilizing a cardiac timing interval;

means for detecting a change in cardiac function by sensing cardiac function associated with application of the stimulation using the cardiac timing interval; and

means for adjusting the cardiac timing interval directly from the detected change in cardiac function.

126. The system of claim 125, wherein the cardiac timing interval comprises a pacing interval.

127. The system of claim 125, wherein the cardiac timing interval comprises an A-V timing interval.

128. The system of claim 125, wherein the cardiac timing interval comprises a timing interval from a reference signal to a left ventricular stimulation and/or a timing interval from the reference signal to a right ventricular stimulation.

129. A computer program product for controlling cardiac pacing in a patient, comprising:

a computer readable medium having computer readable program code embodied therein, the computer readable program code comprising;

computer readable program code configured to apply stimulation to a heart of the patient utilizing a cardiac timing interval;

computer readable program code configured to detect a change in cardiac function by sensing cardiac function associated with application of the stimulation using the cardiac timing interval; and

computer readable program code configured to adjust the A-V timing interval directly from the detected change in cardiac function.

130. The computer program product of claim 129, wherein the cardiac timing interval comprises a pacing interval.

131. The computer program product of claim 129, wherein the cardiac timing interval comprises an A-V timing interval.

132. The computer program product of claim 129, wherein the cardiac timing interval comprises a timing interval from a reference signal to a left ventricular stimulation and/or a timing interval from the reference signal to a right ventricular stimulation.