Evoked response variability as an indicator of autonomic tone and surrogate for patient condition

• US 6,711,439 B1
• Filed: 02/14/2002
• Issued: 03/23/2004
• Est. Priority Date: 02/14/2002
• Status: Active Grant

• Current Assignee: Pacesetter Incorporated (Abbott Laboratories Incorporated)
• Original Assignee: Pacesetter Incorporated (Abbott Laboratories Incorporated)
• Inventors: Bradley, Kerry, Park, Euljoon, Sloman, Laurence S.
• Primary Examiner(s): Getzow, Scott M.
• Application Number:
  US10/077,663
• Time in Patent Office: 768 Days
• Field of Search: 607/4-30
• US Class Current: 607/9
• CPC Class Codes: A61B 5/4035 Evaluating the autonomic nervous system
• CPC Class Codes: A61N 1/371 Capture, i.e. successful stimulation

Abstract

Modern implantable cardiac stimulation devices include processing and data storage capabilities that may be exploited to track myocardial condition and autonomic tone. Implantable devices have a capability to measure and store electrogram information over a period of time in a relatively large capacity memory, with advances in technology allowing increases in memory size. The evoked response varies in amplitude and morphology with changes in autonomic tone, ventricular filling, paced rate, and other parameters. The implantable cardiac device can be configured to sense and accurately quantify the evoked response, derive parameters from the quantified evoked response, store the parameters over long time periods, and derive variability statistics from the parameters to assist in tracking the patient'"'"'s condition over time, and guiding the patient'"'"'s therapy.

Claims

1. An implantable cardiac stimulation device comprising:

at least one pulse generator that is capable of generating stimulating pulses to stimulate cardiac tissue;

at least one sensor that is capable of electrical coupling to the cardiac tissue and sensing an evoked response resulting from an applied stimulating pulse;

a data storage array; and

a controller coupled to the at least one pulse generator, the at least one sensor, and the data storage array, the controller comprising an executable control logic that derives at least one parameter from the sensed evoked response, determines variation of the at least one parameter over time, and derives an indicator of patient condition based on the parameter variation.

2. An implantable cardiac stimulation device according to claim 1, wherein the controller monitors an amplitude of the evoked response over time as a surrogate of heart condition to detect progression or regression in heart failure patients.

3. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that tracks long-term changes in myocardial condition while filtering circadian and other extraneous influences on measurements comprising cardiac rate, exercise or activity level, and time of day.

4. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives an indicator of autonomic tone.

5. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives an indicator of myocardial condition.

6. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that adjusts a cardiac therapy based on the indicator of patient condition.

7. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives at least one parameter of parameters selected from among a group comprising evoked response amplitude, evoked response slope, evoked response integral, and evoked response time intervals.

8. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives frequency domain characteristics from the evoked response and derives at least one parameter of parameters selected from among a group comprising power spectral characteristics in a plurality of frequency bands, ratios between the power spectral characteristics in pairs of the plurality of frequency bands, evoked response amplitude, evoked response slope, evoked response integral, and evoked response time intervals.

9. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives at least one frequency domain characteristic parameter from the evoked response selected from among a group of frequency domain characteristic parameters comprising;

frequency domain parameters calculated from a single evoked response complex, frequency domain parameters calculated from an ensemble of averaged evoked response complexes, and frequency domain parameters calculated from a periodogram of stored intracardiac electrograms containing only evoked responses.

10. An implantable cardiac stimulation device according to claim 1 further comprising:

a timer coupled to the controller; and

an executable control logic operable in the controller that determines a time-to-zero-crossing parameter of a bipolar evoked response and a slope parameter of the bipolar evoked response, derives a parameter indicative of conduction velocity from the time-to-zero-crossing parameter and the slope parameter, and stores a time history of the time-to-zero-crossing parameter and the slope parameter as a metric for autonomic nervous system effects on myocardial state.

11. An implantable cardiac stimulation device according to claim 1 further comprising:

a timer coupled to the controller; and

an executable control logic operable in the controller that concurrently determines cardiac rate and AV/PV delay values for evoked cardiac cycles and stores the cardiac rate and AV/PV delay values in time correspondence with the time history of one or more of the parameters.

12. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives at least one variability statistic indicative of time variability of the parameter time history of one or more of the parameters and diagnostic of patient condition and adjusts a cardiac therapy based on one or more of the variability statistics.

13. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives at least one variability statistic indicative of time variability of the parameter time history of one or more of the parameters and diagnostic of patient condition and automatically adjusts aggressiveness of overdrive pacing based on one or more of the variability statistics.

14. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives at least one variability statistic indicative of time variability of the parameter time history of one or more of the parameters and diagnostic of patient condition and automatically adjusts pacing to lower circadian rates to promote intrinsic cardiac activity based on one or more of the variability statistics.

15. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that derives at least one variability statistic indicative of time variability of the parameter time history of one or more of the parameters and diagnostic of patient condition and automatically adjusts AV and PV delays to promote intrinsic cardiac activity based on one or more of the variability statistics.

16. An implantable cardiac stimulation device according to claim 1 wherein the evoked response is an atrial evoked response.

17. An implantable cardiac stimulation device according to claim 1 wherein the evoked response is a ventricular evoked response.

18. An implantable cardiac stimulation device according to claim 1 further comprising:

a telemetry transmitter and receiver coupled to the controller and capable of communicating an indicator of parameter variation to an external programmer.

19. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that controls an automatic capture functionality.

20. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that measures and tracks myocardial condition over time using a diurnal sensor that triggers a measurement at a consistent, suitable time at regular intervals such as one or more times per day or week.

21. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that acquires a 24-hour histogram of evoked response measurements and monitors daily change in autonomic tone is monitored by analysis of histogram characteristics such as width and tendency of the histogram at the same time of the day.

22. An implantable cardiac stimulation device according to claim 1 further comprising:

an executable control logic operable in the controller that performs cardiac physiology monitoring for controlling therapy, and operates as a control system for modifying stimulation rate to improve autonomic tone and enhance the evoked response.

23. An implantable cardiac stimulation device comprising:

at least one pulse generator that is capable of generating stimulation energy to be delivered to cardiac tissue;

at least one sensor that is capable of sensing an evoked response resulting from applied stimulation energy; and

a controller coupled to the at least one pulse generator and to the at least one sensor, the controller being operative to derive at least one parameter from the sensed evoked response, determine variation of the at least one parameter over time, and derive an indicator of patient condition based on the parameter variation.

24. A method of operating an implantable cardiac stimulation device comprising:

delivering stimulation energy to cardiac tissue;

sensing an evoked response of the cardiac tissue;

deriving at least one parameter from the evoked response;

determining variation of the at least one parameter over time; and

deriving an indicator of patient condition based on the parameter variation.

25. A method according to claim 24 further comprising:

adjusting a patient therapy based on the parameter variation.

26. A method according to claim 24 further comprising:

adjusting a cardiac therapy based on the parameter variation.

27. A method according to claim 24 further comprising:

communicating a derived parameter to an external programmer.

28. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of variation of the at least one parameter over time;

automatically diagnosing a patient condition from the at least one variability statistic; and

adjusting a cardiac therapy based on the patient condition and the at least one variability statistic.

29. A method according to claim 24 wherein:

deriving at least one parameter from the evoked response further comprises;

measuring an evoked response amplitude.

30. A method according to claim 24 wherein:

deriving at least one parameter from the evoked response further comprises;

measuring an evoked response slope.

31. A method according to claim 24 wherein deriving at least one parameter from the evoked response further comprises:

integrating the evoked response.

32. A method according to claim 24 wherein deriving at least one parameter from the evoked response further comprises:

timing at least one time interval in an evoked response signal sequence.

33. A method according to claim 24 wherein deriving at least one parameter from the evoked response further comprises:

acquiring a single evoked response complex; and

converting the single evoked response complex to a frequency domain signal.

34. A method according to claim 24 wherein deriving at least one parameter from the evoked response further comprises:

acquiring a plurality of evoked response complexes;

time aligning the plurality of evoked response complexes;

averaging the plurality of time aligned evoked response complexes to form an averaged evoked response signal; and

converting the averaged evoked response signal to a frequency domain signal.

35. A method according to claim 24 wherein deriving at least one parameter from the evoked response further comprises:

acquiring a plurality of intracardiac electrograms containing only evoked responses;

assembling the intracardiac electrograms into a periodogram; and

converting the periodogram to a frequency domain signal.

36. A method according to claim 24 wherein deriving at least one parameter from the evoked response further comprises:

acquiring a bipolar evoked response;

timing events of the bipolar evoked response;

determining a time-to-zero-crossing parameter of the bipolar evoked response;

determining a slope parameter of the bipolar evoked response;

deriving a parameter indicative of conduction velocity from the time-to-zero-crossing parameter and the slope parameter;

storing a time history of the time-to-zero-crossing parameter and the slope parameter as a metric for autonomic nervous system effects on myocardial state; and

deriving a variability statistic indicative of variation of the time-to-zero-crossing parameter and the slope parameter over time.

37. A method according to claim 24 wherein determining variation of the at least one parameter over time further comprises:

determining a cardiac rate and AV/PV interval values for evoked cardiac cycles;

storing the cardiac rate and AV/PV interval values in time correspondence with the parameters; and

correcting evoked response parameter variation for differences in cardiac rate and AV/PV interval.

38. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of time variability of the one or more parameters and diagnostic of patient condition; and

adjusting a cardiac therapy based on one or more of the variability statistics.

39. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of time variability of the one or more parameters and diagnostic of patient condition; and

adjusting aggressiveness of overdrive pacing based on one or more of the variability statistics without external intervention.

40. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of time variability of the one or more parameters and diagnostic of patient condition; and

adjusting pacing to lower circadian rates to promote intrinsic cardiac activity based on one or more of the variability statistics without external intervention.

41. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of time variability of the one or more parameters and diagnostic of patient condition; and

adjusting AV and PV delays to promote intrinsic cardiac activity based on one or more of the variability statistics without external intervention.

42. A method according to claim 24 further comprising:

determining a pharmacologic therapy based on the parameter variation.

43. A method according to claim 24 further comprising:

determining an electrical stimulation therapy based on the parameter variation.

44. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of time variability of the one or more parameters and diagnostic of patient condition; and

determining a pharmacologic therapy based on one or more of the variability statistics.

45. A method according to claim 24 further comprising:

deriving at least one variability statistic indicative of time variability of the one or more parameters and diagnostic of patient condition; and

determining an electrical stimulation therapy based on one or more of the variability statistics.

46. An implantable cardiac stimulation device comprising:

a pulse generator capable of coupling to cardiac tissue for stimulating an evoked response in the cardiac tissue;

a sensor capable of coupling to the cardiac tissue for sensing the evoked response;

a processor coupled to the pulse generator and coupled to the sensor;

a memory coupled to the processor and capable of storing data; and

executable means capable of execution in the processor for executing a sequence of actions further comprising;

means for deriving at least one parameter from the sensed evoked response;

means for determining variation of the at least one evoked response parameter over time; and

means for deriving an indicator of patient condition based on the parameter variation.

47. An implantable cardiac stimulation device according to claim 46 wherein the executable means further comprises:

adjusting means for adjusting a cardiac therapy based on the indicator of patient condition.

48. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for measuring an evoked response amplitude from the sensed evoked response.

49. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for determining an evoked response slope.

50. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for integrating the sensed evoked response to produce an evoked response integral.

51. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for determining one or more evoked response time intervals.

52. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for transforming the sensed evoked response to a frequency domain signal; and

means for determining power spectral characteristics of the frequency domain signal in a plurality of frequency bands.

53. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for transforming the sensed evoked response to a frequency domain signal;

means for determining power spectral characteristics of the frequency domain signal in a plurality of frequency bands; and

means for determining ratios between the power spectral characteristics in pairs of the plurality of frequency bands.

54. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for transforming a single evoked response complex to a frequency domain signal.

55. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for aligning the plurality of evoked response complexes in time;

means for averaging a plurality of evoked response complexes; and

means for transforming the averaged evoked response complex to a frequency domain signal.

56. An implantable cardiac stimulation device according to claim 46 wherein the evoked response parameter deriving means further comprises:

means for acquiring a plurality of intracardiac electrograms containing only evoked responses;

means for assembling the intracardiac electrograms into a periodogram; and

means for transforming the periodogram to a frequency domain signal.

57. An implantable cardiac stimulation device according to claim 46 further comprising:

a clock coupled to the processor for timing cardiac cycle events, wherein the evoked response parameter deriving means further comprises;

means for timing a time-to-zero-crossing parameter of a bipolar evoked response;

means for determining a slope parameter of the bipolar evoked response;

means for deriving a parameter indicative of conduction velocity from the time-to-zero-crossing parameter and the slope parameter; and

means for tracking time variations in the time-to-zero-crossing parameter and the slope parameter as a metric for autonomic nervous system effects on myocardial state.

58. An implantable cardiac stimulation device according to claim 46 further comprising:

a clock coupled to the processor for timing cardiac cycle events, wherein the evoked response parameter deriving means further comprises;

means for concurrently determining cardiac rate and AV/PV delay values for evoked cardiac cycles; and

means for time correlating the cardiac rate and AV/PV delay values with the one or more evoked response parameters.

59. An implantable cardiac stimulation device according to claim 46 wherein the executable means further comprises:

variability deriving means for deriving at least one variability statistic indicative of variation of the at least one evoked response parameter over time; and

means for adjusting a cardiac therapy based on one or more of the variability statistics.

60. An implantable cardiac stimulation device according to claim 46 wherein the executable means further comprises:

variability deriving means for deriving at least one variability statistic indicative of variation of the at least one evoked response parameter over time; and

means for adjusting aggressiveness of overdrive pacing based on one or more of the variability statistics without external intervention.

61. An implantable cardiac stimulation device according to claim 46 wherein the executable means further comprises:

variability deriving means for deriving at least one variability statistic indicative of variation of the at least one evoked response parameter over time; and

means for adjusting pacing to lower circadian rates to promote intrinsic cardiac activity based on one or more of the variability statistics without external intervention.

62. An implantable cardiac stimulation device according to claim 46 wherein the executable means further comprises:

variability deriving means for deriving at least one variability statistic indicative of variation of the at least one evoked response parameter over time; and

means for adjusting AV and PV delays to promote intrinsic cardiac activity based on one or more of the variability statistics without external intervention.

63. An implantable cardiac stimulation device according to claim 46 further comprising:

an atrial pulse generator for stimulating an evoked response in atrial cardiac tissue;

atrial sensor capable of coupling to the atrial cardiac tissue for sensing the atrial evoked response.

64. An implantable cardiac stimulation device according to claim 46 further comprising:

ventricular pulse generator for stimulating an evoked response in ventricular cardiac tissue;

ventricular sensor capable of coupling to the ventricular cardiac tissue for sensing the ventricular evoked response.

65. An implantable cardiac stimulation device according to claim 46 further comprising:

telemetry means coupled to the execution means for communicating one or more of the parameters to an external programmer.

66. An implantable cardiac stimulation comprising:

means for providing stimulation energy to cardiac tissue;

means for deriving at least one parameter from an evoked response signal;

means for determining a variation of the at least one parameter over time; and

means for deriving an indicator of patient condition based on the parameter variation.