Method and system for evaluating cardiac ischemia with RR-interval data sets

• US 6,652,467 B2
• Filed: 06/26/2001
• Issued: 11/25/2003
• Est. Priority Date: 06/26/2000
• Status: Expired due to Fees

• Current Assignee: Mediwave Star Technology Incorporated
• Original Assignee: Mediwave Star Technology Incorporated
• Inventors: Starobin, Joseph M., Chernyak, Yuri B.
• Primary Examiner(s): EVANISKO, GEORGE ROBERT
• Application Number:
  US09/891,910
• Publication Number:
  US 20020042578A1
• Time in Patent Office: 882 Days
• Field of Search: 600/508-510, 600/515-521
• US Class Current: 600/508
• CPC Class Codes: A61B 5/02405 Determining heart rate variability
• CPC Class Codes: A61B 5/0245 by using sensing means generating electric signals, i.e. ECG signals
• CPC Class Codes: A61B 5/349 Detecting specific parameters of the electrocardiograph cycle
• CPC Class Codes: A61B 5/352 Detecting R peaks, e.g. for synchronising diagnostic apparatus; Estimating R-R interval
• CPC Class Codes: A61B 5/36 Detecting PQ interval, PR interval or QT interval
• CPC Class Codes: A61B 5/366 Detecting abnormal QRS complex, e.g. widening

Abstract

A method of assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject is described herein. The method comprises the steps of: (a) collecting a first RR-interval data set from the subject during a stage of gradually increasing heart rate (e.g., a stage of gradually increasing exercise load); (b) collecting a second RR-interval data set from the subject during a stage of gradually decreasing heart rate (e.g., a stage of gradually decreasing exercise load); (c) comparing the first RR-interval data set to the second RR-interval data set to determine the difference between the data sets; and (d) generating from the comparison of step (c) a measure of cardiac ischemia during exercise in the subject. A greater difference between the first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in the subject. The data sets are collected in such a manner that they reflect almost exclusively the conduction in the heart muscle and minimize the effect on the data sets of rapid transients due to autonomic nervous system and hormonal control.

Claims

1. A method of assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject, said method comprising the steps of:

(a) collecting a first RR-interval data set from said subject during a stage of gradually increasing heart rate;

(b) collecting a second RR-interval data set from said subject during a stage of gradually decreasing heart rate, with said first and second RR-interval data sets being collected while minimizing the influence of rapid transients due to autonomic nervous system and hormonal influence on said data sets;

(c) comparing said first RR-interval data set to said second RR-interval data set to determine the difference between said data sets; and

(d) generating from said comparison of step (c) a measure of cardiac ischemia in said subject, wherein a greater difference between said first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in said subject.

2. The method according to claim 1, wherein said first and second RR-interval data sets are collected under quasi-stationary conditions.

3. The method according to claim 1, wherein said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are each at least 3 minutes in duration.

4. The method according to claim 1, wherein said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are together carried out for a total time of from 6 minutes to 40 minutes.

5. The method according to claim 1, wherein:

both said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are carried out between a peak rate and a minimum rate; and

said peak rates of both said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are the same.

6. The method according to claim 5, wherein:

said minimum rates of both said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are substantially the same.

7. The method according to claim 1, wherein said stage of gradually decreasing heart rate is carried out at at least three different heart-rate stimulation levels.

8. The method according to claim 7, wherein said stage of gradually increasing heart rate is carried out at at least three different heart-rate stimulation levels.

9. The method according to claim 1, wherein said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are carried out sequentially in time.

10. The method according to claim 1, wherein said comparing step is carried out by generating curves from each of said data sets.

11. The method according to claim 10, wherein said comparing step is carried out by comparing the shapes of said curves from data sets.

12. The method according to claim 10, wherein said comparing step is carried out by determining a measure of the domain between said curves.

13. The method according to claim 10, wherein said comparing step is carried out by both comparing the shapes of said curves from data sets and determining a measure of the domain between said curves.

14. The method according to claim 10, further comprising the step of displaying said curves.

15. The method according to claim 1, wherein said heart rate during said stage of gradually increasing heart rate does not exceed more than 120 beats per minute.

16. The method according to claim 1, wherein said heart rate during said stage of gradually increasing heart rate exceeds 120 beats per minute.

17. The method according to claim 1, further comprising the step of:

(e) comparing said measure of cardiac ischemia during stimulation to at least one reference value; and

then

(f) generating from said comparison of step (e) a quantitative indicium of cardiac or cardiovascular health for said subject.

18. The method according to claim 17, further comprising the steps of:

(g) treating said subject with a cardiovascular therapy; and

then

(h) repeating steps (a) through (f) to assess the efficacy of said cardiovascular therapy, in which a decrease in the difference between said data sets from before said therapy to after said therapy indicates an improvement in cardiac health in said subject from said cardiovascular therapy.

19. The method according to claim 18, wherein said cardiovascular therapy is selected from the group consisting of aerobic exercise, muscle strength building, change in diet, nutritional supplement, weight loss, stress reduction, smoking cessation, pharmaceutical treatment, surgical treatment, and combinations thereof.

20. The method according to claim 17, further comprising the step of assessing from said quantitative indicum the likelihood that said subject is at risk to experience a future ischemia-related cardiac incident.

29. The method according to claim 20, wherein said comparing step is carried out by generating curves from each of said data sets.

30. The method according to claim 29, wherein said comparing step is carried out by comparing the shapes of said curves from said data sets.

31. The method according to claim 29, wherein said comparing step is carried out by determining a measure of the domain between said curves.

32. The method according to claim 29, wherein said comparing step is carried out by both comparing the shapes of said curves from data sets and determining a measure of the domain between said curves.

33. The method according to claim 29, further comprising the step of displaying said curves.

34. The method according to claim 20, wherein said heart rate during said stage of gradually increasing exercise load does not exceed more than 120 beats per minute.

35. The method according to claim 20, said heart rate during said stage of gradually increasing heart rate exceeds 120 beats per minute.

36. The method according to claim 20, further comprising the step of:

(e) comparing said measure of cardiac ischemia during exercise to at least one reference value; and

then

(f) generating from said comparison of step (e) a quantitative indicium of cardiac or cardiovascular health for said subject.

37. The method according to claim 36, further comprising the steps of:

(g) treating said subject with a cardiovascular therapy; and

then

(h) repeating steps (a) through (f) to assess the efficacy of said cardiovascular therapy, in which a decrease in the difference between said data sets from before said therapy to after said therapy indicates an improvement in cardiac or cardiovascular health in said subject from said cardiovascular therapy.

38. The method according to claim 37, wherein said cardiovascular therapy is selected from the group consisting of aerobic exercise, muscle strength building, change in diet, nutritional supplement, weight loss, stress reduction, smoking cessation, pharmaceutical treatment, and combinations thereof.

39. The method according to claim 36, further comprising the step of assessing from said quantitative indicium the likelihood that said subject is at risk to experience a future ischemia-related cardiac incident.

21. A method of assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject, said method comprising the steps of:

(a) collecting a first RR-interval data set from said subject during a stage of gradually increasing exercise load and gradually increasing heart rate; and

then, without an intervening rest stage,

(b) collecting a second RR-interval data set from said subject during a stage of gradually decreasing exercise load and gradually decreasing heart rate;

(c) comparing said first RR-interval data set to said second RR-interval data set to determine the difference between said data sets; and

(d) generating from said comparison of step (c) a measure of cardiac ischemia during exercise in said subject, wherein a greater difference between said first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in said subject.

22. The method according to claim 21, wherein said stage of gradually increasing exercise load and gradually decreasing exercise load are each at least 3 minutes in duration.

23. The method according to claim 21, wherein said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are together carried out for a total time of from 6 minutes to 40 minutes.

24. The method according to claim 21, wherein:

both said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are carried out between a peak load and a minimum load; and

said peak loads of both said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are essentially the same.

25. The method according to claim 24, wherein:

said minimum loads of both said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are essentially the same.

26. The method according to claim 21, wherein said stage of gradually decreasing exercise load is carried out at at least three different load levels.

27. The method according to claim 21, wherein said stage of gradually increasing exercise load is carried out at at least three different load levels.

28. The method according to claim 21, wherein said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are carried out sequentially in time.

40. A method of assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject, said method comprising the steps of:

(a) collecting a first RR-interval data set from said subject during a stage of gradually increasing exercise load and gradually increasing heart rate at least 5 minutes in duration, and at at least three different load levels; and

then, without an intervening rest stage,

(b) collecting a second RR-interval data set from said subject during a stage of gradually decreasing exercise load and gradually decreasing heart rate at least 5 minutes in duration, and at at least three different load levels;

(c) comparing said first RR-interval data set to said second RR-interval data set to determine the difference between said data sets;

(d) generating from said comparison of step (c) a measure of cardiac ischemia during exercise in said subject, wherein a greater difference between said first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in said subject;

(e) comparing said measure of cardiac ischemia during exercise to at least one reference value; and

then

(f) generating from said comparison of step (e) a quantitative indicium of cardiac or cardiovascular health for said subject.

41. The method according to claim 40, wherein said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are together carried out for a total time of from 6 minutes to 40 minutes.

42. The method according to claim 40, wherein:

both said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are carried out between a peak load and a minimum load; and

said peak loads of both said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are essentially the same.

43. The method according to claim 42, wherein:

said minimum loads of both said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are essentially the same.

44. The method according to claim 40, wherein said stage of gradually increasing exercise load and said stage of gradually decreasing exercise load are carried out sequentially and contiguously in time.

45. The method according to claim 40, wherein said generating comparing step is carried out by generating curves from each of said data sets.

46. The method according to claim 45, wherein said comparing step is carried out by comparing the shapes of said curves from said data sets.

47. The method according to claim 45, wherein said comparing step is carried out by determining a measure of the domain between said curves.

48. The method according to claim 45, wherein said comparing step is carried out by both comparing the shapes of said curves from said data sets and determining a measure of the domain between said curves.

49. The method according to claim 45, further comprising the step of displaying said curves.

50. The method according to claim 40, wherein said heart rate during said stage of gradually increasing exercise load does not exceed more than 120 beats per minute.

51. The method according to claim 40, wherein said heart rate during said stage of gradually increasing heart rate exceeds 120 beats per minute.

52. The method according to claim 40, comprising the steps of:

(g) treating said subject with a cardiovascular therapy; and

then

(h) repeating steps (a) through (f) to assess the efficacy of said cardiovascular therapy, in which a decrease in the difference between said data sets from before said therapy to after said therapy indicates an improvement in cardiac or cardiovascular health in said subject from said cardiovascular therapy.

53. The method according to claim 52, wherein said cardiovascular therapy is selected from the group consisting of aerobic exercise, muscle strength building, change in diet, nutritional supplement, weight loss, stress reduction, smoking cessation, pharmaceutical treatment, surgical treatment, and combinations thereof.

54. The method according to claim 40, further comprising the step of assessing from said quantitative indicium the likelihood that said subject is at risk to experience a future ischemia-related cardiac incident.

55. A method of assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject, said method comprising the steps of:

(a) collecting a first RR-interval data set from said subject during a stage of gradually increasing heart rate, said heart rate being gradually increased in response to actual heart rate data collected from concurrent monitoring of said patient;

(b) collecting a second RR-interval data set from said subject during a stage of gradually decreasing heart rate, said heart rate being gradually decreased in response to actual heart rate data collected from concurrent monitoring of said patient;

(c) comparing said first RR-interval data set to said second RR-interval data set to determine the difference between said data sets; and

(d) generating from said comparison of step (c) a measure of cardiac ischemia in said subject, wherein a greater difference between said first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in said subject.

56. The method according to claim 55, wherein said first and second RR-interval data sets are collected without intervening rest period.

57. The method according to claim 55, wherein said stage of gradually increasing heart rate and gradually decreasing heart rate are each at least 3 minutes in duration.

58. The method according to claim 55, wherein said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are together collected for a total time of from 6 minutes to 40 minutes.

59. The method according to claim 55, wherein:

both said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are carried out between a peak rate and a minimum rate; and

said peak rates of both said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are substantially the same.

60. The method according to claim 59, wherein:

said minimum rates of both said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are the same.

61. The method according to claim 55, wherein said stage of gradually decreasing heart rate is collected at at least three different heart-rate levels.

62. The method according to claim 61, wherein said stage of gradually increasing heart rate is collected at at least three different heart-rate levels.

63. The method according to claim 55, wherein said stage of gradually increasing heart rate and said stage of gradually decreasing heart rate are carried out sequentially in time.

64. The method according to claim 55, wherein said comparing step is carried out by generating curves from each of said data sets.

65. The method according to claim 64, wherein said comparing step is carried out by comparing the shapes of said curves from said data sets.

66. The method according to claim 64, wherein said comparing step is carried out by determining a measure of the domain between said curves.

67. The method according to claim 64, wherein said comparing step is carried out by both comparing the shapes of said curves from said data sets and determining a measure of the domain between said curves.

68. The method according to claim 64, further comprising the step of displaying said curves.

69. The method according to claim 55, wherein said heart rate during said stage of gradually increasing heart rate does not exceed more than 120 beats per minute.

70. The method according to claim 55, wherein said heart rate during said stage of gradually increasing heart rate exceeds 120 beats per minute.

71. The method according to claim 55, comprising the step of:

(e) comparing said measure of cardiac ischemia during stimulation to at least one reference value; and

then

(f) generating from said comparison of step (e) a quantitative indicium of cardiac or cardiovascular health for said subject.

72. The method according to claim 70, further comprising the steps of:

(g) treating said subject with a cardiovascular therapy; and

then

(h) repeating steps (a) through (f) to assess the efficacy of said cardiovascular therapy, in which a decrease in the difference between said data sets from before said therapy to after said therapy indicates an improvement in cardiac or cardiovascular health in said subject from said cardiovascular therapy.

73. The method according to claim 72, said cardiovascular therapy is selected from the group consisting of aerobic exercise, muscle strength building, change in diet, nutritional supplement, weight loss, stress reduction, smoking cessation, pharmaceutical treatment, surgical treatment, and combinations thereof.

74. The method according to claim 71, further comprising the step of assessing from said quantitative indicium the likelihood that said subject is at risk to experience a future ischemia-related cardiac incident.

75. A method of assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject, said method comprising performing on a computer the steps of:

(a) providing a first RR-interval data set collected from said subject during a stage of gradually increasing heart rate;

(b) providing a second RR-interval data set collected from said subject during a stage of gradually decreasing heart rate;

(c) comparing said first RR-interval data set to said second RR-interval data set to determine the difference between said data sets; and

(d) generating from said comparison of step (c) a measure of cardiac ischemia in said subject, wherein a greater difference between said first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in said subject.

76. The method according to claim 75, wherein said first and second RR-interval data sets are collected while minimizing the influence of rapid transients due to autonomic nervous system and hormonal control on said data sets.

77. The method according to claim 75, wherein said first and second RR-interval data sets are collected without an intervening rest stage.

78. The method according to claim 75, wherein said comparing step is carried out by generating curves from each of said data sets.

79. The method according to claim 78, wherein said comparing step is carried out by comparing the shapes of said curves from data sets.

80. The method according to claim 78, wherein said comparing step is carried out by determining a measure of the domain between said curves.

81. The method according to claim 78, wherein said comparing step is carried out by both comparing the shapes of said curves from data sets and determining a measure of the domain between said curves.

82. The method according to claim 78, further comprising the step of displaying said curves.

83. The method according to claim 75, wherein said comparing step is carried out by:

(i) filtering said first and second RR-interval data sets;

(ii) generating a smoothed hysteresis loop from said filtered first and second RR-interval data sets; and

then

(iii) determining the domain of said smoothed hysteresis loop.

84. The method according to claim 75, wherein said comparing step is carried out by:

(i) filtering said first and second RR-interval data sets;

(ii) generating preliminary minima values for said first and second RR-interval data sets;

(iii) correcting said preliminary minima values;

(iv) generating first and second preliminary smoothed curves from each of said filtered data sets;

(v) correcting said preliminary smoothed curves;

(vi) fitting said preliminary smoothed curves;

(vii) generating a smoothed hysteresis loop from said first and second fitted smoothed curves; and

then

(viii) determining the domain of said hysteresis loop.

85. The method according to claim 75, wherein said comparing step is carried out by:

(i) filtering said first and second RR-interval data sets by moving average smoothing;

(ii) generating a smoothed hysteresis loop from said filtered first and second RR-interval data sets; and

then

(iii) determining the domain of said hysteresis loop.

86. The method according to claim 75, wherein said comparing step is carried out by

(i) sequentially combining said first and second RR-interval data sets into one combined RR-interval set;

(ii) filtering said combined RR-interval data sets;

(iii) evaluating coordinates of the minima of said combined and filtered RR-interval data set;

(iv) defining central data subsets including the minima of said combined and filtered RR-interval data set;

(v) fitting each said central data subset with a parabola that has a minimum inside said data subset;

(vi) determining coordinates of the minimum for each said parabola;

(vii) defining reduced data subsets by excluding said central data sets from said combined and filtered RR-interval data set;

(viii) generating a first transformed RR-interval data set by mapping falling off branches of said reduced data sets by a standard monotonously decreasing mapping function of RR-intervals, which depends on at least one discrete or continuous parameter;

(ix) generating a second transformed RR-interval data set by mapping growing branches of said reduced data sets by a standard monotonously increasing mapping function of RR-intervals, which depends on at least one discrete or continuous parameter;

(x) fitting said first and second transformed sets by a standard function of time depending on one or more parameters whose values are determined by the condition of the best fit;

(xi) completing said fitting step by determining the parameters of said mapping functions of RR-intervals by the condition of the best fit for each branch of said RR-interval data set;

(xii) generating a hysteresis loop from said best fit functions; and

then

(xiii) evaluating a measure of the domain inside said hysteresis loop.

87. A computer system for assessing cardiac ischemia in a subject to provide a measure of cardiac or cardiovascular health in that subject, said system comprising:

(a) means for providing a first RR-interval data set from said subject during a stage of gradually increasing heart rate;

(b) means for providing a second RR-interval data set from said subject during a stage of gradually decreasing heart rate;

(c) means for comparing said first RR-interval data set to said second RR-interval data set to determine the difference between said data sets; and

(d) means for generating from said comparison a measure of cardiac isehemia in said subject, wherein a greater difference between said first and second data sets indicates greater cardiac ischemia and lesser cardiac or cardiovascular health in said subject;

(e) means for comparing the measure of cardiac ischemia to at least one reference value; and

(f) means for generating at least one quantitative indicium of cardiovascular health for said subject.

88. The system according to claim 87, wherein said means for comparing further comprises means for generating curves from each of said data sets.

89. The system according to claim 87, wherein said means for comparing further comprises means for comparing the shapes of said curves from data sets.

90. The system according to claim 87, wherein said means for comparing further comprises means for determining a measure of the domain between said curves.

91. The system according to claim 87, wherein said means for comparing further comprises means for both comparing the shapes of said curves from data sets and determining a measure of the domain between said curves.