Cardiac electromechanics - Patent Review 5738096

I claim:

1. A method of constructing a map of the heart having a heart cycle comprising:

(a) bringing a probe into contact with a location on a wall of the heart;

(b) determining a position of the probe at the location;

(c) repeating (a) and (b) for a multiplicity of locations of the heart; and

(d) combining the determined positions of the probe to determine a structural map of at least a portion of the heart.

2. A method according to claim 1 comprising determining local pathologies in the heart based on the map.

3. A method according to claim 1 and comprising determining at least a second position of the probe at a phase of the cycle different from the phase at the position determination of (b) and wherein the map is a phase dependent geometric map.

4. A method according to claim 3, wherein the second position determination is performed at the location.

5. A method according to claim 4 comprising analyzing the map to determine underutilized portions of the heart.

6. A method according to claim 4 comprising analyzing the map to determine procedures for improving the operation of the heart.

7. A method according to claim 4 comprising, determining a local change in the geometry of the heart.

8. A method according to claim 7 comprising determining local pathologies in the heart based on the local changes in geometry.

9. A method according to claim 7, wherein the local change comprises a change in a local radius of the heart wall at the location.

10. A method according to claim 9 comprising determining an intra-cardiac pressure of the heart.

11. A method according to claim 10 comprising determining a tension of the heart at the location by applying Laplace's law to the change in the local radius and the determined pressure.

12. A method according to claim 9, further comprising determining a relative tension of the heart at the location by applying Laplace's law to the change in the local radius.

13. A method according to claim 4 comprising determining the activity of the heart at the location.

14. A method according to claim 13, wherein determining the activity comprises determining a relative motion profile of the location on the heart wall relative to neighboring locations.

15. A method according to claim 14 comprising determining local pathologies in the heart based on the relative motion profile.

16. A method according to claim 13, wherein determining the activity comprises determining a motion profile of the heart at the location.

17. A method according to claim 16 comprising determining local pathologies in the heart based on the motion profile.

18. A method according to claim 16 comprising monitoring the stability of the contact between the probe and the heart based on the motion profile.

19. A method according to claim 18, wherein monitoring comprises detecting changes in the motion profile for different heart cycles.

20. A method according to claim 18, wherein monitoring comprises detecting differences in positions of the probe at the same phase for different heart cycles.

21. A method according to claim 4 comprising binning positions according to characteristics of the heart cycle.

22. A method according to claim 21 comprising separately combining the information in each bin into a map.

23. A method according to claim 22 comprising determining differences between the maps.

24. A method according to claim 23 comprising determining local pathologies in the heart based on the determined differences between maps.

25. A method according to claim 21, wherein the characteristics comprise a heart rate.

26. A method according to claim 21, wherein the characteristics comprise a morphology of an ECG of the heart.

27. A method according to claim 1 comprising determining local information at the location at which the position of the probe is determined and wherein combining the positions comprises combining the positions and the local information to form a map incorporating the local information.

28. A method according to claim 27 comprising, analyzing the map to determine overstressed portions of the heart.

29. A method according to claim 27, wherein the local information is determined using a sensor not mounted on the probe.

30. A method according to claim 27, wherein the local information is determined using a sensor external to the body.

31. A method according to claim 27, wherein the local information is determined using a sensor on the probe.

32. A method according to claim 27, wherein the local information and the position of the probe are determined at substantially the same time.

33. A method according to claim 27, wherein the local information and the position of the probe are determined at substantially different times.

34. A method according to claim 27 comprising determining a relationship between changes in positions of the probe and determined local information at at least one location.

35. A method according to claim 34 comprising determining local pathologies in the heart based on the at least one local relationship.

36. A method according to claim 27, wherein the local information comprises a chemical concentration value.

37. A method according to claim 27, wherein the local information comprises a thickness of the heart at the location.

38. A method according to claim 37, wherein the thickness of the heart is determined using an ultrasonic transducer mounted on the probe.

39. A method according to claim 27, wherein the local information comprises a measure of a perfusion of the heart at the location.

40. A method according to claim 27, wherein the local information comprises a measure of the work performed by the heart portion at the location.

41. A method according to claim 27, wherein the local information comprises local electrical activity.

42. A method according to claim 41, wherein the electrical activity comprises a local electrogram.

43. A method according to claim 41, wherein the electrical activity comprises a local activation time.

44. A method according to claim 41, wherein the electrical activity comprises a local plateau duration of heart tissue at the location.

45. A method according to claim 27, wherein the probe is located in a coronary vein or artery.

46. A method according to claim 27, wherein the probe is located outside a blood vessel.

47. A method according to claim 1 comprising determining local information at at least two phases of the heart cycle at a location and wherein combining the positions comprises combining the positions and the local information to form a map comprising phase dependent local information.

48. A method according to claim 47 comprising analyzing changes in the determined local information.

49. A method according to claim 48 comprising determining local pathologies in the heart based on the changes in the local information.

50. A method according to claim 49, wherein the changes are a function of the heart cycle and further comprising determining the phase of the heart cycle at which the local information is determined.

51. A method according to claim 49, comprising determining local electrical activity at the location and wherein the changes are related to local electrical activity at the location.

52. A method according to claim 47 comprising analyzing the map to determine underutilized portions of the heart.

53. A method according to claim 47 comprising analyzing the map to determine procedures for improving the operation of the heart.

54. A method according to claim 47, wherein the local information comprises a thickness of the heart, and further comprising determining a reaction of the heart to an activation signal by analyzing changes in the thickness of the heart.

55. A method according to claim 47, further comprising binning local information according to characteristics of the heart cycle.

56. A method according to claim 55, wherein the characteristics comprise a heart rate.

57. A method according to claim 55, wherein the characteristics comprise a morphology of an ECG of the heart.

58. A method according to claim 1, further comprising reconstructing a surface portion of the heart.

59. A method according to claim 58 comprising determining local pathologies in the heart based on the reconstructed surface portion.

60. A method according to claim 1, wherein the positions of the probe are positions determined relative to a reference location.

61. A method according to claim 60, wherein the reference location is a predetermined portion of the heart.

62. A method according to claim 60, wherein a position of the reference location is determined using a position sensor.

63. A method according to claim 60, comprising periodically determining a position of the reference location.

64. A method according to claim 63, wherein the position of the reference location is acquired at the same phase of consecutive cardiac cycles.

65. A method according to claim 1, wherein the probe is located in a coronary vein or artery.

66. A method according to claim 1, wherein the probe is located outside a blood vessel.

67. A method of determining the structure of at least a portion of a heart having a heart cycle comprising:

(a) bringing a probe into contact with a location on a wall of the heart;

(b) determining a position in space of the probe at the location;

(c) acquiring data at the position in space;

(d) repeating (a), (b) and (c) for a multiplicity of locations of the heart to determine a multiplicity of data each associated with a determined position of the probe in space; and

(e) combining the multiplicity of the data and the determined positions of the probe in space to determine a map, containing said data, of at least a portion of the heart, said positions in space being determined solely from information other than that derived from an image of the vicinity of the probe at the locations.

68. A method according to claim 67 wherein the map is a phase dependent map of said data.

69. A method according to claim 67 wherein the data comprises local chemical concentration values and wherein the map comprises a map of said chemical concentration values.

70. A method according to claim 67 wherein said data comprises the thickness of the heart at said locations and wherein the map comprises a map of thickness of the heart.

71. A method according to claim 67 wherein the data comprises local perfusion of the heart at at least some of said locations and wherein the map comprises a perfusion map of at least a portion of the heart.

72. A method according to claim 67 wherein the data is used to determine local work performed at at least some of said locations and wherein the map comprises a map of the work performed at locations of the heart.

73. A method according to claim 67 wherein the data comprises electrical activity at at least some of the locations and wherein the map comprises a map of local electrical activity.

74. A method according to claim 67 wherein the data comprises local activation time at at least some of the locations and wherein the map comprises a map of local activation time.

75. A method according to claim 67 wherein the data is utilized to determine a local plateau duration at a plurality of locations and wherein the map comprises a map of local plateau duration.

76. A method according to claim 67 wherein the positions are determined with respect to a reference location.

77. A method according to claim 76 wherein the reference location is a location which is fixed in the moving heart.

78. A method according to claim 77 wherein the position in space of the reference location is determined using a position sensor.

79. A method of performing measurements of a heart having a heart cycle comprising:

(a) bringing a probe into contact with a location on a wall of the heart;

(b) determining a first position in space of the probe at the location for a first phase of the heart;

(c) repeating (b) at the location, for a second phase of the heart, to determine a second position of the probe in space; and

(d) calculating the movement of the heart at the location utilizing the first and second determined positions of the probe in space.

80. A method according to claim 79 wherein the positions are determined with respect to a reference location.

81. A method according to claim 80 wherein the reference location is a location which is fixed in the moving heart.

82. A method according to claim 79 and including repeating steps (a) to (d) for a multiplicity of different locations on the heart.

83. A method according to claim 82 and including mapping the determined motions of the heart at different locations to generate a map of heart wall motion for at least a portion of the heart.

84. A method according to claim 82 wherein the position in space of the probe is determined using a position sensor.

85. A method of determining the structure of at least a portion of a heart having a heart cycle comprising:

(a) bringing a probe into contact with a location on a wall of the heart;

(b) determining a position in space of the probe at the location;

(c) acquiring data at the position of the probe in space;

(d) repeating (a), (b) and (c) for a multiplicity of locations of the heart to determine a multiplicity of data each associated with a determined position of the probe in space; and

(e) combining the multiplicity of the data and the determined positions of the probe in space to determine a map of at least a portion of the heart containing said data, without utilizing, prior to or during said combining, an image of the heart other than one reconstructed from the determined positions of the probe in space.

86. A method according to claim 85 wherein the map is a phase dependent map of said data.

87. A method according to claim 85 wherein the data comprises local chemical concentration values and wherein the map comprises a map of said chemical concentration values.

88. A method according to claim 85 wherein said data comprises the thickness of the heart at said locations and wherein the map comprises a map of thickness of the heart.

89. A method according to claim 85 wherein the data comprises local perfusion of the heart at at least some of said locations and wherein the map comprises a perfusion map of at least a portion of the heart.

90. A method according to claim 85 wherein the data is used to determine local work performed at at least some of said locations and wherein the map comprises a map of the work performed at locations of the heart.

91. A method according to claim 85 wherein the data comprises electrical activity at at least some of the locations and wherein the map comprises a map of local electrical activity.

92. A method according to claim 85 wherein the data comprises local activation time at at least some of the locations and wherein the map comprises a map of local activation time.

93. A method according to claim 85 wherein the data is utilized to determine a local plateau duration at a plurality of locations wherein the map comprises a map of local plateau duration.

94. A method according to claim 85 wherein the positions are determined with respect to a reference location.

95. A method according to claim 94 wherein the reference location is a location which is fixed in the moving heart.

96. A method according to claim 95 wherein the position in space of the reference location is determined using a position sensor.

97. Apparatus for constructing a map of the heart having a heart cycle comprising:

a probe, having a distal end and adapted for contact of the distal end with a location on the inner heart wall;

means for determining the position in space of the distal end of the probe at the location; and

computing circuitry which combines a multiplicity of positions of the distal end of the probe in space determined at different locations on the heart to form a structural map of at least a portion of the heart.

98. Apparatus according to claim 97 wherein the probe has a position sensor located adjacent the distal end wherein the means for determining the position determines the position based on a determination of the position of the position sensor.

99. Apparatus according to claim 97 and including means for determining contact of the probe during said position determination.

100. Apparatus according to claim 97 wherein the means for determining the position of the distal end of the probe comprises means for determining the position of the distal end of the probe with respect to a reference location.

101. Apparatus according to claim 100 wherein the means for determining the position of the distal end of the probe with respect to a reference location comprises means for determining the position of a reference location fixed in the moving heart.

102. Apparatus according to claim 101 wherein the means for determining the position of a reference location fixed in the moving heart comprises a position sensor placed at the reference location.

103. Apparatus for performing measurements of a heart having a heart cycle, the apparatus comprising:

a probe, having a distal end and adapted for contact of the distal end with a location on the inner heart wall;

means for determining the position in space of the distal end of the probe at the location; and

computing circuitry which combines a multiplicity of positions in space of the distal end of the probe determined at different locations on the heart to form a map without utilizing an image of a region surrounding the distal end of the probe at the position.

104. Apparatus according to claim 103 wherein the probe has a position sensor located adjacent the distal end wherein the means for determining the position determines the position based on a determination of the position of the position sensor.

105. Apparatus according to claim 103 and including means for determining contact of the probe during said position determination.

106. Apparatus according to claim 103 wherein the map is a structural map of at least a portion of the heart.

107. Apparatus according to claim 103 wherein the means for determining the position of the distal end of the probe comprises means for determining the position of the distal end of the probe with respect to a reference location.

108. Apparatus according to claim 107 wherein the means for determining the position of the distal end of the probe with respect to a reference location comprises means for determining the position of a reference location fixed in the moving heart.

109. Apparatus according to claim 108 wherein the means for determining the position of a reference location fixed in the moving heart comprises a position sensor placed at the reference location.

110. Apparatus for performing measurements of a heart having a heart cycle, the apparatus comprising:

a probe, having a distal end and adapted for contact of the distal end with a location on the heart wall;

means for determining the position in space of the distal end of the probe at the location; and

computing circuitry which combines a plurality of positions of the distal end of the probe in space, determined at a particular location for a plurality of cycles of the heart.

111. Apparatus according to claim 110 wherein the plurality of positions are combined by the computing circuitry to determine the movement of the heart wall at the location.

112. Apparatus according to claim 111 wherein the computing circuitry combines a plurality of determined movements at different locations of the heart wall to form a map of heart wall movement.

113. Apparatus according to claim 110 wherein the means for determining the position of the distal end of the probe comprises means for determining the position of the distal end of the probe with respect to a reference location.

114. Apparatus according to claim 113 wherein the means for determining the position of the distal end of the probe with respect to a reference location comprises means for determining the position of a reference location fixed in the moving heart.

115. Apparatus according to claim 114 wherein the means for determining the position of a reference location fixed in the moving heart comprises a position sensor placed at the reference location.

116. Apparatus for performing measurements of a heart having a heart cycle, the apparatus comprising:

a probe, having a distal end and adapted for contact of the distal end with a location on the inner heart wall;

means for determining the position in space of the distal end at the location;

means for determining local information at the location, referenced to the position of the distal end in space; and

computing circuitry which combines the multiplicity of the data and the determined positions of the probe in space to determine a map, containing said data, of at least a portion of the heart, without utilizing, prior to or during said combining, an image of the heart other than one reconstructed from the determined positions.

117. Apparatus according to claim 116 wherein the means for determining the position of the distal end of the probe comprises means for determining the position of the distal end of the probe with respect to a reference location.

118. Apparatus according to claim 117 wherein the means for determining the position of the distal end of the probe with respect to a reference location comprises means for determining the position of a reference location fixed in the moving heart.

119. Apparatus according to claim 118 wherein the means for determining the position of a reference location fixed in the moving heart comprises a position sensor placed at the reference location.

Description Submit all comments and votes

FIELD OF THE INVENTION

The present invention relates to the field of cardiac medicine and more particularly to diagnosing and treating diseased hearts based on the interaction between cardiac electro-physiological and cardiac bio-mechanical activity.

BACKGROUND OF THE INVENTION

Cardiovascular diseases accounted for approximately 43 percent of the mortality in the United States of America in 1991 (923,000 persons). However, many of these deaths are not directly caused by an acute myocardial infraction (AMI). Rather, many patients suffer a general decline in their cardiac output known as heart failure. Once the overt signs of heart failure appear, half the patients die within five years. It is estimated that between two and three million Americans suffer from heart failure and an estimated 200,000 new cases appear every year. In many cases heart failure is caused by damage accumulated in the patient's heart, such as damage caused by disease, chronic and acute ischemia and especially (.about.75%) as a result of hypertension.

A short discussion of the operation of a healthy heart is useful in order to appreciate the complexity of the functioning of the heart and the multitude of pathologies which can cause heart failure. FIG. 1A is a schematic drawing of a cross-section of a healthy heart 20. In general heart 20 comprises two independent pumps. One pump comprises a right atrium 22 and a right ventricle 24 which pump venous blood from an inferior and a superior vena cava to a pair of lungs (not shown) to be oxygenated. Another pump comprises a left atrium 26 and a left ventricle 28, which pump blood from pulmonary veins (not shown) to a plurality of body systems, including heart 20 itself. The two ventricles are separated by a ventricular septum 30 and the two atria are separated by an atrial septum 32.

Heart 20 has a four phase operational cycle in which the two pumps are activated synchronously. FIG. 1B shows a first phase, called systole. During this phase, right ventricle 24 contracts and ejects blood through a pulmonic valve 34 to the lungs. At the same time, left ventricle 28 contracts and ejects blood through an aortic valve 36 and into an aorta 38. Right atrium 22 and left atrium 26 are relaxed at this point and they begin filling with blood, however, this preliminary filling is limited by distortion of the atria which is caused by the contraction of the ventricles.

FIG. 1C shows a second phase, called rapid filling phase and indicates the start of a diastole. During this phase, right ventricle 24 relaxes and fills with blood flowing from right atrium 22 through a tricuspid valve 40, which is open during this phase. Pulmonic valve 34 is closed, so that no blood leaves right ventricle 24 during this phase. Left ventricle 28 also relaxes and is filled with blood flowing from left atrium 26 through a mitral valve 42, which is open. Aortic valve 36 is also closed to prevent blood from leaving left ventricle 26 during this phase. The filling of the two ventricles during this phase is affected by an existing venous pressure. Right atrium 22 and left atrium 26 also begin filling during this phase. However, due to relaxation of the ventricles, their pressure is lower than the pressure in the atria, so tricuspid valve 40 and mitral valve 42 stay open and blood flows from the atria into the ventricles.

FIG. 1D shows a third phase called diastatis, which indicates the middle of the diastole. During this phase, the ventricles fill very slowly. The slowdown in filling rate is due to the equalization of pressure between the venous pressure and the intra-cardiac pressure. In addition, the pressure gradient between the atria and the ventricles is also reduced.

FIG. 1E shows a fourth phase called atrial systole which indicates the end of the diastole and the start of the systole of the atria. During this phase, the atria contract and inject blood into the ventricles. Although there are no valves guarding the veins entering the atria, there are some mechanisms to prevent backflow during atrial systole. In left atrium 26, sleeves of atrial muscle extend for one or two centimeters along the pulmonary veins and tend to exert a sphincter-like effect on the veins. In right atrium 22, a crescentic valve forms a rudimentary valve called the eustachian valve which covers the inferior vena cava. In addition, there may be muscular bands which surround the vena cava veins at their entrance to right atria 22.

FIG. 1F is a graph showing the volume of left ventricle 24 as a function of the cardiac cycle. FIG. 1F clearly shows the additional volume of blood injected into the ventricles by the atria during atrial systole as well as the variance of the heart volume during a normal cardiac cycle. FIG. 1G is a graph which shows the time derivative of FIG. 1F, i.e., the left ventricle fill rate as a function of cardiac cycle. In FIG. 1G two peak fill rates are shown, one in the beginning of diastole and the other during atrial systole.

An important timing consideration in the cardiac cycle is that the atrial systole must complete before the ventricular systole begins. If there is an overlap between the atrial and ventricular systoles, the atria will have to force blood into the ventricle against a raising pressure, which reduces the volume of injected blood. In some pathological and induced cases, described below, the atrial systole is not synchronized to the ventricular systole, with the effect of a lower than optimal cardiac output.

It should be noted that even though the left and the right sides of heart 20 operate in synchronization with each other, their phases do not overlap. In general, right atrial systole starts slightly before left atrial systole and left ventricular systole starts slightly before right ventricular systole. Moreover, the injection of blood from left ventricle 26 into aorta 38 usually begins slightly after the start of injection of blood from right ventricle 24 towards the lungs and ends slightly before end of injection of blood from right ventricle 24. This is caused by pressures differences between the pulmonary and body circulatory systems.

When heart 20 contracts (during systole), the ventricle does not contract in a linear fashion, such as shortening of one dimension or in a radial fashion. Rather, the change in the shape of the ventricle is progressive along its length and involves a twisting effect which tends to squeeze out more blood. It should be appreciated that blood which remains in one place without moving, even in the heart, can clot, so it is very important to eject as much blood as possible out of the heart. FIG. 2 shows an arrangement of a plurality of muscle fibers 44 around left ventricle 28 which enables this type of contraction. When muscle fibers 44 are arranged in a spiral manner as shown in FIG. 2 and the activation of muscle fibers 44 is started from an apex 46 of left ventricle 28, left ventricle 28 is progressively reduced in volume from the bottom up. The spiral arrangement of muscle fibers 44 is important because muscle fibers typically contract no more than 50% in length. A spiral arrangement results in a greater change of left ventricular volume than is possible with, for example, a flat arrangement in which the fibers are arranged in bands around the heart. An additional benefit of the spiral arrangement is a leverage effect. In a flat arrangement, a contraction of 10% of a muscle fiber translates into a reduction of 10% of the ventricular radius. In a spiral arrangement with, for example, a spiral angle 48 of 45.degree., a 10% contraction translates into a 7.07% contraction in ventricular radius and a 7.07% reduction in ventricular length. Since the ventricular radius is typically smaller than the ventricular length, the net result is that, depending on spiral angle 48, a tradeoff is effected between a given amount of contraction and the amount of force exerted by that contraction.

Spiral angle 48 is not constant, rather, spiral angle 48 changes with the distance of a muscle fiber from the outer wall of the ventricle. The amount of force produced by a muscle fiber is a function of its contraction, thus, each layer is optimized to produce an optimal amount of force. Since the contraction of each muscle fiber is synchronous with the increase in the ventricular pressure (caused by the muscle contraction), it might be expected that the muscle fibers produce a maximum force at maximum contraction. However, physiological constraints on muscle fibers denote that maximal force is generated before maximal contraction. In addition, the force exerted by a muscle fiber begins to fall soon after maximum force is exerted. The varying spiral angle is a mechanism which makes it possible to increase the contractile force on the ventricle after maximum force is reached by a particular muscle fiber.

As described above, activation of the heart muscle is from the apex up. Thus, the muscle on the top of the ventricle could theoretically exert more force than the muscle at apex 46, which would cause a distention at apex 46. The varying spiral angle is one mechanism to avoid distention. Another mechanism is that the muscle near apex 46, which is activated first, is slightly more developed than the muscle at the top of the ventricle, which is activated last. As a result of the above described mechanisms, the force exerted by the ventricular wall is more evenly distributed over time and space.

As can be appreciated, a complicated mechanism is required to synchronize the activation of muscle fibers 44 so that an efficient four phase cycle is achieved. This synchronization mechanism is provided by an electrical conduction system within the heart which conducts an electrical activation signal from a (natural) cardiac pacemaker to muscle fibers 44.

FIG. 3 shows the main conduction pathways in heart 20. An SA node 50, located in right atrium 22, generates an activation signal for initiating contraction of muscle fibers 44. The activation signal is transmitted along a conduction pathway 54 to left atria 26 where the activation signal is locally disseminated via Bachman bundles and Crista terminals. The activation signal for contracting the left and right ventricles is conducted from SA node 50 to an AV node 52, where the activation signal is delayed. The ventricles are normally electrically insulated from the atria by non-conducting fibrous tissue, so the activation signal must travel through special conduction pathways. A left ventricle activation signal travels along a left pathway 58 to activate left ventricle 28 and a right ventricle activation signal travels along a right pathway 56 to activate right ventricle 24. The activation signal is locally disseminated in the left and right ventricles via Purkinje fibers 60. Generally, the conduction pathways convey the activation signal to apex 46 where they are locally disseminated via Purkinje fibers 60 and propagation over the rest of the heart is achieved by conduction in muscle fibers 44. In general, the activation of the heart is from the inner surface towards the outer surface. It should be noted that electrical conduction in muscle fibers 44 is generally faster along the direction of the muscle fibers. Thus, the conduction velocity of the activation signals in heart 20 is generally anisotropic.

As can be appreciated, the delay in AV node 52 results, in a healthy heart, in proper ventricular systolic sequencing. The temporal distribution of the activation signal in the ventricular muscle results in the activation of the ventricles from the apex up. In a healthy heart the activation signal propagates across left ventricle 28 in approximately 60 milliseconds. In an externally paced heart, where the activation signal is not conducted through Purkinje fibers 60 or in a diseased heart, the propagation time is typically longer, such as 150 milliseconds. Thus, disease and external pacing affect the activation profile of the heart.

Cardiac muscle cells usually exhibit a binary reaction to an activation signal; either the cell responds normally to the activation signal or it does not respond at all. FIG. 4 is a graph showing changes in the voltage of a single cardiac muscle cell in reaction to the activation signal. The reaction is generally divided into five stages. A rapid depolarization stage 62 occurs when the muscle cell receives an activation signal. During this stage, which lasts a few milliseconds, the potential of the cell becomes rapidly positive. After depolarization, the muscle fiber rapidly repolarizes during a rapid repolarization stage 64 until the cell voltage is approximately zero. During a slow repolarization stage 66, also known as the plateau, the muscle cell contracts. The duration of stage 66, the plateau duration, is directly related to the amount of work performed by the muscle cell. A relatively fast repolarization stage 68 follows, where the muscle cell repolarizes to its original potential. Stage 66 is also known as the refractory period, during which the cell cannot be activated by another activation signal. During stage 68, the cell is in a relative refractory period, during which the cell can be activated by an exceptionally strong activation signal. A steady state 70 follows in which the muscle cell is ready for another activation.

It should be appreciated that the contraction of cardiac muscle cells is delayed in time from their activation. In addition the duration of the contraction is generally equal to the duration of the plateau.

An important factor which may affect the length of the plateau is the existence of ionic currents which propagate from the most recently activated portions of the heart towards the earlier activated portions of the heart. As can be appreciated, the ionic current starts at the last activated portion of the heart and progresses back along the path of the activation. Thus, it is the later activated portions of the heart which are first affected by the ionic current. As a result, the repolarization of these cells is relatively faster than the repolarization of the first activated muscle fibers, and their contraction time is relatively shorter. As can be appreciated, in a healthy heart, where the propagation time of the activation signal is relatively short, the ionic currents are significantly smaller than in a diseased or externally paced heart.

One of the main results of the contraction of the ventricles is increased intra-ventricular pressure. In general, when the intra-cardiac pressure is higher, the outflow from the heart into the circulatory system is stronger and the efficiency of the heart is higher. A mathematical relationship termed Laplace's law can be used to model the relationship between the pressure in the ventricle and the tension in the wall of the ventricle. Laplace's law was formulated for generally spherical or cylindrical chambers with a distentible wall, however, the law can be applied to the ventricles since they are generally elongated spherical in shape. FIGS. 5A-C show three formulations for determining the tension in a portion of the ventricle wall, all of which are based of the law of Laplace. In FIG. 5A, the tension across a cross-section of the wall is shown wherein T, the tension in the wall, is equal to the product of P, the transmural pressure across the wall, r (squared), the radius of the ventricle, and .pi.. FIGS. 5B and C show formulas for calculating the tension per unit in portions of the ventricular wall, for example in FIG. 5C, for a unit cross-sectional area of muscle in a wall of thickness .delta..

As can be appreciated, if r, the radius of the ventricle, is large, a higher tension is needed to produce the same pressure change as in a ventricle with a smaller radius. This is one of the reasons that ventricular dilation usually leads to heart failure. The heart muscle is required to produce a higher tension is order to achieve the same pressure gradient. However, the heart is not capable of producing the required tension, so, the pressure gradient, and thus the cardiac efficiency, are reduced.

Unfortunately, not all people have healthy hearts and vascular systems. Some types of heart problems are caused by disease. HCM (hypertrophic cardiomyopathy) is a disease in which the left ventricle and, in particular, the ventricular septum hypertrophy, sometimes to an extent which blocks the aortic exit from the left ventricle. Other diseases, such as atrophy causing diseases reduce the amount of muscle fibers in portions of the heart.

A very common cause of damage to the heart is ischemia of the heart muscle. This condition, especially when manifesting itself as an acute myocardial infraction (heart attack), can create dead zones in the heart which do not contain active muscle. An additional, and possibly more important effect, is the non-conducting nature of these dead zones which may upset the natural activation sequence of the heart. In some cases, damaged heart tissue continues to conduct the activation signal, albeit at a variable or lower velocity, which may cause arrhythmias.

A chronic ischemic condition is usually caused by blockage of the coronary arteries, usually by arteriosclerosis, which limits the amount of oxygen which can reach portions of the heart muscle. When more work (i.e., more tension) is required of the heart muscle and an increase in oxygen supply is not available, the result is acute pain, and if the supply is cut off for an extended period, death of the starved muscle will follow.

When the output of the heart is insufficient, a common result is hypertrophy of the heart, usually of the left ventricle. Hypertrophy is a compensatory mechanism of the heart for increasing the output volume. However, in a chronic condition, hypertrophy has generally negative effects. For example, arrhythmias, congestive heart failure (CHF) and permanent changes in the morphology of the heart muscle (ventricular modeling) may result from hypertrophy.

One of the most common cardio-vascular diseases is hypertension. A main effect of hypertension is increased cardiac output demand, which causes hypertrophy since the blood must be pumped against a higher pressure. Furthermore, hypertension usually aggravates other existing cardiac problems.

The human heart has many compensatory and adaptive mechanisms, termed cardiac reserve, so that not all cardiac pathologies manifest as heart disease. Once the cardiac reserve is used up, the heart cannot keep up with the demand and heart failure may result. One measure of heart function and efficiency is the left ventricle ejection factor, which is the ratio between the amount of blood in the left ventricle during diastole and the amount of blood exiting during systole. It should be noted that a significant portion of the change in ventricular volume between systole and diastole is due to the thickening of activated muscle fibers. Another measure of heart function is the left ventricle stroke volume, which is the amount of blood which is ejected from the left ventricle each heart beat. It should be noted that once the cardiac reserve is used up it is difficult, if not impossible, for the heart to increase its output when needed, such as during exercise.

There are many ways in which non-optimal timing of the activation of the heart can result in lower cardiac output. In AF (atrial fibrillation) one or both atria does not contract in correct sequence with its associated ventricle. As a first result, the atria does not inject blood into its associated ventricle during atrial systole, so the ventricle volume is not maximized before ventricular systole, and stroke volume is slightly reduced. If the right atria is fibrillating, sequencing of the AV node is non-regular, which results in the ventricles contracting at an irregular rate, and the heart output is further reduced.

In some cases of a conduction block between the SA node and the ventricles, such as caused by a damaged AV node, the contraction of the atria is not synchronized to the contraction of the ventricles, which also results in a lower heart output.

Another type of timing deficiency results when there are large dead areas in the heart muscle which do not conduct electrical signals. The activation signal must circumvent the dead areas, which results in a longer pathway (and longer delay time) for the activation signal reaching some portions of the heart. In some cases, these portions of the heart are activated long after the rest of the heart has already contracted, which results in a reduced contribution of these portions to the total cardiac output.

Heart muscle which is stressed before it is activated, heart muscle which is weakened (such as by ischemia) and portions of the heart which have turned into scar tissue, may form aneurysms. As can be appreciated from Laplace's law, portions of the ventricle wall which do not generate enough tension to offset the tension induced by the intra-cardiac pressure must increase their local radius in response to the pressure overload. The stretched wall portion thins out and may burst, resulting in the death of the patient. The apex of the left ventricle is especially susceptible to aneurysms since it may be very thin. In addition, the total pressure in the ventricle and the flow from the ventricle are reduced as the aneurysm grows, so the heart output is also reduced. Although weak muscle should be expected to hypertrophy in response to the greater need, in some cases, such as after an AMI, hypertrophy may not occur before irreversible tissue changes are caused by the stretching.

Perfusion of the heart muscle usually occurs during diastole. However, if the diastole is very long, such as when the activation signal is propagated slowly, some portions of the heart may not be oxygenated properly, resulting in functional ischemia.

As mentioned above, one of the adaptation mechanisms of the heart is hypertrophy, in which the size of the heart increases to answer increased demand. However, hypertrophy increases the danger of arrhythmias, which in some cases reduce heart output and in others, such as VF (ventricular fibrillation) are life threatening. Arrhythmias are also caused by damaged heart tissues which generate erroneous activation signals and by blocks in the conduction system of the heart.

In some cases arrhythmias of the heart are treated using medicines, in others, by implanting a pacemaker or a defibrillator. A common pacemaker implanting procedure, for example for treating the effects of AF, includes:

(a) ablating or removing the AV node; and

(b) implanting a pacing electrode in the apex of the heart. The location of the pacing electrode may be changed (during the procedure) if the heart does not beat at a desired sequence for a given output of the pacemaker.

It is also known to pace using multiple electrodes, where the activation signal is initiated from a selected one or more of the electrodes, depending on sensed electrical values, such as sequence, activation time and depolarization state. Typically, the pacing regime is adapted to a specific arrhythmia. Sometimes, logic is included in the pacemaker which enables it to identify and respond to several types of arrhythmia.

U.S. Pat. No. 5,403,356 to Hill et al. describes a method of preventing atrial arrhythmias by adapting the pacing in the right atrium in response to a sensed atrial depolarization, which may indicate an arrhythmia.

Sometimes the pacing is performed for more than one chamber. For example, in dual chamber pacing, both left and right ventricles are separately paced. There have been attempts to use dual chamber pacing to relive aortic obstruction caused by HCM. The aortic exit from the left ventricle is located between the left and right ventricle, so that when both ventricles contract simultaneously, the aorta is squeezed from all sides. In a healthy heart, the ventricular septum does not obstruct the aorta, however, in an HCM-diseased heart, the enlarged septum obstructs the aortic exit from the left ventricle. When pacing to reduce aortic obstruction, the contractions of the left and right ventricles are stepped, so that when the left ventricle contracts, the right ventricle dilates and the aorta is less compressed.

Lameh Fananapazir, et al., in "Long-Term Results Of Dual-Chamber (DDD) Pacing In Obstructive Hypertrophic Cardiomyopathy", Circulation, Vol. 90, No. 60, pp 2731-2742, December 1994, describes the effects of pacing a HCM-diseased heart using DDD pacing at the apex of the right ventricle. One effect is that the muscle mass near the pacing location is reduced, i.e., the ventricular septum is atrophied. The atrophy is hypothesized to be caused by the changes in workload at the paced location which are due to the late activation time of ventricular segments far from the pacing location.

Margarete Hochleitner, et al., in "Long-Term Efficiency Of Physiologic Dual-Chamber Pacing In The Treatment Of End-Stage Idiopathic Dilated Cardiomyopathy", American Journal of Cardialogy, volume 70, pp 1320-1325, 1992, describes the effect of DDD pacing on hearts which are dilated as a result of idiopathic dilated cardiomyopathy. DDD pacing resulted in an improvement of cardiac function and in a reduction in hypertrophy in several patients. In addition, it is suggested that positioning the ventricular electrode of the DDD pacemaker in near the apex of the right ventricle reduced the stress at the apex of the left ventricle, by its early activation.

Xavier Jeanrenaud, et al., in "Effects Of Dual Chamber Pacing In Hypertrophic Obstructive Cardiomypathy", The Lancet, Vol. 339, pp 1318-1322, May 30, 1992, teaches that to ensure success of DDD pacing in HCM diseased hearts, an optimum AV interval (between atrial activation and ventricular activation) is required.

Several methods may be used to treat heart failure. One method is to connect assist pumps to the patient's circulatory system, which assist the heart by circulating the blood. To date, no satisfactory long-term assist pump has been developed. In some cases, a diseased heart is removed and replaced by another human heart. However, this is an expensive, complicated and dangerous operation and not many donor hearts are available. Artificial hearts suffer from the same limitations as assist pumps and, like them, are not yet practical.

Certain types of heart failure, such as those caused by conduction blocks in the AV node or by AF can be helped by the implantation of a pacemaker, as described above.

Some cases of heart failure can be helped by medicines which either strengthen the heart, correct arrhythmias or reduce the total volume of blood in the body (which reduces blood pressure). However, many cases of heart failure can only be treated by reducing the activity of the patient. Ultimately, once the cardiac reserve is used up, most cases of heart failure cannot be treated and result in death.

U.S. Pat. No. 5,391,199, the disclosure of which is incorporated herein by reference, discloses apparatus and method for mapping the electrical activity of the heart.

SUMMARY OF THE INVENTION

It is an object of some aspects of the present invention to provide methods of augmenting the compensatory mechanisms of the heart.

Another object of some aspects of the present invention is to provide methods of mapping the local physiological values and/or the shape of the heart to determine the activation profile of the heart and, preferably, to analyze the resulting maps to determine possible optimizations in the activation profile.

Yet another object of some aspects of the present invention is to control the adaptation mechanisms in the heart so that the heart output or some other parameter of the heart is optimized. Alternatively or additionally, the adaptation mechanisms of the heart are utilized to effect change in the morphology of the heart, such as by redistributing muscle mass.

Still another object of some aspects of the present invention is to control the activation sequence of the heart so that the heart output or some other physiological variable of the heart is optimized, preferably, in real-time.

When used herein, the terms "physiological variable" and "cardiac parameter" do not include electrical activity, rate, arrhythmia or sequencing of the heart. The term "local physiological value" does not include electrical activity, per se, rather it refers to a local physiological state, such as contraction of local heart muscle, perfusion or thickness. The term "location" refers to a location on or in an object, such as the heart muscle. For example, a valve or an apex of the heart. "Position" refers to a position in space, usually relative to a known portion of the heart, for example, 1.5 inches perpendicular from the apex of the heart.

An object of some aspects of the present invention is related to pacemakers which are adapted to control the adaptation mechanisms of the heart and/or to optimize heart parameters.

In a preferred embodiment of the invention, the mechanical motion of the heart muscle is mapped using a catheter having a position sensor near its distal end. The mapping includes:

(a) placing the catheter into contact with the heart wall;

(b) determining the position of the distal end of the cathe