SYSTEM AND METHOD FOR MEASURING EFFECTIVENESS OF AUTONOMIC NEUROSTIMULATION

Abstract

A system for evaluating an efficacy of vagus nerve stimulation is provided, wherein the system has a neurostimulator that is configured to perform vagus nerve stimulation, and a measuring component for evaluating the efficacy based on at least one parameter that is indicative of a myocardial contractile state of the heart. A corresponding method is also provided.

Claims

1. A system for evaluating an efficacy of vagus nerve stimulation, the system comprising: a neurostimulator configured to perform vagus nerve stimulation; and a measuring component for evaluating the efficacy based on at least one parameter that is indicative of a myocardial contractile state of the heart.

2. The system of claim 1, wherein the parameter is: intracardiac impedance; ventricular wall motion; heart sounds; low frequency fluid motion acoustic signals; or a parameter derived therefrom, wherein the measuring component is configured to measure the parameter.

3. The system according to claim 2, wherein the intracardiac impedance is measured in a unipolar manner, and wherein the measuring component comprises an electrode having a tip that is configured to be arranged at a location in the heart, the location of the heart including an apex of the right ventricle of the heart for measuring the intracardiac impedance.

4. The system according to claim 1, wherein the neurostimulator is configured to activate parasympathetic ganglia in the heart, and wherein for activating the ganglia the neurostimulator is configured to generate electrical impulses and to apply them via at least one or a plurality of stimulation electrodes.

5. The system according to claim 1, wherein the system is configured to determine the parameter via the measuring component during diastole and/or systole of the cardiac cycle.

6. The system according to claim 1, wherein the system is configured to repeatedly determine the parameter during vagus nerve stimulation and in an absence of vagus nerve stimulation and to compare a parameter obtained during vagus nerve stimulation with a parameter obtained in the absence of vagus nerve stimulation for evaluating an efficacy, wherein the comparison is performed by evaluating the parameter with respect to: a reference value, an upper and lower limit, a statistical moment, one or more direct or derived value from the same sensor at another time in the heart cycle, a direct or derived value from another sensor or sensors, or a state of a therapy device.

7. The system according to claim 1, wherein the system further comprises an accelerometer configured to detect movements of the patient.

8. The system according to claim 2, wherein the derived parameter corresponds to: a time period representing a waveform of the intracardiac impedance or ventricular wall motion, wherein heart sounds or acoustic signals remains flat during the isovolumetric relaxation period; or a time period between a closure of the aortic valve and an opening of the Mitral valve of the heart, which time period is estimated via a first-order derivative of the measured intracardiac impedance, ventricular wall motion, heart sounds, or acoustic signals waveform.

9. A method for evaluating an efficacy of vagus nerve stimulation, the method comprising: providing a system according to claim 1; and evaluating an efficacy of vagus nerve stimulation based on at least one parameter that is indicative of a myocardial contractile state of the heart.

10. The method of claim 9, wherein the parameter includes: intracardiac impedance; ventricular wall motion; heart sounds; low frequency fluid motion acoustic signals; or a parameter derived therefrom, wherein the parameter is measured.

11. The method according to claim 10, wherein the intracardiac impedance is an unipolar intracardiac impedance that is measured using an electrode having a tip that has been arranged at the apex of the right ventricle.

12. The method according to claim 9, wherein the parameter is determined during diastole and/or systole of the cardiac cycle.

13. The method according to claim 9, wherein the parameter is repeatedly determined during vagus nerve stimulation and in an absence of vagus nerve stimulation, and wherein the parameter obtained during vagus nerve stimulation is compared to the parameter obtained in the absence of vagus nerve stimulation for evaluating the efficacy.

14. The method according to claim 9, further comprising: detecting a movement of the patient; and deriving an activity measure of the patient from the detected movements.

15. The method according to claim 10, wherein the derived parameter corresponds to: a time period representing a waveform of an intracardiac impedance, a ventricular wall motion, heart sounds, or acoustic signals that remain flat during the isovolumetric relaxation period; or a time period between a closure of the aortic valve and an opening of a Mitral valve of the heart, wherein the time period is estimated via a first-order derivative of the measured intracardiac impedance, ventricular wall motion, heart sounds, or acoustic signals waveform.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The present invention will become more fully understood from the detailed description given hereinbelow and the accompanying drawings which are given by way of illustration only, and thus, are not limitive of the present invention, and wherein:

[0038] FIG. 1 shows a system/method according to the present invention;

[0039] FIG. 2 shows a heart suffering from compromised lusitropy due to increased sympathetic tone and the effect of VNS;

[0040] FIG. 3 shows traces of a typical electrocardiogram, the corresponding intracardiac impedance and its first derivative, wherein the systole is highlighted; and

[0041] FIG. 4 shows traces of a typical electrocardiogram, the corresponding intracardiac impedance and its first derivative, wherein the diastole is highlighted.

DETAILED DESCRIPTION

[0042] FIG. 1 shows a system 1 for evaluating an efficacy of vagus nerve stimulation VNS according to the present invention. The system 1 comprises a neurostimulator 2 that is configured to perform vagus nerve stimulation, and a measuring component 3 for evaluating the efficacy based on at least one parameter Z that is indicative of a myocardial contractile state of the heart H (e.g. as shown in the details of FIG. 1). According to an embodiment of the invention, measuring component 3 comprises or is connected to an electrode, wherein the electrode is configured to perform measurements of electrical parameters of a tissue. Measuring component 3 may also comprise processing components for computation and evaluation of the measured electrical parameters, as e.g. deriving parameter Z and evaluating the efficacy based on at least one parameter Z.

[0043] In addition, the proposed system 1 may incorporate an accelerometer 4 which measures patient activity and an algorithm which generates a patient activity trend. The patient activity trend will allow for long-term efficacy evaluation via its approximation of quality of life through activity.

[0044] Particularly, the parameter Z is an intracardiac impedance Z (or a parameter derived therefrom), wherein the measuring component 3 is configured to measure the intracardiac impedance Z, particularly by means of an electrode 30 in an unipolar configuration, wherein the electrode 30 comprises a tip 30a that is particularly arranged at the apex of the right ventricle RV. Using the unipolar electrode configuration for measuring impedance Z, the electrical path conducts through myocardium and blood, wherein the myocardium exhibits electrical impedance which is higher than blood. Consequently, the measured value of impedance Z depends on the relation of myocardium to blood within the electrical measurement path. That relation of myocardium to blood is depended on the cardiac contraction state, which is explained further in the following. FIG. 1 includes two detail illustrations which show the electrode 30 with electrode tip 30a in two different contraction states of the heart. In the pre-ejection phase, the cardiac ventricles are filled with blood and the myocardium is relaxed. As a result, there is a comparatively high volume of blood B and low portion of myocardium in the vicinity of electrode tip 30a, resulting in a measured impedance Z which is low. In the ejection phase of the heart, the blood is pumped out of the ventricles and the myocardium is in a contracted state. Consequently, a comparatively high portion of myocardium and small portion of blood surrounds electrode tip 30a, resulting in a measured impedance Z which is high.

[0045] The ability of the myocardium to change from the contracted state to the relaxed state is called cardiac lusitropy. When a patient suffers from disturbed, i.e. increased sympathetic drive, cardiac lusitropy is compromised in a way which is illustrated in FIG. 2. The four images in FIG. 2 each show an intra-cardiac lead tip 30a embedded in the RV apex at the peak of contraction. The myocardium M contracts around the lead tip 30a, enveloping it in cardiac tissue which exhibits higher measurable electrical impedance than blood B. The upper half of FIG. 2 depicts schematically cardiac contraction behavior influenced by an increased sympathetic drive and how this is represented in the impedance measurements: Cardiac lusitropy is compromised in a way that the transition time for a change of the cardiac contraction state from high impedance (upper left image) to low impedance (upper right image) is prolonged, resulting in a prolonged time for the ventricle to relax and allowing passive phase diastolic pre-filling of the ventricle. In the lower half of FIG. 2, the effect of VNS therapy on a patient suffering from increased sympathetic tone is shown: Due to an increased vagal tone, the transition time from high impedance (lower left image) to low impedance (lower right image) is reduced, resulting in normalized cardiac lusitropy.

[0046] FIG. 3 shows a typical trace of an electrocardiogram of two cardiac cycles, the corresponding impedance Z measurements its first derivative dZ/dt. The highlighted area 31 marks a systolic phase of the heart. For evaluation of the impedance Z or a parameter derived therefrom according to the invention, the signals as shown can for instance be acquired with and without VNS, followed by signal analysis and comparison, for example with such signal parts acquired during diastole, as shown in highlighted area 32 of FIG. 4.

[0047] Particularly, the efficacy of VNS can be quantified in relation to how long (time period T) the continuous Impedance waveform Z remains flat during the isovolumetric relaxation period IRVT (see upper arrow in FIG. 4). If lusitropy is improving due to VNS, the amount of time spent in this flat region will shorten. An alternative indicator can be found in the first-order derivative of the intracardiac impedance dZ/dt which will reveal the closure of the aortic valve and the opening of the mitral valve. The length of time between these two changes in valve state is also reduced with effective VNS. One approach to evaluate waveform flatness is to determine amplitude variation of the waveform. For instance, a waveform can be declared as flat when the amplitude has not varied for more than a certain percentage within a predetermined time. An exemplary process for defining flatness of an impedance waveform is given in the following: The impedance signal is sampled at a certain rate. A linear model is generated for the time/impedance pairs (such as z(t)m*t+b) for t=0, 1, . . . , n). An analysis of variance is applied and the resulting parameters are tested against the hypothesis that they differ significantly from the null hypothesis of a horizontal line (that is flat). Since real physiologic signals even when sampling a flat region will likely contain some non-zero offset and variance, these statistical moments can be tested with p-value and F-statistic to see if the flat region varies significantly from an ideal horizontal line at a fixed direct current value.

[0048] Additional methods of establishing VNS efficacy in improving cardiac function include differential estimates of inotropy and lusitropy via measurements of the intracardiac impedance at systole and diastole, respectively. In cases of both heart failure with reduced ejection fraction (HFrEF, systolic HF) and preserved ejection fraction (HFpEF, diastolic HF) the differential measure of dZ/dt at these time points improves with therapy and improved cardiac function.

[0049] Particularly, according to the invention, VNS is delivered by the system 1 with a duty cycle on period of 10-30 seconds and an off period of 30 seconds to 5 minutes. Measurements of the parameter according to the invention are taken during VNS on periods and compared against VNS off periods, allowing 5-60 seconds for the VNS effect to wash out, provide a rapid efficacy estimate of VNS during normal device operation as well as the initial VNS up-titration period after implant.

[0050] It will be apparent to those skilled in the art that numerous modifications and variations of the described examples and embodiments are possible in light of the above teaching. The disclosed examples and embodiments are presented for purposes of illustration only. Other alternate embodiments may include some or all of the features disclosed herein. Therefore, it is the intent to cover all such modifications and alternate embodiments as may come within the true scope of this invention.

[0051] The invention being thus described, it will be obvious that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are to be included within the scope of the following claims.