Evaluation of vagus nerve stimulation using heart rate variability analysis

1. An implantable vagus nerve stimulation (VNS) system, comprising:

a sensor configured to measure ECG data for a patient;

a stimulation subsystem comprising a pulse generator and at least one stimulating nerve electrode configured to deliver VNS therapy to the patient, wherein the VNS therapy is delivered according to a duty cycle comprising an ON period during which a VNS dose is applied and an OFF period during which the VNS dose is suspended; and

a control system comprising a processor configured to perform a real-time heart rate variability analysis with the ECG data by:

measuring R-R intervals between successive R-waves for the ECG data measured during at least a portion of the ON period and at least a portion of the OFF period during the VNS therapy, wherein the at least a portion of the ON period is a stimulation period of the VNS therapy and the at least a portion of the OFF period is a baseline period of the VNS therapy;

generating a plot in real-time of each R-R interval against an immediately successive R-R interval for each of the stimulation period and the baseline period configured to be displayed on a display;

determining, based on the plot, a centroid of each of the stimulation period plot and the baseline period plot; and

determining a distance between the centroids of the stimulation period plot and the baseline period plot,

wherein the plotted R-R intervals measured during the stimulation period are represented differently than the plotted R-R intervals measured during the baseline period.

2. The implantable VNS system of claim 1 , wherein the real-time heart rate variability analysis is a Poincaré analysis.

3. The implantable VNS system of claim 1 , wherein the control system is further configured to perform the real-time heart rate variability analysis by determining, based on the plot,

a standard deviation from an axis of a line perpendicular to an identity line for each of the stimulation period plot and the baseline period plot.

4. The implantable VNS system of claim 1 , wherein the control system is further configured to:

compare the distance to a threshold value.

5. The implantable VNS system of claim 4 , wherein the control system is further configured to, in response to the distance being less than the threshold value, perform at least one of:

sending an alert to a physician of the patient; or

modifying an intensity of the VNS dose applied to the patient.

6. The implantable VNS system of claim 1 , wherein the control system is further configured to control the stimulation subsystem to increase the VNS dose delivered to the patient according to a titration schedule.

7. The implantable VNS system of claim 6 , wherein the control system is configured to perform the real-time heart rate variability analysis in response to an increase in the VNS dose.

8. The implantable VNS system of claim 1 , wherein the control system is configured to prepare periodic reports for a physician of the patient based on the real-time heart rate variability analysis.

9. A vagus nerve stimulation (VNS) system, comprising:

an external programmer comprising a processor; and

an implantable system comprising:

a sensor configured to measure ECG data for a patient and transmit the ECG data to the external programmer; and

a stimulation subsystem comprising a pulse generator and at least one stimulating nerve electrode configured to deliver VNS therapy to the patient, wherein the VNS therapy is delivered according to a duty cycle comprising an ON period during which a VNS dose is applied and an OFF period during which the VNS dose is suspended;

wherein the processor of the external programmer is configured to:

receive the ECG data from the implantable system; and

perform a real-time heart rate variability analysis with the ECG data by:

measuring R-R intervals between successive R-waves for the ECG data measured during at least a portion of the ON period and at least a portion of the OFF period during the VNS therapy, wherein the at least a portion of the ON period is a stimulation period of the VNS therapy and the at least a portion of the OFF period is a baseline period of the VNS therapy;

generating a plot in real-time of each R-R interval against an immediately successive R-R interval for each of the stimulation period and the baseline period configured to be displayed on a display;

determining, based on the plot, a centroid of each of the stimulation period plot and the baseline period plot; and

determining a distance between the centroids of the stimulation period plot and the baseline period plot,

wherein the plotted R-R intervals measured during the stimulation period are represented differently than the plotted R-R intervals measured during the baseline period.

10. The VNS system of claim 9 , wherein the real-time heart rate variability analysis is a Poincaré analysis.

11. The VNS system of claim 9 , wherein the external programmer is further configured to perform the real-time heart rate variability analysis by determining, based on the plot,

a standard deviation from an axis of a line perpendicular to an identity line for each of the stimulation period plot and the baseline period plot.

12. The VNS system of claim 9 , wherein performing wherein the external programmer is further configured to:

compare the distance to a threshold value.

13. The VNS system of claim 12 , wherein the external programmer is further configured to, in response to the distance being less than the threshold value:

display an alert; or

transmit a command to the implantable system to increase an intensity of the VNS dose applied to the patient.

14. The VNS system of claim 9 , wherein the external programmer is further configured to display the stimulation period plot and the baseline period plot on a display.

15. A vagus nerve stimulation (VNS) system, comprising:

a local telemetry device comprising a processor; and

an implantable system, comprising:

a sensor configured to measure ECG data for a patient and transmit the ECG data to the local telemetry device; and

a stimulation subsystem comprising a pulse generator and at least one stimulating nerve electrode configured to deliver VNS therapy to the patient, wherein the VNS therapy is delivered according to a duty cycle comprising an ON period during which a VNS dose is applied and an OFF period during which the VNS dose is suspended;

wherein the processor of the local telemetry device is configured to:

receive the ECG data from the implantable system; and

perform a real-time heart rate variability analysis with the ECG data by:

measuring R-R intervals between successive R-waves for the ECG data measured during at least a portion of the ON period and at least a portion of the OFF period during the VNS therapy, wherein the at least a portion of the ON period is a stimulation period of the VNS therapy and the at least a portion of the OFF period is a baseline period of the VNS therapy; and

generating a plot in real-time of each R-R interval against an immediately preceding R-R interval for each of the stimulation period and the baseline period configured to be displayed on a display;

determining, based on the plot, a centroid of each of the stimulation period plot and the baseline period plot;

determining a distance between the centroids of the stimulation period plot and the baseline period plot,

wherein the plotted R-R intervals measured during the stimulation period are represented differently than the plotted R-R intervals measured during the baseline period.

16. The VNS system of claim 15 , wherein the real-time heart rate variability analysis is a Poincaré analysis.

17. The VNS system of claim 15 , wherein the local telemetry device is further configured to perform the real-time heart rate variability analysis by determining, based on the plot

a standard deviation from an axis of a line perpendicular to an identity line for each of the stimulation period plot and the baseline period plot.

18. The VNS system of claim 15 , wherein the local telemetry device is configured to prepare periodic reports for a physician of the patient based on the real-time heart rate variability analysis.