U.S. patent application number 15/414561 was filed with the patent office on 2017-07-27 for treatment of congestive heart failure with electrical stimulation, and associated systems and methods.
The applicant listed for this patent is Nevro Corp.. Invention is credited to Kerry Bradley, James R. Thacker.
Application Number | 20170209699 15/414561 |
Document ID | / |
Family ID | 59360991 |
Filed Date | 2017-07-27 |
United States Patent
Application |
20170209699 |
Kind Code |
A1 |
Thacker; James R. ; et
al. |
July 27, 2017 |
TREATMENT OF CONGESTIVE HEART FAILURE WITH ELECTRICAL STIMULATION,
AND ASSOCIATED SYSTEMS AND METHODS
Abstract
Systems and methods for treating congestive heart failure with
high frequency stimulation are disclosed. A representative method
for treating a patient includes applying an electrical signal
having a frequency of from about 1 kHz to about 100 kHz to the
patient via a treatment system that includes a signal delivery
element in electrical communication with the patient's vagus nerve
at a portion of the vagus nerve located at or proximate to the
anterior interventricular junction of the patient's heart. The
method can further include automatically detecting at least one
physiological parameter of the patient, automatically determining
at least one of an ejection fraction of the patient's heart and a
correlate of the ejection fraction based on the detected parameter,
and automatically adjusting the applied signal based on the
determined ejection fraction.
Inventors: |
Thacker; James R.; (Homer,
AK) ; Bradley; Kerry; (Glendale, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Nevro Corp. |
Redwood City |
CA |
US |
|
|
Family ID: |
59360991 |
Appl. No.: |
15/414561 |
Filed: |
January 24, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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62286892 |
Jan 25, 2016 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/36171 20130101;
A61N 1/056 20130101; A61N 1/3627 20130101; A61N 1/36114 20130101;
A61N 1/36139 20130101 |
International
Class: |
A61N 1/362 20060101
A61N001/362; A61N 1/36 20060101 A61N001/36; A61N 1/05 20060101
A61N001/05 |
Claims
1. A method for treating congestive heart failure in a patient,
comprising: applying an electrical signal to the patient via a
treatment system that includes a signal delivery element in
electrical communication with the patient's vagus nerve at a
portion of the vagus nerve located at or proximate to the anterior
interventricular junction of the patient's heart, the electrical
signal having a frequency in a range of from about 1 kHz to about
100 kHz; automatically detecting at least one physiological
parameter of the patient; based on the detected parameter,
automatically determining an ejection fraction indicator that is at
least one of an ejection fraction of the patient's heart and a
correlate of the ejection fraction; and automatically adjusting the
applied signal based on the determined ejection fraction
indicator.
2. The method of claim 1 wherein automatically adjusting the
applied signal includes stopping the application of the applied
signal in response to detecting an ejection fraction indicator
greater than or equal to a target ejection fraction threshold.
3. The method of claim 2 wherein applying the electrical signal
occurs at a first time, and wherein automatically adjusting the
applied signal includes applying the electrical signal at a second
time in response to detecting an ejection fraction indicator less
than the target ejection fraction threshold.
4. The method of claim 1 wherein automatically adjusting the
applied signal includes increasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction indicator less than a
target ejection fraction threshold.
5. The method of claim 1 wherein automatically adjusting the
applied signal includes decreasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction indicator greater than
or equal to a target ejection fraction threshold.
6. The method of claim 1 wherein: automatically detecting a
physiological parameter includes automatically detecting the
patient's heart rate; and automatically adjusting the applied
signal includes increasing at least one of an amplitude of the
applied signal and a pulse width of the applied signal in response
to the increase in the patient's heart rate.
7. The method of claim 1 wherein applying the electrical signal
includes applying the signal to the patient via a lead positioned
at or proximate to the atrial-ventricular fat pads of the patient's
heart.
8. The method of claim 1 wherein applying the electrical signal
includes applying the signal with a pulse width less than or equal
to 1/(2.times.the frequency of the signal).
9. The method of claim 1 wherein the treatment system includes an
implantable treatment system.
10. The method of claim 1 wherein the at least one detected
physiological parameter includes at least one of the patient's
heart rate, the patient's blood pressure, and the patient's blood
flow rate.
11. A method for treating congestive heart failure in a patient,
comprising: applying an electrical signal to an epicardial fat pad
of the patient's heart, the applied signal having a frequency of
from about 1 kHz to about 100 kHz; automatically monitoring an
ejection fraction of the patient; automatically comparing the
monitored ejection fraction value to a predetermined threshold; and
based on the comparison, automatically adjusting the applied
signal.
12. The method of claim 11 wherein automatically adjusting the
applied signal includes stopping the application of the applied
signal in response to detecting an ejection fraction greater than
or equal to a target ejection fraction threshold.
13. The method of claim 12 wherein applying the electrical signal
occurs at a first time, and wherein automatically adjusting the
applied signal includes applying the electrical signal at a second
time in response to detecting an ejection fraction less than the
target ejection fraction threshold.
14. The method of claim 11 wherein automatically adjusting the
applied signal includes increasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction less than a target
ejection fraction threshold.
15. The method of claim 11 wherein automatically adjusting the
applied signal includes decreasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction greater than or equal to
a target ejection fraction threshold.
16. A system for treating congestive heart failure in a patient,
comprising: an electrical signal generator having a computer
readable storage medium; an implantable signal delivery element
coupled to the signal generator, wherein the signal delivery
element is configured to be positioned proximate an epicardial fat
pad of the patient and apply an electrical signal having a
frequency in a range of from about 1 kHz to about 100 kHz to neural
tissue proximate and/or within the epicardial fat pad; and wherein
the computer-readable storage medium has instructions that when
executed: determine in real-time at least one of an ejection
fraction of the patient's heart and a correlate of the ejection
fraction; and adjust the signal applied by the signal delivery
element in response to the determined ejection fraction.
17. The system of claim 16, further comprising a sensor in
communication with the computer-readable storage medium, wherein
the sensor is configured to detect a physiological parameter of the
patient, and wherein the instructions, when executed, calculate the
ejection fraction based on the physiological parameter.
18. The system of claim 16 wherein the signal generator is an
implantable signal generator.
19. The system of claim 16 wherein the instructions, when executed,
and in response to a determined ejection fraction greater than or
equal to a predetermined target threshold, cease to apply the
electrical signal.
20. The system of claim 16 wherein the instructions, when executed,
and in response to a determined ejection fraction less than or
equal to a predetermined target threshold, start application of the
electrical signal.
21. The system of claim 16 wherein the instructions, when executed,
and in response to a determined ejection fraction less than or
equal to a predetermined target threshold, increase at least one of
an amplitude or a pulse width of the electrical signal.
22. The system of claim 16 wherein the signal delivery element is
configured to be positioned within a coronary blood vessel of the
patient.
23. A method for treating congestive heart failure in a patient,
comprising: applying an electrical signal to the patient via a
treatment system that includes a signal delivery element positioned
at an epicardial fat pad of the patient's heart, the electrical
signal having a frequency in a range of from about 1 kHz to about
100 kHz; automatically detecting at least one physiological
parameter of the patient via one or more sensing elements; based on
the detected parameter, automatically determining an ejection
fraction indicator that is at least one of an ejection fraction of
the patient's heart and a correlate of the ejection fraction; and
automatically adjusting the applied signal based on the determined
ejection fraction indicator.
24. The method of claim 23 wherein automatically adjusting the
applied signal includes stopping the application of the applied
signal in response to detecting an ejection fraction indicator
greater than or equal to a target ejection fraction threshold.
25. The method of claim 23 wherein applying the electrical signal
occurs at a first time, and wherein automatically adjusting the
applied signal includes applying the electrical signal at a second
time in response to detecting an ejection fraction indicator less
than the target ejection fraction threshold.
26. The method of claim 23 wherein automatically adjusting the
applied signal includes increasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction indicator less than a
target ejection fraction threshold.
27. The method of claim 23 wherein automatically adjusting the
applied signal includes decreasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction indicator greater than
or equal to a target ejection fraction threshold.
28. The method of claim 23 wherein: automatically detecting a
physiological parameter includes automatically detecting the
patient's heart rate; and automatically adjusting the applied
signal includes increasing at least one of an amplitude of the
applied signal and a pulse width of the applied signal in response
to the increase in the patient's heart rate.
29. The method of claim 23 wherein applying the electrical signal
includes applying the signal to the patient via a lead positioned
at or proximate to the atrial-ventricular fat pads of the patient's
heart.
30. The method of claim 23 wherein applying the electrical signal
includes applying the signal with a pulse width less than or equal
to 1/(2.times.the frequency of the signal).
31. The method of claim 23 wherein the treatment system includes an
implantable treatment system.
32. The method of claim 23 wherein the at least one detected
physiological parameter includes at least one of the patient's
heart rate, the patient's blood pressure, and the patient's blood
flow rate.
33. A system for treating congestive heart failure in a patient,
comprising: an implantable electrical signal generator having a
computer readable storage medium; an implantable signal delivery
element coupled to the signal generator, wherein the signal
delivery element is configured to be positioned at or proximate the
patient's vagus nerve at a portion of the vagus nerve located at or
proximate to the interventricular junction of the patient's heart,
and wherein the signal delivery element is configured to apply an
electrical signal having a frequency in a range of from about 1 kHz
to about 100 kHz to neural tissue proximate the portion of the
vagus nerve; and wherein the computer-readable storage medium has
instructions that when executed: determine an ejection fraction
indicator that is at least one of an ejection fraction of the
patient's heart and a correlate of the ejection fraction; and
adjust the signal applied by the signal delivery element in
response to the determined ejection fraction indicator.
34. The system of claim 33, further comprising a sensor in
communication with the computer-readable storage medium, wherein
the sensor is configured to detect a physiological parameter of the
patient, and wherein the instructions, when executed, calculate the
ejection fraction indicator based on the physiological
parameter.
35. The system of claim 33 wherein the instructions, when executed,
and in response to a determined ejection fraction indicator greater
than or equal to a predetermined target threshold, cease to apply
the electrical signal.
36. The system of claim 33 wherein the instructions, when executed,
and in response to a determined ejection fraction indicator less
than or equal to a predetermined target threshold, start
application of the electrical signal.
37. The system of claim 33 wherein the instructions, when executed,
and in response to a determined ejection fraction indicator less
than or equal to a predetermined target threshold, increase at
least one of an amplitude or a pulse width of the electrical
signal.
38. The system of claim 33 wherein the signal delivery element is
configured to be positioned within a coronary blood vessel of the
patient.
39. A system for treating congestive heart failure in a patient,
comprising: an implantable electrical signal generator having a
computer readable storage medium; an implantable signal delivery
element coupled to the signal generator, wherein the signal
delivery element is configured to be positioned at least partially
within the coronary sinus of the patient's heart, and wherein the
signal delivery element is configured to apply an electrical signal
having a frequency in a range of from about 1 kHz to about 100 kHz
to neural tissue proximate the coronary sinus; and wherein the
computer-readable storage medium has instructions that when
executed: determine an ejection fraction indicator that is at least
one of an ejection fraction of the patient's heart and a correlate
of the ejection fraction; and adjust the signal applied by the
signal delivery element in response to the determined ejection
fraction indicator.
40. The system of claim 39, further comprising a sensor in
communication with the computer-readable storage medium, wherein
the sensor is configured to detect a physiological parameter of the
patient, and wherein the instructions, when executed, calculate the
ejection fraction indicator based on the physiological
parameter.
41. The system of claim 39 wherein the instructions, when executed,
and in response to a determined ejection fraction indicator greater
than or equal to a predetermined target threshold, cease to apply
the electrical signal.
42. The system of claim 39 wherein the instructions, when executed,
and in response to a determined ejection fraction indicator less
than or equal to a predetermined target threshold, start
application of the electrical signal.
43. The system of claim 39 wherein the instructions, when executed,
and in response to a determined ejection fraction indicator less
than or equal to a predetermined target threshold, increase at
least one of an amplitude or a pulse width of the electrical
signal.
44. A method for treating congestive heart failure in a patient,
comprising: applying an electrical signal to the patient via a
treatment system that includes a signal delivery element positioned
at least partially within the coronary sinus of the patient's
heart, the electrical signal having a frequency in a range of from
about 1 kHz to about 100 kHz; automatically detecting at least one
physiological parameter of the patient via one or more sensing
elements; based on the detected parameter, automatically
determining an ejection fraction indicator that is at least one of
an ejection fraction of the patient's heart and a correlate of the
ejection fraction; and automatically adjusting the applied signal
based on the determined ejection fraction indicator.
45. The method of claim 44 wherein automatically adjusting the
applied signal includes stopping the application of the applied
signal in response to detecting an ejection fraction indicator
greater than or equal to a target ejection fraction threshold.
46. The method of claim 45 wherein applying the electrical signal
occurs at a first time, and wherein automatically adjusting the
applied signal includes applying the electrical signal at a second
time in response to detecting an ejection fraction indicator less
than the target ejection fraction threshold.
47. The method of claim 44 wherein automatically adjusting the
applied signal includes increasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction indicator less than a
target ejection fraction threshold.
48. The method of claim 44 wherein automatically adjusting the
applied signal includes decreasing at least one of an amplitude of
the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction indicator greater than
or equal to a target ejection fraction threshold.
Description
CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application claims priority to pending U.S.
Provisional Application No. 62/286,892, filed Jan. 25, 2016, and is
incorporated herein by reference.
TECHNICAL FIELD
[0002] The present technology is directed generally to treatment of
congestive heart failure with electrical stimulation, and
associated systems and methods.
BACKGROUND
[0003] Congestive heart failure (CHF) is a chronic condition
characterized by a reduction in contraction strength (e.g.,
contractility) of one or both of the main pumping chambers of the
heart--the left and right ventricles. Reduced contractility of the
ventricles reduces the volume of blood ejected by each ventricle
per heart beat (e.g., stroke volume). When this occurs, the heart
cannot pump blood with normal efficiency, and blood and other
fluids begin to build up within the cardiovascular system and other
parts of the body, such as the lungs, liver, abdomen, and lower
extremities. In some cases of CHF, the myocardium (e.g., heart
muscle tissue) becomes so weakened that the ventricles stretch or
dilate, thereby damaging the Purkinje fibers located in the walls
of the ventricles. The Purkinje fibers are responsible for carrying
the contraction impulse to the myocardium of the ventricles, and
thus damage to the Purkinje fibers by the dilated ventricles
compromises the electrical conduction system of the heart and
reduces the synchronization of contractility, further compromising
the ejection fraction. Accordingly, there is a need for systems and
methods for treating congestive heart failure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0004] FIGS. 1A and 1B are anterior and posterior views,
respectively, of a human heart.
[0005] FIG. 2A is a partially schematic illustration of an
implantable treatment system positioned to deliver electrical
signals to the heart in accordance with several embodiments of the
present technology.
[0006] FIG. 2B is a partially schematic illustration of a portion
of an implantable treatment system positioned to deliver electrical
signals to the heart in accordance with several embodiments of the
present technology.
[0007] FIG. 3 is a flow diagram illustrating a method for treating
congestive heart failure in accordance with an embodiment of the
present technology.
[0008] FIG. 4 is a flow diagram illustrating a method for
determining a representative (e.g., maximum) treatment amplitude in
accordance with an embodiment of the present technology.
[0009] FIG. 5 is a flow diagram illustrating a method for adjusting
a treatment signal in response to real-time ejection fraction
feedback in accordance with an embodiment of the present
technology.
DETAILED DESCRIPTION
[0010] The present technology is directed generally to systems for
treating congestive heart failure (CHF), and in particular, to
systems for treating CHF by improving contraction strength of the
left and/or right ventricles via electrical stimulation. In one
embodiment, the present technology includes a treatment system
having an implantable signal generator and a signal delivery
element configured to apply an electrical signal to a
parasympathetic nerve innervating a portion of a patient's heart.
The system includes one or more real-time feedback mechanisms for
evaluating the efficacy of the applied signal and automatically
adjusting the applied signal based on the efficacy. For example, in
some embodiments the treatment system can automatically determine
an ejection fraction of the patient's heart and adjust one or more
parameters of the applied electrical signal based on the ejection
fraction.
[0011] Definitions of selected terms are provided under heading 1.0
("Definitions"). General aspects of the anatomical and
physiological environment in which the disclosed technology
operates are described below under heading 2.0 ("Introduction")
with reference to FIGS. 1A and 1B. An overview of the treatment
systems in which the disclosed technology operates is described
below under heading 3.0 ("Overview") with reference to FIGS. 2A and
2B. Particular embodiments of the technology are described further
under heading 4.0 ("Representative Embodiments") with reference to
FIGS. 3-5. Additional embodiments are described under heading 5.0
("Additional Embodiments).
1.0 Definitions
[0012] As used herein, "vagus nerve" refers to any of the
following: portions of the left vagus nerve, the right vagus nerve,
and/or the cervical vagus nerve, branches of the vagus nerve such
as the superior cardiac nerve, superior cardiac branch, and
inferior cardiac branch, and the vagus trunk. Similarly,
stimulation of the vagus nerve is described herein by way of
illustration and not limitation, and it is to be understood that in
some embodiments of the present technology, other autonomic and/or
parasympathetic nerves and/or parasympathetic tissue are
stimulated, including sites where the vagus nerve innervates a
target organ, vagal ganglia, nerves in the epicardial fat pads, a
carotid artery, a jugular vein (e.g., an internal jugular vein), a
carotid sinus, a coronary sinus, a vena cava vein, a pulmonary
vein, and/or a right ventricle, for treatment of heart conditions
or other conditions.
[0013] As used herein, "high frequency" or "HF" refers to a
frequency of from about 1 kHz to about 100 kHz, or from about 1.2
kHz to about 100 kHz, or from about 1.5 kHz to about 100 kHz, or
from about 2 kHz to about 50 kHz, or from about 3 kHz to about 20
kHz, or from about 3 kHz to about 15 kHz, or from about 5 kHz to
about 15 kHz, or from about 3 kHz to about 10 kHz, or 1 kHz, 2 kHz,
3 kHz, 4 kHz, 5 kHz, 8 kHz, 9 kHz, 10 kHz, 11 kHz, 12 kHz, 15 kHz,
20 kHz, 50 kHz, or 100 kHz. As used herein, the term "about" refers
to values within +/-10% of the stated value. Moreover, as used
herein, "low frequency" or "LF" refers to a frequency less than
about 1 kHz.
[0014] As used herein, "real-time" refers to within 10 seconds or
less, within 5 seconds or less, within 3 seconds or less, within 2
seconds or less, within 1 second or less, within 0.5 seconds or
less, within 0.25 seconds or less, and within 0.1 seconds or
less.
2.0 Introduction
[0015] FIGS. 1A and 1B are anterior and posterior views,
respectively, of a human heart H. As shown in FIGS. 1A and 1B, the
heart H comprises four chambers, the right atrium RA, the left
atrium LA, the right ventricle RV, and the left ventricle LV. The
right and left atria RA, LA are separated from the right and left
ventricles RV, LV by a groove known as the coronary or
atrioventricular sulcus AVS. The anterior interventricular sulcus
AIS and posterior interventricular sulcus PIS are grooves that
separate the right and left ventricles RV, LV. Each of the
atrioventricular sulcus AVS, the anterior interventricular sulcus
AIS, and posterior interventricular sulcus PIS are surrounded by
epicardial fat pads FP. The great cardiac vein GCV begins near the
apex A of the heart and extends in a superior direction within the
anterior interventricular sulcus AIS until eventually curving
around the left side of the heart H within the atrioventricular
sulcus AVS. A posterior portion of the great cardiac vein GCV
empties into the coronary sinus CS, which is also positioned within
the atrioventricular sulcus AVS.
3.0 Overview
[0016] FIG. 2A schematically illustrates a representative treatment
system 100 for improving contractility of a patient's heart H,
arranged relative to the general anatomy of a patient's heart H and
chest region. As shown in FIG. 2A, parasympathetic innervation of
the heart muscle is partially controlled by the vagus nerve V,
which has branches that feed into one or more plexuses N located
on, in and/or adjacent the epicardial fat pads FP. The treatment
system 100 includes a signal delivery system 101 having a signal
generator 102 (e.g., a pulse generator) and a signal delivery
device or element 104. The signal generator 102 can be connected
directly to the signal delivery element 104, or it can be coupled
to the signal delivery element 104 via a signal link 108 (e.g., an
extension). In one embodiment, signal generator 102 can be
connected to signal delivery element 104 via wireless signal
communication or wireless signal transmission. In some embodiments,
the signal generator 102 may be implanted subcutaneously within a
patient P, while in other embodiments signal generator 102 can be
external to the patient. As shown in FIG. 2A, the signal delivery
element 104 is configured to be positioned at or proximate to an
epicardial fat pad FP, and to apply an electrical signal to the
adjacent vagal plexus N. It is believed that high frequency
modulation at or proximate the epicardial fat pads FP can modulate
the parasympathetic nerve plexus(es) N located on or within the
epicardial fat pads FP, thereby improving parasympathetic tone
(e.g., the electrical activity of the parasympathetic nerve fibers)
and ventricular contraction strength. As such, in one embodiment,
the electrical signal applied to the vagal plexus N is a high
frequency electrical signal (or high frequency therapy signal).
[0017] The signal generator 102 can transmit signals (e.g.,
electrical signals or therapy signals) to the signal delivery
element 104 that up-regulate (e.g., stimulate or excite) and/or
down-regulate (e.g., block or suppress) target nerves (e.g., local
vagal nerves). As used herein, and unless otherwise noted, to
"modulate," "stimulate," or provide "modulation" or "stimulation"
to the target nerves refers generally to having either type of the
foregoing effects on the target nerves. The signal generator 102
can include a machine-readable (e.g., computer-readable) medium
containing instructions for generating and transmitting suitable
therapy signals. The signal generator 102 and/or other elements of
the treatment system 100 can include one or more processors 110,
memories 112 and/or input/output devices. Accordingly, the process
of providing electrical signals, detecting physiological parameters
of the patient, determining ejection fraction, adjusting the
modulation signal, and/or executing other associated functions can
be performed by computer-executable instructions contained by
computer-readable media located at the signal generator 102 and/or
other system components. The signal generator 102 can include
multiple portions, elements, and/or subsystems (e.g., for directing
signals in accordance with multiple signal delivery parameters)
housed in a single housing, as shown in FIG. 2A, or in multiple
housings.
[0018] The signal delivery system 101 can include one or more
sensing elements 140 for detecting one or more physiological
parameters of the patient before, during, and/or after the
application of electrical therapy signals. In some embodiments, one
or more of the sensing elements 140 can be carried by the signal
generator 102, the signal delivery element 104, and/or other
implanted components of the system 101. In other embodiments, the
sensing element(s) 140 can be an extracorporeal or implantable
device separate from the signal generator 102 and/or signal
delivery element 104. Representative sensing elements 140 include
one or more of: an electrocardiogram ("ECG") unit, an impedance
cardiography unit, a subcutaneous sensor, a ventricular sensor, an
activity sensor (e.g., an accelerometer), a ventricular
intracardiac sensor, an atrial intracardiac sensor, a temperature
sensor, a flow rate sensor, a chemical sensor, a biosensor, an
electrochemical sensor, a hemodynamic sensor, an optical sensor
and/or other suitable sensing devices. Physiological parameters
detected by the sensing element(s) 140 include heart rate, blood
pressure, blood flow rate, activity level, ECG readings, impedance
cardiography readings, ventricular and/or atrial pressure, and/or
any correlates and/or derivatives of the foregoing parameters
(e.g., raw data values, including voltages and/or other directly
measured values).
[0019] In a representative embodiment, the signal delivery system
101 is configured to operate in either a "calibration mode" or an
"active mode." In the calibration mode, the signal delivery system
101 is configured to apply a low frequency electrical signal (also
referred to herein as the "LF calibration signal") via the signal
delivery element 104 at the treatment site to determine a
representative (e.g., maximum) signal amplitude that can be applied
during subsequent treatment. In one embodiment, for example, the
maximum signal amplitude is determined during the calibration mode
to be the lower of: (1) the amplitude at which direct, immediate
changes are observed to the heart rate, myocardial activation, or
chamber sequencing, and (2) the amplitude which creates sensations
which are perceived by the patient. In a particular embodiment, the
signal delivery system 101 is also configured to apply a high
frequency electrical signal (referred to herein as the "HF
calibration signal") when in the calibration mode to validate the
maximum signal amplitude identified by the LF calibration signal.
In the active mode, the signal delivery system 101 is configured to
apply a high frequency electrical signal (also referred to herein
as the "HF treatment signal" or "HF therapy signal") at the
treatment site to modulate the parasympathetic nerves proximate the
treatment site. Parameters of the electrical signals applied by the
signal delivery system 101 during calibration mode and/or active
mode can be (1) automatically adjusted in response to a feedback
mechanism and/or in accordance with a preset program (described in
greater detail with reference to FIGS. 3-5), (2) manually adjusted
in accordance with patient and/or practitioner inputs, and/or (3)
automatically adjusted in a random or pseudorandom manner. "For
example, a physician may find it beneficial to reduce the
likelihood of the targeted nerves developing an adaptive,
neuroplastic response that could diminish the efficacious effects
of the applied signal over time. In such cases, an algorithm may be
used to alter the applied amplitude of energy delivery in a
pseudorandom manner. For example, the physician may set boundaries
for the signal amplitude, such as a lower boundary of 0 mA and an
upper boundary determined during calibration. Additionally, the
physician may specify a schedule for varying the amplitude within
the preset bounds, such as one amplitude change every N beats
during the ventricular refractory period, M changes every beat
during the ventricular refractory period, etc. Signal parameters
include, for example, frequency, amplitude, pulse width, and duty
cycle. It will be appreciated that in other embodiments, the signal
delivery system 101 can be configured to operate in more than two
modes.
[0020] In some embodiments, the signal generator 102 can obtain
power to generate the therapy signals from an external power source
114. The external power source 114 can transmit power to the
implanted signal generator 102 using electromagnetic induction
(e.g., RF signals). For example, the external power source 114 can
include an external coil 116 that communicates with a corresponding
internal coil (not shown) within the implantable signal generator
102. The external power source 114 can be portable for ease of
use.
[0021] In another embodiment, the signal generator 102 can obtain
the power to generate therapy signals from an internal power
source, in addition to or in lieu of the external power source 114.
For example, the implanted signal generator 102 can include a
non-rechargeable battery or a rechargeable battery to provide such
power. When the internal power source includes a rechargeable
battery, the external power source 114 can be used to recharge the
battery. The external power source 114 can in turn be recharged
from a suitable power source (e.g., conventional wall power).
[0022] During at least some procedures, an external programmer 120
(e.g., a trial modulator) can be coupled to the signal delivery
element 104 during an initial procedure, prior to implanting the
signal generator 102. For example, a practitioner (e.g., a
physician and/or a company representative) can use the external
programmer 120 in calibration mode to vary the signal parameters
provided to the signal delivery element 104 in real-time, and
select optimal or particularly efficacious signal parameters and/or
signal delivery element 104 placement, as discussed in greater
detail below with reference to FIG. 4. In a typical process, the
practitioner uses a cable assembly 128 to temporarily connect the
external programmer 120 to the signal delivery element 104. Whether
calibrating the signal delivery system 101 or applying the HF
treatment signal, the practitioner can test the efficacy of the
signal delivery element 104 in an initial position and/or with
initial signal parameters. The practitioner can then disconnect the
cable assembly 128 (e.g., at a connector 130), reposition the
signal delivery element 104, and reapply the electrical signal.
This process can be performed iteratively until the practitioner
confirms the desired therapy signal parameters and/or position for
the signal delivery element 104 are clinically effective.
Optionally, the practitioner can move the partially implanted
signal delivery element 104 without disconnecting the cable
assembly 128.
[0023] After a trial period with the external programmer 120, the
practitioner can implant the implantable signal generator 102
within the patient P for longer term treatment. The signal delivery
parameters provided by the signal generator 102 can still be
updated after the signal generator 102 is implanted, via a wireless
physician's programmer 124 (e.g., a physician's remote).
[0024] FIG. 2B is a partially schematic illustration of the heart H
along with a signal delivery element 104 implanted within the great
cardiac vein GCV. The parasympathetic nerve fibers N depicted in
FIG. 2A are not shown in FIG. 2B for purposes of clarity. In the
representative embodiment, the signal delivery element 104
comprises a flexible, isodiametric lead or lead body that carries
features or elements for delivering an electrical signal to the
treatment site after implantation. As used herein, the terms "lead"
and "lead body" include any of a number of suitable substrates
and/or support members that carry devices for providing therapy
signals to the patient. For example, the lead body can include one
or more electrodes or electrical contacts 105 that direct
electrical signals into the patient's tissue, such as to improve
parasympathetic tone (e.g., parasympathetic electrical activity).
In other embodiments, the signal delivery element 104 can include
devices other than a lead body (e.g., a paddle) and/or other lead
configurations (e.g., cardiac pacing leads, implantable
cardioverter defibrillator (ICD) leads, cardiac resynchronization
therapy (CRT) leads, left heart leads, epicardial leads, etc.) that
also direct electrical signals and/or other types of signals to the
patient. In a particular embodiment, the signal delivery system 101
(FIG. 2A) includes more than one signal delivery element 104 (e.g.,
two signal delivery elements 104, three signal delivery elements
104, four signal delivery elements 104, etc.), each configured to
apply electrical signals at different locations and/or coordinate
signal delivery to deliver a combined signal to the same (or
generally the same) anatomical location.
[0025] As shown in FIG. 2B, the signal delivery element 104 can be
positioned along at least a portion of the great cardiac vein GCV
at or proximate the anterior interventricular sulcus AIS. In other
embodiments, the signal delivery element 104 can be positioned at
other cardiac locations at or proximate the epicardial fat pads FP.
As used herein, "at or proximate the epicardial fat pads" refers to
a position of the signal delivery element 104 that is in, on or
otherwise in direct contact with a coronary vessel that is in
direct contact with the targeted epicardial fat pad FP, and/or in
direct contact with the adipocyte tissue of the targeted fat pad
FP. For example, the signal delivery element 104 can be directly
coupled to the fat pad FP tissue, positioned within a coronary
artery, positioned within a coronary vein not in direct contact
with the targeted epicardial fat pad FP and/or in direct contact
with the adipocyte tissue of the targeted fat pad FP (e.g., the
middle cardiac vein, the small cardiac vein, one or more anterior
cardiac veins, the coronary sinus, etc.), positioned at an exterior
portion of a coronary artery and/or coronary vein, positioned along
at least a portion of the great cardiac vein GCV apart from the
anterior interventricular sulcus AIS (e.g., at or proximate the
atrioventricular sulcus AVS, etc.), and/or other suitable
locations. In some embodiments, the signal delivery element 104 can
be positioned on or within a coronary blood vessel such that the
signal delivery element 104 spans more than one portion of the host
blood vessel. For example, the signal delivery element 104 can be
positioned such that (a) a first portion of the signal delivery
element 104 coincides with at least a portion of the great cardiac
vein GCV at or proximate the anterior interventricular sulcus AIS,
and (b) a second portion of the signal delivery element 104
coincides with at least a portion of the great cardiac vein GCV at
or proximate the atrioventricular sulcus AVS. In particular
embodiments, the signal delivery element 104 can be coupled to
and/or apply an electrical signal to more than one type of tissue
(e.g., the adipose tissue of the fat pads FP and the neural tissue
of the parasympathetic plexus N (FIG. 2A), the connective tissue of
the blood vessel(s) and the neural tissue of the parasympathetic
plexus N, etc.).
4.0 Representative Embodiments
[0026] FIGS. 3-5 illustrate a representative method for treating
CHF and/or improving cardiac contractility utilizing the treatment
system 100 described above with reference to FIGS. 2A and 2B. FIG.
3 illustrates an overall process 300 in accordance with a
particular embodiment of the disclosure. The overall process 300
includes determining a representative (e.g., maximum) treatment
amplitude (process portion 310), applying an HF treatment signal to
a patient via the signal delivery system 101 (FIG. 2A) (process
portion 312), and automatically detecting one or more physiological
parameters of the patient (process portion 314). The process 300
can further include automatically determining an ejection fraction
of the patient's heart based on the detected physiological
parameter (process portion 316) and, based on the determined
ejection fraction, automatically adjusting one or more parameters
of the HF treatment signal (process portion 318). FIGS. 4 and 5
describe further aspects of particular embodiments of the foregoing
process.
[0027] FIG. 4 is a block diagram 400 illustrating a representative
method for determining a representative (e.g., maximum) signal
amplitude prior to modulating the nerves to prevent unwanted
effects on the electrical conduction system of the heart (e.g.,
tachycardia, bradycardia, etc.) during treatment. In block 410,
with the signal delivery system 101 (FIG. 2A) in calibration mode,
the practitioner applies the calibration signal to the treatment
site. In the embodiment shown, an LF calibration signal is applied.
In an alternative embodiment, however, a HF calibration signal may
be applied. In a particular embodiment, the LF calibration signal
can have a frequency of from about 0.1 to about 2.5 Hz, and in some
embodiments, less than 1 Hz. In some embodiments the LF calibration
signal can have a pulse width greater than 600 microseconds, and in
certain embodiments, of from about 100 microseconds to about 2.5
milliseconds. During application of the LF calibration signal, the
practitioner and/or system processor 110 can monitor an ECG of the
patient for any changes (e.g., timing changes in the PQRST wave)
while increasing the amplitude of the applied signal from a
starting amplitude value (e.g., starting at an amplitude of 0.1 mA
and increasing the amplitude in increments; for example of 0.1 mA,
0.2 mA, 0.5 mA, or 1.0 mA). As indicated by blocks 412 and 414, as
long as no cardiac effect is detected on the ECG, the practitioner
and/or processor 110 (FIG. 2A) can continue to increase the
amplitude of the LF calibration signal. As indicated by blocks 412
and 416, if at any point the practitioner and/or system processor
110 detects a change in the ECG, the amplitude of applied signal
can cease to increase and the amplitude at which the change in the
ECG was detected is automatically stored in system memory 112 (FIG.
2A) (e.g., within the signal generator 102 (FIG. 2A) and/or the
external programmer 120 (FIG. 2A)) and/or manually entered by the
practitioner.
[0028] In a particular embodiment, the signal delivery system 101
(FIG. 2A) is optionally configured to determine a representative
(e.g., maximum) HF signal amplitude by applying an HF calibration
signal to the treatment site and monitoring the patient's ECG while
increasing the HF calibration signal's amplitude from a starting
amplitude value. In some embodiments, the HF calibration signal has
a pulse width less than or equal to 1/(2*(the frequency of the HF
calibration signal), and in a particular embodiment, of from about
100 nanoseconds to less than or equal to 1/(2*(the frequency of the
HF calibration signal). In other embodiments, the signal can have
other suitable pulse widths. Similar to the LF calibration process
400, as long as no cardiac effect is detected on the ECG, the
practitioner and/or processor 110 (FIG. 2A) continues to increase
the amplitude of the HF calibration signal. If at any point the
practitioner and/or system processor 110 detects a change in the
ECG, the amplitude of applied HF calibration signal can cease to
increase and the amplitude at which the change in the ECG was
detected is automatically stored in system memory 112 (FIG. 2A)
(e.g., within the signal generator 102 (FIG. 2A) and/or the
external programmer 120 (FIG. 2A)) and/or manually input by the
practitioner. Although it is expected that the electrical energy
required to trigger cardiac activity at the LF calibration signal
will be much lower than the electrical energy required at the HF
calibration signal, it can be advantageous in some procedures to
determine the maximum treatment amplitude with the HF calibration
signal to validate the maximum treatment signal amplitude
determined using the LF calibration signal. Moreover, in some
instances the physician may use the HF calibration signal to set
the upper and lower bounds of the HF treatment signal amplitude.
For example, in some embodiments the upper bound of the HF
treatment signal amplitude can be set to the representative LF
calibration signal amplitude plus 0.5*(the representative HF
calibration signal amplitude minus the representative LF
calibration signal amplitude). In yet other embodiments, the
physician may set the HF treatment signal amplitude upper bound to
0.9*(the LF calibration signal amplitude).
[0029] Once the maximum treatment signal amplitude has been
determined, the system 101 (FIG. 2A) can be put in active mode (as
indicated in FIG. 3). In active mode, the signal delivery system
101 is configured to apply a therapy signal to the treatment site.
Without being bound by theory, HF signals are believed to have
significantly improved therapeutic effects when compared to LF
signals in modulating the vagal nerve at the heart because it is
believed that the LF signal parameters required for an LF signal to
therapeutically modulate the vagal nerve would also necessarily
activate the myocardium and induce unwanted cardiac effects (e.g.,
tachycardia, bradycardia, etc.). In some embodiments, an HF
treatment signal is applied and can have a starting amplitude of
about 90% of the maximum signal amplitude (determined during
calibration mode). In a representative embodiment, the HF treatment
signal is a pulse train with a duty-cycle from about 1% on to about
90% on (e.g., 10% or about 10% on, 25% or about 25% on, 50% or
about 50% on, 70% or about 70% on, etc.). The HF treatment signal
can have a pulse width of from about 1 .mu.s to about 80 .mu.s, and
in some embodiments, of from about 20 .mu.s to about 60 .mu.s
(e.g., 30 .mu.s, 37 .mu.s, 42 .mu.s, etc.). The HF treatment signal
can also have an interpulse width of from about 0 .mu.s to about 50
.mu.s, or of from about 10 .mu.s to about 40 .mu.s. In other
embodiments, the HF treatment signal can be any charge-balanced,
alternating-current waveform, such as a bi-phasic waveform, a sine
waveform, a square waveform, a triangular waveform, a rectangular
waveform, etc. In yet other embodiments, the treatment signal is
not pulsed and instead is delivered continuously. In such
embodiments, charge balancing can be achieved via active recharge
on a pulse-by-pulse basis. As discussed in greater detail below
with reference to FIG. 5, the signal delivery system 101 can
control the timing of the application of the HF treatment signal
based on one or more feedback mechanisms and/or preset programs
(e.g., based on time of day). For example, the system 101 can be
programmed to deliver the HF treatment signal for seconds, minutes,
hours, days, weeks, and/or months at a time. In these and other
embodiments, the signal delivery system 101 can be configured to
apply the HF treatment signal continuously while implanted.
[0030] Application of the HF treatment signal at the treatment site
(e.g., at or proximate an epicardial fat pad) is expected to
modulate one or more vagal nerves at or proximate to the treatment
site, thereby improving parasympathetic tone and cardiac
contractility. One way to assess contractility and/or the efficacy
of the treatment is by measuring ejection fraction, or the
percentage of blood pumped out of the heart during each beat. An
increase in ejection fraction indicates improved contractility and,
likewise, a decrease in ejection fraction indicates reduced
contractility. Under resting conditions, healthy adults have an
average ejection fraction between 50% and 75%. Below 50%, the
patient may experience a variety of symptoms, including shortness
of breath, inability to exercise, swelling of the feet and lower
legs, fatigue, weakness, and rapid or irregular heartbeat. Below
30%, the patient's quality of life is minimal and death may be
imminent.
[0031] When the signal delivery system 101 (FIG. 2A) is in active
mode--whether applying the treatment signal or not--the treatment
system 100 and/or signal delivery system 101 can be configured to
continuously or intermittently monitor one or more physiological
parameters of the patient via the one or more sensing elements 140
(FIG. 2A). In a representative embodiment, the sensing element(s)
140 are positioned and/or otherwise configured to sense one or more
physiological parameters that, when analyzed together by the
processor 110, provide a reliable, real-time estimate of ejection
fraction that can be used to adjust the treatment signal. Such
physiological parameters include systolic pressure, diastolic
pressure, interatrial pressure, flow rate, arterial pressure, heart
rate, ventricular volume, ventricular impedance, blood oxygen
saturation, and/or any derivative of the foregoing. In a particular
embodiment, for example, the system 101 includes an algorithm that
continuously and/or iteratively monitors ventricular impedance and
heart rate and, based on those parameters, determines a change in
ventricular volume over time (dVV/dt). In another embodiment, the
system 101 includes one or more transducers configured for
echocardiographic signaling. For example, in some embodiments the
signal delivery element 104 (FIG. 2A) includes an array of
piezoelectric transducers configured to emit sound waves towards
one or more chambers of the heart, detect the reflected sound
waves, and convert the reflected sound waves into a signal for
storage and/or processing by the processor 110 (FIG. 2A). In these
and other embodiments, the system 101 can include one or more
transducers separate from the signal delivery element 104 and
configured to be positioned at or near the heart and/or other
internal and/or external anatomical locations. It will be
appreciated that the system 101 can include multiple algorithms for
determining and/or estimating ejection fraction. For example, in a
particular embodiment, the system 101 can include an algorithm that
estimates ejection fraction by monitoring changes in contraction
velocity (e.g., via an accelerometer at the lead).
[0032] FIG. 5 is a block diagram 500 illustrating a method for
adjusting the timing and/or one or more other parameters of the
treatment signal in response to real-time ejection fraction
feedback. As indicated at blocks 510 and 512, when the signal
delivery system 101 is in active mode, the sensing element(s) 140
(FIG. 2A) continuously or intermittently communicate the sensed
parameter values to the system processor 110 (FIG. 2A) and/or
memory 112 (FIG. 2A). The processor 110 can determine an ejection
fraction measurement (also referred to herein as the "EF
measurement") based on the sensed parameters (block 512). The EF
measurement can be an instantaneous ejection fraction value or set
of values, an average ejection fraction value over a period of
time, and/or any derivative or correlate of either of the
foregoing, such as a change in ejection fraction over time (dEF/dt)
(or lack thereof) and a rate of change of ejection fraction EF over
time (d.sup.2EF/dt.sup.2) (or lack thereof).
[0033] In block 514, the processor 110 (FIG. 2A) compares the EF
measurement with a target ejection fraction threshold (also
referred to herein as "target EF threshold"). The target EF
threshold is a standardized or patient-specific ejection fraction
metric that represents an improvement in ejection fraction relative
to the patient's ejection fraction prior to treatment. The target
EF threshold can be a single value or range of values, and can be
determined prior to treatment and/or adjusted during treatment.
Similar to the EF measurement, the target EF threshold can be an
instantaneous ejection fraction value or set of values, an average
ejection fraction value over a period of time, and/or any
derivative of either of the foregoing, such as a change in ejection
fraction over time (dEF/dt) (or lack thereof) and a rate of change
of ejection fraction over time (d.sup.2EF/dt.sup.2) (or lack
thereof). Moreover, on some embodiments the system 101 (FIG. 2A)
may take into account multiple different EF measurements and/or
multiple different target EF thresholds at decision block 514,
and/or require more than one comparison before choosing a course of
action.
[0034] As indicated by block 530, if the EF measurement is less
than the target EF threshold, the processor 110 (FIG. 2A) will take
one of two actions based on whether the signal delivery system 101
(FIG. 2A) is currently applying a treatment signal. If the EF
measurement is less than the target EF threshold and the signal
delivery system 101 is presently applying the treatment signal, one
or more parameters of the treatment signal may not be sufficient to
modulate the parasympathetic nerves. In such a scenario (indicated
by block 544), the processor 110 can adjust one or more signal
parameters (e.g., increase the treatment signal amplitude and/or
the pulse width of the treatment signal) to increase the intensity
of the treatment signal. As indicated by blocks 540 and 542, the
processor 110 will not increase the treatment signal magnitude if
the maximum treatment signal amplitude has already been reached.
Alternatively, if the EF measurement is less than the target EF
threshold and the signal delivery system 101 is not presently
applying the treatment signal, then the processor 110 can initiate
application of the treatment signal.
[0035] As indicated by block 520, if the EF measurement is greater
than or equal to the target EF threshold, the processor 110 (FIG.
2A) will take one of two actions based on whether the signal
delivery system 101 (FIG. 2A) is currently applying a treatment
signal. If the EF measurement is greater than the target EF
threshold and the signal delivery system 101 is presently applying
the treatment signal, it may be beneficial to cease applying the
treatment signal (indicated by block 526) but continue monitoring
ejection fraction should the EF measurement fall below the target
EF threshold. Alternatively, if the EF measurement is greater than
the target EF threshold and the signal delivery system 101 is not
presently applying the treatment signal, then the processor 110 can
continue to not apply the treatment signal (indicated by block 524)
but monitor ejection fraction should the EF measurement fall below
the target EF threshold.
[0036] It will be appreciated that in any of the above embodiments,
the signal delivery system 101 (FIG. 2A) can measure other
parameters (in addition to ejection fraction) and can additionally
or alternatively adjust the timing and/or signal parameters of the
treatment signal in response to such other measurements and/or any
parameter sensed by the sensing elements 140. For example, the
signal delivery system 101 can be configured to detect an average
heart rate outside of a target heart rate threshold, and, for
example, if the detected heart rate is greater than the target
heart rate threshold while the treatment signal is being applied,
the processor 110 can decrease the pulse width and/or increase the
amplitude of the treatment signal in order to increase the
parasympathetic tone.
5.0 Additional Embodiments
[0037] Embodiments of the presently disclosed technology are
described in the following examples. A method for treating
congestive heart failure in a patient in accordance with one
example includes applying an electrical signal to the patient via a
treatment system that includes a signal delivery element in
electrical communication with the patient's vagus nerve at a
portion of the vagus nerve located at or proximate to the anterior
interventricular junction of the patient's heart, with the
electrical signal having a frequency of from about 1 kHz to about
100 kHz. The method further includes automatically detecting at
least one physiological parameter of the patient, automatically
determining at least one of an ejection fraction of the patient's
heart and a correlate of the ejection fraction based on the
detected parameter, and automatically adjusting the applied signal
based on the determined ejection fraction. In some embodiments of
the method, automatically adjusting the applied signal includes
stopping the application of the applied signal in response to
detecting an ejection fraction greater than or equal to a target
ejection fraction threshold. In these and other embodiments,
automatically adjusting the applied signal includes increasing at
least one of an amplitude of the applied signal and a pulse width
of the applied signal in response to detecting an ejection fraction
less than a target ejection fraction threshold and/or automatically
adjusting the applied signal includes decreasing at least one of an
amplitude of the applied signal and a pulse width of the applied
signal in response to detecting an ejection fraction greater than
or equal to a target ejection fraction threshold. In some
embodiments, automatically detecting a physiological parameter
includes automatically detecting the patient's heart rate, and
automatically adjusting the applied signal includes increasing at
least one of an amplitude of the applied signal and a pulse width
of the applied signal in response to the increase in the patient's
heart rate. Further, in at least some embodiments of the method,
applying the electrical signal occurs at a first time and
automatically adjusting the applied signal includes applying the
electrical signal at a second time in response to detecting an
ejection fraction less than the target ejection fraction threshold.
In a particular embodiment, applying the electrical signal includes
applying the signal to the patient via a lead positioned at or
proximate to the atrial-ventricular fat pads of the patient's
heart. In certain embodiments of the method, applying the
electrical signal includes applying the signal with a pulse width
less than or equal to 1/(2.times.the frequency of the signal). In
further embodiments, the treatment system includes an implantable
treatment system. In yet further embodiments, the at least one
detected physiological parameter includes at least one of the
patient's heart rate, the patient's blood pressure, and the
patient's blood flow rate.
[0038] A method for treating congestive heart failure in a patient
in accordance with another representative example includes applying
an electrical signal having a frequency of from about 1 kHz to
about 100 kHz to an epicardial fat pad of the patient's heart,
automatically monitoring an ejection fraction of the patient,
automatically comparing the monitored ejection fraction value to a
predetermined threshold, and based on the comparison, automatically
adjusting the applied signal. In some embodiments of the method,
automatically adjusting the applied signal includes stopping the
application of the applied signal in response to detecting an
ejection fraction greater than or equal to a target ejection
fraction threshold. In these and other embodiments, automatically
adjusting the applied signal includes increasing at least one of an
amplitude of the applied signal and a pulse width of the applied
signal in response to detecting an ejection fraction less than a
target ejection fraction threshold and/or automatically adjusting
the applied signal includes decreasing at least one of an amplitude
of the applied signal and a pulse width of the applied signal in
response to detecting an ejection fraction greater than or equal to
a target ejection fraction threshold. In a particular embodiment of
the method, applying the electrical signal occurs at a first time,
and wherein automatically adjusting the applied signal includes
applying the electrical signal at a second time in response to
detecting an ejection fraction less than the target ejection
fraction threshold.
[0039] Still a further representative example of a system for
treating congestive heart failure in a patient in accordance with
the present technology includes an electrical signal generator
having a computer readable storage medium, and an implantable
signal delivery element coupled to the signal generator. The signal
generator can be configured to be positioned proximate an
epicardial fat pad of the patient and apply an electrical signal
having a frequency of from about 1 kHz to about 100 kHz to neural
tissue proximate and/or within the epicardial fat pad. In some
embodiments of the system, the computer-readable storage medium has
instructions that, when executed, determine an ejection fraction of
the patient's heart in real-time and adjust the signal applied by
the signal delivery element in response to the determined ejection
fraction. In a particular embodiment, the system further comprises
a sensor in communication with the computer-readable storage
medium. In at least some of such embodiments, the sensor is
configured to detect a physiological parameter of the patient, and
the instructions, when executed, calculate the ejection fraction
based on the physiological parameter. In a certain embodiment of
the system, the signal generator is an implantable signal
generator. In further embodiments of the system, the instructions,
when executed, and in response to a determined ejection fraction
greater than or equal to a predetermined target threshold, cease to
apply the electrical signal. In these and other embodiments, the
instructions, when executed, and in response to a determined
ejection fraction less than or equal to a predetermined target
threshold, start application of the electrical signal and/or in
response to a determined ejection fraction less than or equal to a
predetermined target threshold, increase at least one of an
amplitude or a pulse width of the electrical signal. In a
representative embodiment of the system, the signal delivery
element is configured to be positioned within a coronary blood
vessel of the patient.
[0040] From the foregoing, it will be appreciated that specific
embodiments of the disclosed technology have been described herein
for purposes of illustration, but that various modifications may be
made without deviating from the technology. For example, in some
embodiments the system 101 (FIG. 2A) can be configured to deliver
pacing signals to the heart. In such embodiments, for example, the
system 101 can include a single signal generator configured to
transmit pacing signals and modulating signals, or the system 101
can include a modulating signal generator (e.g., signal generator
102 (FIG. 2A) and a separate pacing signal generator (e.g.,
external or implantable). In those embodiments having a single
signal generator configured to transmit pacing and modulating
signals, the system 101 can include one or more signal delivery
element(s) configured to deliver pacing signals, modulating
signals, or both.
[0041] Certain aspects of the technology described in the context
of particular embodiments may be combined or eliminated in other
embodiments. For example, in some embodiments the signal generator
102 (FIG. 2A) is configured to only transmit LF or HF signals in
calibration mode, and in other embodiments the signal generator 102
may not include a calibration mode. Further, while advantages
associated with certain embodiments of the disclosed technology
have been described in the context of those embodiments, other
embodiments may also exhibit such advantages, and not all
embodiments need necessarily exhibit such advantages to fall within
the scope of the technology. Accordingly, the disclosure and
associated technology can encompass other embodiments not expressly
shown or described herein.
[0042] To the extent any materials incorporated herein by reference
conflict with the present disclosure, the present disclosure
controls.
* * * * *