U.S. patent application number 13/598284 was filed with the patent office on 2012-12-20 for device and method for treating disorders of the cardiovascular system or heart.
Invention is credited to Rose PROVINCE, Amir J. TEHRANI.
Application Number | 20120323293 13/598284 |
Document ID | / |
Family ID | 39676833 |
Filed Date | 2012-12-20 |
United States Patent
Application |
20120323293 |
Kind Code |
A1 |
TEHRANI; Amir J. ; et
al. |
December 20, 2012 |
DEVICE AND METHOD FOR TREATING DISORDERS OF THE CARDIOVASCULAR
SYSTEM OR HEART
Abstract
A device and method are provided to treat heart failure by
stimulating to cause diaphragm contraction.
Inventors: |
TEHRANI; Amir J.; (San
Francisco, CA) ; PROVINCE; Rose; (San Jose,
CA) |
Family ID: |
39676833 |
Appl. No.: |
13/598284 |
Filed: |
August 29, 2012 |
Related U.S. Patent Documents
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Application
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Filing Date |
Patent Number |
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12082057 |
Apr 8, 2008 |
8265759 |
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13598284 |
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12069823 |
Feb 13, 2008 |
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12082057 |
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12044932 |
Mar 8, 2008 |
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12069823 |
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11981342 |
Oct 31, 2007 |
8140164 |
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11480074 |
Jun 29, 2006 |
8160711 |
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11271315 |
Nov 10, 2005 |
8244358 |
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11480074 |
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Nov 10, 2005 |
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10966487 |
Oct 15, 2004 |
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Jun 29, 2006 |
8160711 |
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Nov 10, 2005 |
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Oct 15, 2004 |
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10966474 |
Oct 15, 2004 |
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10686891 |
Oct 15, 2003 |
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Current U.S.
Class: |
607/42 |
Current CPC
Class: |
A61N 1/3601 20130101;
A61N 1/3621 20130101; A61N 1/3627 20130101 |
Class at
Publication: |
607/42 |
International
Class: |
A61N 1/36 20060101
A61N001/36 |
Claims
1. A method of treating heart failure comprising: sensing an
initial respiration parameter during intrinsic breathing of a
subject via at least one electrode positioned internally within the
patient; synchronizing an electrical stimulation protocol with the
sensed respiration parameter via a controller in communication with
the at least one electrode; and, applying the electrical
stimulation protocol which comprises a burst or series of pulses to
tissue associated with a phrenic nerve or diaphragm tissue to
contract a diaphragm at a beginning or during an onset of each
intrinsic breathing cycle and sustaining the electrical stimulation
protocol such that the respiration rate is reduced where a loading
on a heart of the subject is reduced.
2. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises electrically stimulating
the tissue such that inspiration is augmented.
3. The method of claim 1 wherein the step of the electrical
stimulation protocol comprises pacing each intrinsic breathing
cycle such that minute ventilation is maintained or reduced.
4. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises further applying the
electrical stimulation protocol during a beginning portion of an
inspiration cycle.
5. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises further applying the
electrical stimulation protocol during an end portion of an
inspiration cycle.
6. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises applying the electrical
stimulation protocol such that tidal volume is increased during the
reduced respiration relative to intrinsic breathing.
7. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises applying the electrical
stimulation protocol such that functional residual capacity is
increased during the reduced respiration relative to intrinsic
breathing.
8. The method of claim 15 wherein the step of applying the
electrical stimulation protocol comprises applying the electrical
stimulation protocol such that an exhalation rate is slowed
relative to the intrinsic breathing.
9. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises applying the electrical
stimulation protocol during the subject's sleep cycle.
10. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises providing a low energy
stimulation.
11. The method of claim 1 wherein the step of applying the
electrical stimulation protocol comprises applying the electrical
stimulation protocol such that a resting lung volume is increased
relative to the intrinsic breathing.
12. The method of claim 1 further comprising further applying the
electrical stimulation protocol until the intrinsic breathing is
entrained.
13. A method for treating a subject with heart failure comprising:
sensing an initial respiration parameter during intrinsic breathing
of a subject via at least one electrode positioned internally
within the patient; synchronizing an electrical stimulation
protocol with the sensed respiration parameter via a processor in
communication with the at least one electrode; and, applying the
electrical stimulation protocol which comprises a burst or series
of pulses to tissue associated with a phrenic nerve or diaphragm
tissue to contract a diaphragm at a beginning or during an onset of
each intrinsic breathing cycle and sustaining the electrical
stimulation protocol such that the intrathoracic pressure is
reduced relative to a pressure during intrinsic breathing where a
loading on a heart of the subject is reduced.
14. The method of claim 12 wherein a single hemidiaphragm is
stimulated by the electrical stimulation protocol.
15. The method of claim 12 further comprising further applying the
electrical stimulation protocol until the intrinsic breathing is
entrained.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser.
No. 12/082,057 filed Apr. 8, 2008, which claims priority of U.S.
Application Ser. No. 60/925,024 filed Apr. 18, 2007, and is a
continuation in part U.S. application Ser. No. 12/069,823 filed
Feb. 13, 2008 (now abandoned), and of U.S. application Ser. No.
12/044,932 filed Dec. 21, 2007; and of U.S. application Ser. No.
11/981,342 filed Oct. 31, 2007 (now U.S. Pat. No. 8,140,164); and
of U.S. application Ser. No. 11/480,074 filed Jun. 29, 2006 (now
U.S. Pat. No. 8,160,711); and of U.S. application Ser. No.
11/271,315 filed Nov. 10, 2005 (now U.S. Pat. No. 8,244,358); and
of U.S. application Ser. No. 11/271,554 filed Nov. 10, 2005; and of
U.S. application Ser. No. 11/271,353 filed Nov. 10, 2005; and of
U.S. application Ser. No. 11/271,264 filed Nov. 10, 2005 (now U.S.
Pat. No. 7,979,128); and of U.S. application Ser. No. 10/966,487
filed Oct. 15, 2004 (now abandoned); and of U.S. application Ser.
No. 11/480,074 filed Jun. 29, 2006 (now U.S. Pat. No. 8,160,711)
which is a continuation in part of U.S. application Ser. No.
11/271,726 filed Nov. 10, 2005 (now U.S. Pat. No. 7,970,475) which
is a continuation in part of U.S. application Ser. No. 10/966,484
filed. Oct. 15, 2004 (now abandoned); U.S. application Ser. No.
10/966,474, filed Oct. 15, 2004; U.S. application Ser. No.
10/966,421 filed Oct. 15, 2004 (now U.S. Pat. No. 8,255,056); and
U.S. application Ser. No. 10/966,472 filed Oct. 15, 2004 (now U.S.
Pat. No. 8,200,336), which are continuations in part of U.S.
application Ser. No. 10/686,891 filed Oct. 15, 2003 entitled:
BREATHING DISORDER DETECTION AND THERAPY DELIVERY DEVICE AND
METHOD, all of which are incorporated completely and without
limitation herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to treating heart failure (or
dysfunction) and other cardiovascular disorders.
BACKGROUND OF THE INVENTION
[0003] Heart failure is a complex disease with many forms and
causes. In general heart failure is defined as a condition where
the cardiac output is not adequate to meet the metabolic needs of
the body, either at rest or with exercise. Heart failure may be
preceded by heart dysfunction, including, but not limited to
ventricular dysfunction.
[0004] There are two forms of heart failure, one where the hearts
ability to expel the blood is impaired (systolic heart failure),
another where there is a defect in ventricular filling (diastolic
heart failure). Each can occur in isolation or together.
[0005] Current treatments for heart failure are available to slow
the progress of the disease but do not cure the disease. Despite
all the current therapeutic options, studies show that more than
half of heart failure patients die within 5 years of their
diagnosis.
[0006] Accordingly it would be desirable to provide new and useful
treatments for heart failure or other cardiac/cardiovascular
disease.
[0007] Pacemakers have been useful where there are cardiac
bradyarrhythmias. Defibrillators are primarily used to prevent
sudden cardiac death and therefore have not improved the status of
heart failure patients nor have they improved quality of life.
Cardiac Resychronization Therapy devices (CRTs) have been useful or
in patients with significant interventricular delay or in
preventing cardiac tachyarrhythmias or sudden cardiac death
(CRT-Ds). There are many heart failure patients who may not
substantially benefit from one or more of these treatments or may
not have an improved quality of life from such treatments. For
example, CRTs have not been approved for patients with ejections
fractions greater than 35% and thus are not available for diastolic
heart failure patients who typically have ejection fractions
greater than 50%, or for systolic patients with an ejection
fraction greater than 35%. Some studies show diastolic heart
failure to account for up to 1/3 of the patients presenting with
heart failure. In addition, because the current treatments do not
carte heart failure, additional treatment that may be used in
combination with existing treatment may be beneficial to the
patients.
[0008] Many of the drugs such as calcium channel blockers, beta
blockers, ACES inhibitors, diuretics, nitrates have had varying
degrees of effect on different manifestations of heart failure.
However, not all are useful to treat all heart failure patients.
Furthermore, due to side effects some patients withdraw from
treatment. Pharmacological therapeutic approaches to diastolic
heart failure currently recommend diuretics and nitrates while the
efficacy is uncertain for all diastolic heart failure patients with
calcium channel blockers, beta blockers, ACE inhibitors. Inotropic
agents are not recommended for diastolic patients. Accordingly it
would be desirable to provide treatment for heart failure that may
be used alone or in combination with other heart failure
treatments. It would also be desirable to provide alternative or
supplementary treatment for diastolic heart failure patients.
[0009] Another cardiovascular condition that may exist with or
without heart failure is hypertension. Hypertension is believed to
worsen heart failure. It is also believed that hypertension may
lead to diastolic heart failure. Studies have shown that treatment
of hypertension reduces the incidence of heart failure, by 30% to
50%. Accordingly it would be desirable to provide a treatment for
hypertension.
[0010] In addition, a large percentage of heart failure patients
also suffer from one or more forms of sleep apnea: obstructive
sleep apnea or central sleep apnea, (each of which have significant
clinical differences), or mixed apneas. These conditions are
believed to worsen progression of heart failure. Obstructive sleep
apnea is also believed to contribute to the development of heart
failure, particularly through hypertension.
[0011] Oxygen desaturations at night, changes in intrathoracic
pressure, and arousals may adversely affect cardiac function and
eventually result in an imbalance between myocardial oxygen
delivery and consumption. In heart failure patients with sleep
apnea, there is believed to be an increased incidence of atrial
fibrillation, ventricular arrhythmias and low left ventricular
ejection fraction. Atrial fibrillation may be caused in part by
increased right heart afterload due to hypoxic vasoconstriction
which produces pulmonary hypertension. Periodic breathing such as
Cheyne-Stokes associated with CSA, create wide fluctuations in
intrathoracic pressure with a negative cardiovascular impact.
Central sleep apnea sometimes goes undiagnosed in heart failure
patients. The untreated central sleep apnea may trigger a negative
chain of events that leads to worsening of heart failure.
[0012] Obstructive sleep apnea is believed to elicit a series of
mechanical, hemodynamic, chemical, neural and inflammatory
responses with adverse consequences for the cardiovascular system
for example, as described in Sleep Apnea and heart Failure Part I:
Obstructive Sleep Apnea. Bradley, Douglas T, MD, Floras, John S. MD
D Phil, Circulation Apr. 1, 2003. Many of these effects are
believed to exacerbate conditions of heart failure. Among these
responses, increases in blood pressure as well as increases in
sympathetic activity are associated with obstructive apneas.
[0013] Accordingly it would be desirable to treat sleep apnea in
heart failure to reduce the negative effects of the apnea on the
patient's disease status.
[0014] CPAP is the most common treatment for obstructive sleep
apnea and has been proposed for central sleep apnea. CPAP requires
an external device and patient compliance. In addition, its
cardiovascular effects are currently unclear and some researchers
believe that it can exacerbate heart failure in some patients,
particularly where positive forced pressure has a negative effect
on a heart failure patient, such as, for example, in patients where
a reduced ventricular filling would significantly reduce cardiac
output. Diaphragm stimulation has been proposed to treat central
sleep apnea by stimulating when apnea has occurred. However, the
stimulation is provided after the apnea event has occurred rather
than preventing the apnea event. Hypoglossal nerve stimulation has
been proposed to treat obstructive sleep apnea by increasing
patency in the upper airway to enable respiration. But it is
believed would not provide additional benefit to heart failure
patients other than that of treating the obstructive apnea.
[0015] It would accordingly be desirable to provide a treatment for
sleep apnea that has a symbiotic therapeutic effect in treating
heart failure or other cardiac/cardiovascular disease.
[0016] It would further be desirable to provide a treatment for
heart failure patients with sleep apnea that provides a separate or
additional function of treating heart failure.
[0017] Research has shown that voluntary control of breathing can
improve cardiac disease, including hypertension and heart failure.
It is believed that the reason for this is a biofeedback that
exists between the cardiac and respiratory systems due to
baroreceptor based reflexes, and also a common central nervous
control. Biofeedback systems for breathing control have been
provided. However, they require patient compliance and diligence.
Furthermore, because they require patient compliance, the therapy
can only occur during waking hours.
SUMMARY OF THE INVENTION
[0018] In accordance with the invention, stimulation is provided to
the diaphragm or phrenic nerve to elicit a diaphragm response to
thereby provide a therapeutic effect for a heart failure or other
cardiac or cardiovascular patient.
[0019] In accordance with one aspect of the invention, stimulation
to elicit a diaphragm response is provided to increase or normalize
lung volume and in particular to increase functional residual
capacity. It is believed that stimulation to increase or to
normalize lung volume or functional residual capacity may have one
or more effects that may be therapeutic to cardiovascular or heart
failure patients. Normalizing herein may include for example,
bringing a physiological parameter into a normal or healthy region
for patients or for a particular patient, or to a level appropriate
for a condition or state of a patient.
[0020] In accordance with another aspect of the invention
stimulation is provided to control breathing to reduce respiration
rate and thereby reduce hypertension, reduce sympathetic nerve
bias, and/or provide improved blood gas levels.
[0021] In accordance with another aspect of the invention
stimulation is provided to control minute ventilation to
therapeutically effect blood gas levels.
[0022] In accordance with another aspect of the invention,
stimulation is provided to create a deep inspiration or an
increased tidal volume to thereby reduce sympathetic nerve bias,
improve blood gas levels, stimulate reflexes for example the
Hering-Bruer reflex related to activating, stretch receptors,
increase lung volume, normalize or reset breathing or provide other
beneficial therapies to improve cardiovascular function or heart
failure condition.
[0023] In accordance with another aspect of the invention
stimulation may be provided to manipulate intrathoracic pressure to
thereby produce a therapeutic effect. According to one embodiment,
stimulation is provided to reduce intrathoracic pressure to thereby
reduce preload on the heart.
[0024] In accordance with another aspect of the invention
stimulation is provided to reduce breathing disorders to thereby
improve condition of a heart failure patient.
[0025] In accordance with another aspect of the invention a
combined cardiac rhythm management device and diaphragm/phrenic
nerve stimulation device is provided to provide an enhanced
combined treatment device.
[0026] These and other aspects of the invention are set forth
herein in the abstract, specification and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0027] FIG. 1A is a chart illustrating examples of possible
beneficial effects of stimulation in accordance with an aspect of
the invention.
[0028] FIG. 1B is a pressure volume curve illustrating use of
stimulation in accordance with an aspect of the invention.
[0029] FIGS. 2A, 2B and 2C illustrate respectively, flow, tidal
volume and stimulation envelope signals corresponding to use of a
device and method in accordance with an aspect of the
invention.
[0030] FIGS. 3A, 3B, 3C and 3D illustrate respectively, EMG, flow,
tidal volume and stimulation envelope signals corresponding to use
of a device and method in accordance with an aspect or the
invention.
[0031] FIGS. 4A, 4B, and 4C illustrate respectively, flow, tidal
volume and stimulation envelope signals corresponding to use of a
device and method in accordance with an aspect of the
invention.
[0032] FIGS. 5A, 5B, and 5C illustrate respectively, flow, tidal
volume and stimulation envelope signals corresponding to use of a
device and method in accordance with an aspect of the
invention.
DETAILED DESCRIPTION
[0033] In accordance with one aspect of the invention, stimulation
to elicit a diaphragm response is provided to increase or normalize
lung volume and in particular to increase functional residual
capacity. It is believed that stimulation to increase or to
normalize, lung volume or functional residual capacity may have one
or more effects that may be therapeutic to cardiovascular or heart
flu lure patients.
[0034] In accordance with this aspect of the invention stimulation
may be provided using a device or method as described in one or
more of the related patent applications set forth herein, to
increase or normalize lung volume or functional residual capacity.
For example, a bias stimulation may be provided to increase
functional residual capacity or to bias lung volume for a period of
time. It is believed that increasing functional residual capacity
may have one or more therapeutic effects for heart failure or other
cardiovascular patients, such as, for example, reducing effort
required to breathe; improving gas exchange, improving SaO.sub.2
levels; providing a butter to reduce fluctuations in blood gas
levels and to reduce the likelihood of crossing the PCO.sub.2
apneic threshold; and reducing episodes of obstructive apnea in OSA
patients and central sleep apnea episodes. Such buffer may also
stabilize blood gases to counter fluctuations in gas levels caused
by circulatory delay that may lead to Cheyne-Stokes respiration and
Central Sleep Apnea. Other stimulation may be provided to achieve
improved SaO.sub.2 levels or gas levels, for example, as set forth
in the related patent applications which are incorporated
completely and without limitation herein by reference. Other
stimulation may be provided that may have the effect of normalizing
lung volume, including but not limited to low frequency
stimulation, low energy stimulation, or deep inspiration
stimulation. These various stimulation techniques may also be
provided or configured to have the effect of increasing SaO.sub.2
levels to reduce load on the heart.
[0035] FIG. 1A illustrates stimulation provided with a device or
method in accordance with the invention. Stimulation is provided
using a device or method for stimulating tissue to elicit a
diaphragm response 1000. Stimulation increases or normalizes lung
volume or FRC 1001. The increase or normalization or lung volume
may improve gas exchange; increase SaO2, and/or improve breathing
stability 1002. The increase or normalization of lung volume or FRC
may move a patient to a more optimal location on the volume
pressure curve 1003 as described in more detail with respect to
FIG. 1B. Providing stimulation to increase FRC may also allow
improved gas exchange during pulmonary edema where lung inflation
creates a gradient for liquid movement from alveolar space to the
extra-interstitium 1004. It is believed that moving fluids to the
interstitial space will improve ventilation because removal of
fluids from the alveolar region will permit improved gas exchange.
An increase or normalization of lung, volume or FRC may also treat
OSA or CSA in patients with OSA (obstructive sleep apnea) or CSA
(central sleep apnea) and thereby benefit the cardiovascular system
1005. For example, one or more devices and methods described in
copending patent applications set forth above may be used to treat
OSA or CSA.
[0036] FIG. 1B illustrates a pressure/volume curve 1010
illustrating, a relationship between transthoracic pressure and
lung volume. This example illustrates, among other things how
stimulation may be provided to reduce breathing effort and/or
intrathoracic pressure change for a given inspiration volume. At
lower lung volumes 1011, a greater change in pressure is required
to increase lung volume a given amount through inspiration, thus
providing a greater work of breathing and thereby increasing
metabolic requirements and load on heart as well. Similarly at
higher lung volumes 1013, greater change in pressure and effort are
required to increase lung volume through inspiration. However, in
between the lower volumes 1011 and higher volumes 1013 there is a
steeper portion of the curve 1012 where at a given lung volume,
inspiration produces an efficient increase in lung volume with less
change in pressure required to effect a given volume and therefore
less effort required by the respiratory muscles to produce a given
change in pressure. It is believed that an increase in required
effort to breathe may result in poorer breathing or less effort and
gas exchange, particularly in heart failure patients. It is also
believed that greater fluctuations in intrathoracic pressure may
contribute the conditions affecting heart failure. Thus in
accordance with one aspect of the invention, stimulation may be
provided to increase resting lung volume so that greater breathing
efficiency and gas exchange is provided. Where a patient's normal
resting lung volume or functional residual capacity is typically
low, it may be increased. Where a patient's resting lung volume is
lower than normal for a healthy individual, it may be normalized so
that it is brought to a level where efficient breathing occurs. For
example a low lung volume 1014 may be increased, to higher lung
volumes 1015 or 1016 which are at an efficient volume 1012 on the
pressure volume curve 1010.
[0037] Stimulation may be provided on a sustained or intermittent
basis. Stimulation may be provided when a patient is asleep or
awake. In accordance with one aspect of the invention, stimulation
is provided to compensate for lung volume lost at the onset of
sleep or during sleep. In accordance with one aspect of the
invention the stimulator may be turned on by the patient prior to
sleeping or may be triggered by a sensed parameter or real time
clock. A sensor may be used to sense one or more physiological
parameters indicating onset or a specific stage of sleep. Other
sensors may sense one or more conditions that may be used to
determine appropriate times or parameters for stimulation.
[0038] In accordance with another aspect of the invention
stimulation is provided to control breathing to reduce respiration
rate and thereby improve, prevent or slow cardiac disease by
reducing hypertension, reducing sympathetic nerve activation,
providing SaO2 levels, and/or increasing cardiac output. It is
believed that lowering breathing rate will provide a decrease in
cardiac rate, and an enhanced vagal response.
[0039] In accordance with one aspect of the invention, breathing
rate may be controlled by augmenting breathing or stimulating
during intrinsic breathing to increase peak tidal volume and/or to
increase inspiration duration. Increasing the duration of
inspiration or tidal volume it is believed will cause the timing of
the next intrinsic breath to be delayed due to the central nervous
controller tendency to maintain minute ventilation in absence of
any change at the chemoreceptor level. The rate may be continuously
slowed by detecting each intrinsic breath and providing stimulation
or augmenting until the duration of inspiration, tidal volume or
exhalation rate is at a level that brings the breathing rate to a
desired rate which is reduced by the central nervous control of
minute ventilation.
[0040] FIGS. 2A to 2C illustrate stimulation during intrinsic
breathing in accordance with one aspect of the invention. FIG. 2A
illustrates flow for breaths 201, 202, 203, 204 and 205. FIG. 2B
illustrates tidal volume of breaths 201, 202, 203, 204, and 205.
Breaths 201, 202 are intrinsic breaths. Breaths 203, 204, and 205
are intrinsic breaths that are augmented by stimulation configured
to elicit a diaphragm response as illustrated schematically by
stimulation markers 213, 214, and 215.
[0041] Stimulation is initiated at a period of time during
inspiration and is provided for a period a time in a manner
configured to increase tidal volume. Stimulation during intrinsic
breathing, and augmenting breathing are described in one or more
related applications as set forth herein which are incorporated
completely and without limitation herein by reference. The tidal
volume TV.sub.2 of the breaths 203, 204, 205 where inspiration is
augmented is greater than the tidal volume TV.sub.1 of the
intrinsic, breaths 201, 202. According to one variation, the peak
flow during stimulation Pf.sub.2 may be configured as shown to be
close to the peak flow Pf.sub.1 during intrinsic breathing. The
inspiration duration TI.sub.1 of intrinsic breathing is shorter
than the inspiration duration TI.sub.2 of augmented breaths 203,
204, 205. The duration TD.sub.1 of intrinsic breathing is increased
to duration TD.sub.2 and with stimulation signals 213 214, 215, to
achieve a desired rate.
[0042] In accordance with another aspect of the invention,
stimulation during intrinsic breathing may be provided to inhibit
onset of inspiration. According to an aspect, stimulation may be
provided during exhalation to inhibit onset of an inspiration
thereby slowing breathing rate. According to an aspect, stimulation
may be provided to extend exhalation thereby delaying the onset of
a subsequent inspiration. According to an aspect, stimulation may
be provided at a low energy, low level or low frequency to inhibit
onset of an inspiration, thereby slowing breathing rate. Examples
of low energy, low level and/or low frequency stimulation are set
forth in the related applications herein.
[0043] The rate of intrinsic breathing may be controlled by
delaying intrinsic breaths with low energy (for example a lower
amplitude, frequency and/or pulse width than desired for paced
breathing) diaphragm stimulation provided during intrinsic
breathing.
[0044] According to one aspect, low energy stimulation may be
provided during intrinsic breathing, delaying onset of the next
breath and thereby slowing breathing rate. According to another
aspect, stimulation may be initiated sufficiently prior to the
onset of the next breath so as to reduce the likelihood that the
stimulation would trigger a breath. A combination of lower energy
stimulation and timing the stimulation sufficiently prior to the
onset of the next breath may be used to slow breathing rate.
[0045] FIGS. 3A to 3D illustrate stimulation provided to slow
breathing in accordance with one aspect of the invention. FIG. 3A
illustrates intrinsic diaphragm EMG activity corresponding to
breaths 301 through 307. FIGS. 3B and 3C respectively illustrate
flow and tidal volume corresponding to breaths 301 through 307.
FIG. 3D illustrates stimulation envelopes corresponding to
stimulation signals 313, 314, 315, 316, and 317 provided prior to
onset of breaths 303, 304, 305, 306, and 307 respectively.
Stimulation 313, 314, 315, 316, 317 is provided prior to the onset
of breath 303, 304, 305, 306, 307 respectively, as determined, for
example, by a model that predicts the onset of breathing or by the
actual detection of the intrinsic diaphragm EMG activity (FIG. 3A).
Stimulation is sustained for a period of time. For example, the
stimulation may be provided until the onset of the intrinsic breath
is detected by the EMG signal. As illustrated, the stimulation
increases the duration of a respiration cycle T2 with respect to
the duration T1 of an intrinsic breathing cycle. As further
illustrated, intrinsic breathing cycles 303 to 307 may have greater
flow or tidal volume to compensate for the slower breathing rate
that is induced by the stimulation.
[0046] In accordance with another aspect of the invention,
stimulation to increase tidal volume or inspiration duration may be
provided in combination with stimulation during exhalation to
inhibit the onset of the next inspiration.
[0047] In accordance with another aspect of the invention
stimulation may be provided to delay exhalation by stimulating at
the end of inspiration at a level that slows exhalation. Such
stimulation may be provided by stimulating during intrinsic
breathing or by providing paced breathing for example that
maintains minute ventilation while providing a slower rate of
breathing.
[0048] FIGS. 4A-4C illustrate stimulation during intrinsic
breathing in accordance with one aspect of the invention. FIG. 4A
illustrates flow for breaths 401, 402, 403, 404 and 405. FIG. 4B
illustrates tidal volume of breaths 401, 402, 403, 404 and 405.
Breaths 401, 402 arc intrinsic breaths. Breaths 403, 404, and 405
are intrinsic breaths that axe augmented by stimulation configured
to elicit a diaphragm response as illustrated schematically by
stimulation markers 413, 414, and 415. Stimulation is initiated at
a period of time at the end of inspiration and is provided for a
period a time through the exhalation period. Detection and
stimulation techniques are set forth, for example in related
applications hereto. Stimulation may be provided at a low energy
level including at a low frequency. Stimulation during intrinsic
breathing and augmenting breathing, low level and/or low frequency
are described in one or more related applications as set forth
herein which are incorporated completely and without limitation
herein by reference. The peak flow during stimulation Pf.sub.b may
be greater than the peak flow Pf.sub.a during intrinsic breaths
401, 402 as illustrated. The peak flow during stimulation Pf.sub.b
may be also not be greater than the peak flow Pf.sub.a during
intrinsic breaths 401, 402. Similarly tidal volume Tb is for
breaths 404, 405 after stimulation 413 and 414 respectively. Such
greater flow or tidal volume may intrinsically compensate for the
slower breathing rate that is induced by the stimulation. It is
believed that stimulation during exhalation inhibits onset of
inspiration. The stimulation also slows exhalation (i.e., during
the period which exhalation is occurring at a relatively faster
rate) so that the exhalation duration TE.sub.b during stimulation
is greater than the intrinsic exhalation duration TE.sub.a.
Exhalation is slowed by stimulation thus slowing the overall rate
of breathing. The duration of the intrinsic breathing respiration
cycle TD.sub.a is increased to duration TD.sub.b during
stimulation, thus reducing the breathing rate to a desired
rate.
[0049] Stimulation may also be provided to slow or control
breathing rate in a manner that provides a paced breath with
controlled exhalation as illustrated for example in U.S. patent
application Ser. No. 10/966,474, filed Oct. 15, 2004 and U.S.
patent application Ser. No. 10/966,472, filed on Oct. 15, 2004.
[0050] FIGS. 5A to 5C illustrate stimulation used to control
breathing, and breathing rate in accordance with the invention.
Breaths 501 and 502 are intrinsic breaths occurring at a rate such
that the duration of the respiration cycle is TDi and having tidal
volume TVi and peak flow PFi. Breaths 503, 504 and 505 are paced
breaths with higher tidal volume TVp and peak flow PFp. Peak flow
PFp may be controlled to be at a level substantially the same as,
higher, or lower than intrinsic peak flow. Paced breathing is
provided in a manner in which breathing is controlled or taken over
by stimulated breathing. Examples of techniques for controlling
breathing, respiratory drive and/or taking over breathing are set
forth in related applications incorporated completely and without
limitation herein by reference. In general greater tidal volume
permits a reduction in breathing rate or an increase in duration of
breathing cycle to TDii while maintaining minute ventilation. FIG.
5C illustrates stimulation envelopes 513, 514, 515 respectively
corresponding to stimulated breaths 503, 504, 505.
[0051] In accordance with another aspect of the invention
stimulation is provided to control minute ventilation to
therapeutically affect blood gas levels. Examples of controlling
minute ventilation are set forth for example in U.S. patent
application Ser. No. 10/966,474. Such stimulation may be provided,
for example, during sleep to thereby increase or normalize
SaO.sub.2 levels during sleep. In accordance with one aspect of the
invention minute ventilation is controlled to normalize SaO.sub.2
levels while not decreasing PaCO.sub.2 levels close to the apneic
threshold. According to this aspect minute ventilation may be
actively controlled using sensors to sense SaO.sub.2 or PaCO.sub.2
levels. Weaning off of pacing may be desirable to insure that the
intrinsic drive to breath is still present. Paced breathing may be
calibrated, for example at implant or adjusted during device use,
so that the device is able to provide the appropriate minute
ventilation at each pacing setting. This information may be
obtained for example through sleep studies where the device is
designed to provide stimulation during sleep.
[0052] In accordance with another aspect of the invention,
stimulation is provided to create a deep inspiration or an
increased tidal volume to thereby reduce sympathetic nerve bias,
improve blood gas levels, stimulate reflexes (for example the
Hering-Bruer reflex related to activating stretch receptors),
increase lung volume, normalize or reset breathing (one or more
parameters) or provide other beneficial therapies to improve
cardiovascular function or heart failure condition.
[0053] Examples of creating deep inspiration are set forth in U.S.
patent application Ser. No. 11/272,353 filed Nov. 10, 2005. While
these examples refer to using deep inspiration to treat apnea,
similar techniques for stimulation may be used to create deep
inspiration breaths for improving cardiovascular function or
treating heart failure. Stimulation may be provided during
intrinsic inspiration or in between inspiration cycles.
[0054] In accordance with another aspect of the invention
stimulation may be provided to manipulate intrathoracic pressure to
thereby produce a therapeutic effect.
[0055] According to one embodiment, stimulation is provided to
reduce intrathoracic pressure through induced contraction of the
right and/or left hemidiaphragm. It is believed that for some
patients, reduction in intrathoracic pressure may have a beneficial
effect on the patient's cardiovascular function or condition. For
example, a reduced intrathoracic pressure may increase cardiac
output at least in part through an increase in ventricular filling;
and reduce pulmonary arterial pressure in relation to atmospheric
pressure which would reduce right ventricular afterload. A reduced
intrathoracic pressure may also provide a decrease in filling
pressure in the right ventricle and may also thereby improve
systemic venous return. A reduced intrathoracic pressure may also
provide better coronary artery perfusion.
[0056] In accordance with one aspect of the invention, patients
with heart failure manifesting in poor ventricular filling may be
treated with stimulation to reduce intrathoracic pressure. In
accordance with one aspect of the invention, patients with
diastolic heart failure may be treated with stimulation to reduce
intrathoracic pressure. In accordance with another aspect of the
invention stimulation to reduce intrathoracic pressure may be
provided to patients who are hypovolemic where the therapeutic
effects of improved ventricular filling and venous return would be
particularly beneficial.
[0057] According one aspect of the invention stimulation is
provided to elicit a diaphragm response to cause a reduced
intrathoracic pressure. The stimulation is provided at a level that
does not elicit a breath, in other words, where intrinsic breathing
continues to occur. Examples of stimulation such as bias
stimulation and low energy or low frequency stimulation are
described in related applications set forth herein. The stimulation
eliciting a reduced intrathoracic pressure may be sustained or
intermittent. Stimulation is preferably provided when a patient is
sleeping but may also be provided when a patient is awake.
[0058] In accordance with one aspect of the invention, stimulation
may be provided to one hemidiaphragm to elicit a change in
intrathoracic pressure in the respective side of the thoracic
cavity. For example the right hemidiaphragm may be stimulated to
cause a reduced intrathoracic pressure primarily in the right
thoracic cavity to thereby effect the right side of the heart to a
greater degree than the left. Or stimulating unilaterally on die
diaphragm may serve to minimize the pressure changes that the heart
is exposed to. This may be beneficial when an increased lung volume
is desired to treat OSA or CSA. Sensors may be used to sense
arterial and venous blood volume so that stimulation may be
adjusted based on patient's blood volume state. For example,
stimulation may be increased or turned on when the patient is in a
hypovolemic state where in a particular patient a greater benefit
would be produced with a more negative intrathoracic pressure. Such
sensors may include, for example, impedance (plethysmography)
sensors used to monitor fluid levels in the body. Separate
electrodes, or existing stimulation electrodes may be used in a
configuration or with frequencies that can determine resistance
and/or reactance. Fluid volume changes may, for example, be
monitored based on a baseline established with the sensors and a
hyper or hypo volemic state may be detected.
[0059] In accordance with another aspect of the invention,
stimulation is provided to elicit a diaphragm response that
improves heart failure as described above in combination with
treating sleep disorders that contribute to or worsen heart
failure. Accordingly, stimulation is provided as described in the
related patent applications set forth herein, to elicit a diaphragm
response to thereby reduce breathing disorders to thereby improve
condition of a heart failure patient. One or more specific methods
of reducing sleep disordered breathing events and preventing sleep
disordered breathing are described in related applications as set
forth herein.
[0060] In accordance with one aspect of the invention, stimulation
is provided prior to a physiological trigger of a central or
obstructive sleep apnea event in a manner that reduces the
occurrence of such events, thus reducing the effects of apnea
events that worsen heart failure.
[0061] In accordance with another aspect of the invention a
combined cardiac rhythm management device and diaphragm/phrenic
nerve stimulation device is provided to provide an enhanced
combined treatment device. In accordance with this aspect of the
invention, the diaphragm stimulation element may comprise an
abdominally placed stimulator positioned on the diaphragm or
phrenic nerve, a thoracoseopically placed stimulator positioned on
the diaphragm or phrenic nerve, a phrenic nerve stimulator
positioned in the neck region on or adjacent the phrenic nerve
(transcutaneous, percutaneous, or otherwise implanted);
transcutaneous stimulation of the diaphragm through leads at or
near the ziphoid region (this may be in combination with a
defibrillator function or device that is configured for
subcutaneous stimulation of the heart); or a pectorally positioned
lead, for example, placed transvenously.
[0062] The system may be further enhanced through the ability to
avoid negative device/device interactions where a separate
controller is used, e.g. for a CRT, pacemaker. ICD or other
therapeutic electrical stimulation device. The system may also
provide arrhythmia and sleep disorder detection algorithms through
sensing of both the cardiac and respiration cycles.
[0063] The system may also be included in a combination with a CRM
device having a common controller.
* * * * *