U.S. patent application number 12/724723 was filed with the patent office on 2010-07-08 for therapy triggered by predication of disordered breathing.
Invention is credited to Douglas R. Daum, Jesse Hartley, John D. Hatlestad, Kent Lee, Quan Ni, Jeffrey E. Stahmann.
Application Number | 20100174335 12/724723 |
Document ID | / |
Family ID | 34193807 |
Filed Date | 2010-07-08 |
United States Patent
Application |
20100174335 |
Kind Code |
A1 |
Stahmann; Jeffrey E. ; et
al. |
July 8, 2010 |
Therapy Triggered by Predication of Disordered Breathing
Abstract
An approach to providing disordered breathing therapy includes
providing therapy based on a prediction of disordered breathing.
One or more patient conditions are detected and used to predict
disordered breathing. Therapy is delivered to mitigate the
predicted disordered breathing. The disordered breathing therapy
may be adapted to enhance therapy efficacy and/or to reduce the
impact of the therapy to the patient.
Inventors: |
Stahmann; Jeffrey E.;
(Ramsey, MN) ; Hatlestad; John D.; (Maplewood,
MN) ; Ni; Quan; (Shoreview, MN) ; Hartley;
Jesse; (Lino Lakes, MN) ; Daum; Douglas R.;
(Woodbury, MN) ; Lee; Kent; (Shoreview,
MN) |
Correspondence
Address: |
HOLLINGSWORTH & FUNK
8500 Normandale Lake Blvd, SUITE 320
MINNEAPOLIS
MN
55437
US
|
Family ID: |
34193807 |
Appl. No.: |
12/724723 |
Filed: |
March 16, 2010 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
10643154 |
Aug 18, 2003 |
7680537 |
|
|
12724723 |
|
|
|
|
Current U.S.
Class: |
607/20 |
Current CPC
Class: |
A61N 1/3702 20130101;
A61N 1/3621 20130101; A61N 1/3627 20130101; A61N 1/36514
20130101 |
Class at
Publication: |
607/20 |
International
Class: |
A61N 1/365 20060101
A61N001/365 |
Claims
1. A method of providing disordered breathing therapy to a patient,
comprising: detecting via a detector system one or more conditions
associated with disordered breathing of a patient; predicting
disordered breathing based on the one or more detected conditions
using at least a first disordered breathing prediction criteria
set; estimating an accuracy of the first disordered breathing
prediction criteria set; adapting a therapy for the patient to
mitigate the predicted disordered breathing; and delivering the
adapted therapy to the patient via a therapy delivery system,
wherein at least one of predicting, adapting, and delivering is
performed at least in part implantably.
2. The method of claim 1, wherein each of predicting, adapting, and
delivering is performed at least in part implantably.
3. The method of claim 1, further comprising: using a first group
of the one or more detected conditions for predicting disordered
breathing; and using a second group of the detected conditions for
adapting the therapy to mitigate the predicted disordered
breathing.
4. The method of claim 3, wherein the one or more detected
conditions comprises any combination of a physiological condition
and a contextual condition.
5. The method of claim 3, wherein the second group of the detected
conditions comprises one or more of: a condition used to assess an
impact of the therapy on the patient a condition used to assess
therapy efficacy, a condition associated with sleep quality, a
condition associated with patient comfort, a condition used to
assess respiration quality, a cardiovascular system condition, a
respiratory system condition, a nervous system condition, a blood
chemistry condition, and a muscle system condition.
6. The method of claim 1, wherein adapting the therapy comprises
adapting the therapy based on one or more of patient therapy
interactions and detection of one or more episodes of disordered
breathing.
7. The method of claim 6, wherein the detection of the one or more
episodes of disordered breathing comprises detecting any
combination of a severity, a duration, and a frequency of the one
or more detected episodes of disordered breathing.
8. The method of claim 1, wherein adapting the therapy comprises
adapting the therapy to perform any combination of terminating and
preventing the predicted disordered breathing.
9. The method of claim 1, wherein adapting the therapy comprises
adapting a cardiac pacing therapy.
10. The method of claim 9, wherein adapting the cardiac pacing
therapy comprises adapting any combination of atrial pacing
therapy, ventricular pacing therapy, multi-chamber pacing
therapy.
11. The method of claim 9, wherein adapting the cardiac pacing
therapy comprises any combination of adapting the cardiac pacing
therapy at a rate above an intrinsic rate, adapting the cardiac
pacing therapy at a rate above a normally programmed pacing rate,
switching pacing sites, and switching pacing modes.
12. A medical device, comprising: a detector system configured to
detect one or more conditions associated with disordered breathing
of a patient; a prediction engine coupled to the detector system
and configured to: predict disordered breathing based on the
detected conditions using at least a first disordered breathing
prediction criteria set; estimate an accuracy of the first
disordered breathing prediction criteria set; and adapt a therapy
for the patient to mitigate the predicted disordered breathing; and
a therapy delivery system coupled to the prediction engine and the
detector system and configured to deliver the adapted therapy to
the patient, wherein the prediction engine includes an implantable
component.
13. The medical device of claim 12, wherein one or both of the
therapy delivery system and the detector system include implantable
components.
14. The medical device of claim 12, wherein the prediction engine
is further configured to: use a first group of the one or more
detected conditions for predicting disordered breathing; and use a
second group of the detected conditions for adapting the therapy to
mitigate the predicted disordered breathing.
15. The medical device of claim 14, wherein the one or more
conditions comprise any combination of a physiological condition
and a contextual condition.
16. The medical device of claim 14, wherein the second group of the
detected conditions comprises one or more of: a condition used to
assess an impact of the therapy on the patient a condition used to
assess therapy efficacy, a condition associated with sleep quality,
a condition associated with patient comfort, a condition used to
assess respiration quality, a cardiovascular system condition, a
respiratory system condition, a nervous system condition, a blood
chemistry condition, and a muscle system condition.
17. The medical device of claim 12, wherein adapting the therapy
comprises adapting the therapy based on one or more of patient
therapy interactions and detection of one or more episodes of
disordered breathing.
18. The medical device of claim 12, wherein adapting the therapy
comprises adapting the therapy to perform any combination of
terminating and preventing the predicted disordered breathing.
19. The medical device of claim 12, wherein adapting the therapy
comprises adapting a cardiac pacing therapy.
20. The medical device of claim 12, wherein the prediction engine
is configured to perform real-time prediction of the disordered
breathing.
Description
RELATED PATENT DOCUMENTS
[0001] This is a divisional of U.S. patent application Ser. No.
10/643,154, filed on Aug. 18, 2003, to which Applicant claims
priority under 35 U.S.C. .sctn.120, and which is incorporated
herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to providing therapy
for disordered breathing based on prediction of disordered
breathing.
BACKGROUND OF THE INVENTION
[0003] Disordered breathing refers to a wide spectrum of
respiratory conditions that involve disruption of the normal
respiratory cycle. Although disordered breathing typically occurs
during sleep, the condition may also occur while the patient is
awake. Respiratory disruption can be particularly serious for
patients concurrently suffering from cardiovascular deficiencies,
such as congestive heart failure. Unfortunately, disordered
breathing is often undiagnosed. If left untreated, the effects of
disordered breathing may result in serious health consequences for
the patient.
[0004] Various types of disordered respiration have been
identified, including, for example, apnea, hypopnea, dyspnea,
hyperpnea, tachypnea, and periodic breathing, including
Cheyne-Stokes respiration (CSR). Apnea is a fairly common disorder
characterized by periods of interrupted breathing. Apnea is
typically classified based on its etiology. One type of apnea,
denoted obstructive apnea, occurs when the patient's airway is
obstructed by the collapse of soft tissue in the rear of the
throat. Central apnea is caused by a derangement of the central
nervous system control of respiration. The patient ceases to
breathe when control signals from the brain to the respiratory
muscles are absent or interrupted. Mixed apnea is a combination of
the central and obstructive apnea types. Regardless of the type of
apnea, people experiencing an apnea event stop breathing for a
period of time. The cessation of breathing may occur repeatedly
during sleep, sometimes hundreds of times a night and sometimes for
a minute or longer.
[0005] In addition to apnea, other types of disordered respiration
have been identified, including hypopnea (shallow breathing),
tachypnea (rapid breathing), hyperpnea (heavy breathing), and
dyspnea (labored breathing). Combinations of the respiratory cycles
described above may be observed, including, for example, periodic
breathing and Cheyne-Stokes breathing. Periodic breathing is
characterized by cyclic respiratory patterns that may exhibit
rhythmic rises and falls in tidal volume. Cheyne-Stokes respiration
is a specific form of periodic breathing wherein the tidal volume
decreases to zero resulting in apneic intervals. The breathing
interruptions of periodic breathing and CSR may be associated with
central apnea, or may be obstructive in nature. CSR is frequently
observed in patients with congestive heart failure (CHF) and is
associated with an increased risk of accelerated CHF progression.
Because of the cardiovascular implications, therapy for
respiration-related sleep disorders is of particular interest.
SUMMARY OF THE INVENTION
[0006] Various embodiments of present invention involve methods and
systems for providing disordered breathing therapy based on
prediction of disordered breathing.
[0007] In accordance with an embodiment of the invention, a method
of providing therapy for disordered breathing involves detecting
one or more conditions associated with disordered breathing and
predicting disordered breathing based on the one or more detected
conditions. Therapy to mitigate the predicted disordered breathing
is delivered. At least one of detecting the conditions, predicting
the disordered breathing, and delivering the therapy is performed
at least in part implantably.
[0008] In accordance with a further embodiment of the invention, a
method of providing disordered breathing therapy involves
predicting disordered breathing and adapting a therapy to mitigate
the disordered breathing. The adapted therapy is delivered to the
patient. At least one of predicting the disordered breathing,
adapting the therapy, and delivering the adapted therapy is
performed at least in part implantably.
[0009] Yet another embodiment of the invention includes a medical
device for providing disordered breathing therapy. The medical
device includes a detector system configured to detect one or more
conditions associated with disordered breathing. A prediction
engine is coupled to the detector system and is configured to
predict disordered breathing based on the one or more detected
conditions. A therapy delivery system is coupled to the prediction
engine and is configured to delivery therapy to the patient to
mitigate the predicted disordered breathing.
[0010] A further embodiment of the invention involves a disordered
breathing therapy system including means for detecting one or more
conditions associated with disordered breathing and means for
predicting disordered breathing based on the detected conditions.
The system further includes means for delivering therapy to
mitigate the predicted disordered breathing. At least one of the
means for detecting the one more conditions, the means for
predicting disordered breathing, and the means for delivering
therapy includes an implantable component.
[0011] Yet another embodiment of the invention involves a system
for providing therapy for disordered breathing. The system includes
means for predicting disordered breathing and means for adapting a
therapy to mitigate the predicted disordered breathing. The system
further includes means for delivering the adapted therapy to the
patient. At least one of the means for predicting disordered
breathing, the means for adapting a therapy to mitigate the
disordered breathing, and the means for delivering the adapted
therapy to the patient includes an implantable component.
[0012] The above summary of the present invention is not intended
to describe each embodiment or every implementation of the present
invention. Advantages and attainments, together with a more
complete understanding of the invention, will become apparent and
appreciated by referring to the following detailed description and
claims taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a flow graph illustrating a method for providing
disordered breathing therapy in accordance with embodiments of the
invention;
[0014] FIG. 2 is a block diagram of a disordered breathing therapy
system in accordance with embodiments of the invention;
[0015] FIG. 3 illustrates conditions that may be used to predict
disordered breathing according to embodiments of the invention;
[0016] FIG. 4 is a block diagram of a disordered breathing
prediction engine in accordance with embodiments of the
invention;
[0017] FIG. 5 is a flow graph illustrating a method of updating a
prediction criteria library according to embodiments of the
invention;
[0018] FIG. 6 is a block diagram of a cardiac rhythm management
system incorporating a disordered breathing prediction engine in
accordance with embodiments of the invention;
[0019] FIG. 7 is a diagram illustrating a system for predicting
disordered breathing in accordance with embodiments of the
invention;
[0020] FIG. 8A illustrates a representative graph of tidal volume
signal used in connection with disordered breathing prediction in
accordance with embodiments of the invention;
[0021] FIG. 8B illustrates a representative graph of heart rate
signal used in connection with disordered breathing prediction in
accordance with embodiments of the invention;
[0022] FIG. 8C illustrates a representative graph of an activity
signal used in connection disordered breathing prediction in
accordance with embodiments of the invention;
[0023] FIG. 9 is a flow graph of a method for delivering an adapted
therapy for disordered breathing in accordance with embodiments of
the invention;
[0024] FIG. 10 illustrates adjustment of an activity sleep
threshold using an MV condition in accordance with embodiments of
the invention;
[0025] FIG. 11 illustrates a normal respiration pattern as
represented by a transthoracic impedance sensor signal;
[0026] FIG. 12 illustrates respiration intervals used for
disordered breathing detection according to embodiments of the
invention;
[0027] FIG. 13 illustrates detection of sleep apnea and severe
sleep apnea according to embodiments of the invention;
[0028] FIGS. 14A-14B are graphs of tidal volume derived from
transthoracic impedance measurements according to embodiments of
the invention;
[0029] FIG. 15 is a flow graph illustrating a method of apnea and
hypopnea detection according to embodiments of the invention;
[0030] FIG. 16 is a graph illustrating a breathing interval
according to embodiments of the invention;
[0031] FIG. 17 is a graph illustrating a hypopnea detection
approach in accordance with embodiments of the invention;
[0032] FIGS. 18A-18B are charts illustrating disordered breathing
events that can be addressed in accordance with embodiments of the
invention;
[0033] FIGS. 18C-18G are graphs illustrating disordered breathing
events comprising a mixture of apnea and hypopnea respiration
cycles;
[0034] FIG. 19 is a flow graph of a method for detecting disordered
breathing by classifying breathing patterns in accordance with
embodiments of the invention;
[0035] FIG. 20 is a block diagram illustrating a system for
adapting a therapy to mitigate disordered breathing based on
therapy efficacy and minimal impact to the patient; and
[0036] FIG. 21 is a flow graph of a method of adapting a therapy
for disordered breathing using disordered breathing detection and
sleep quality assessment.
[0037] While the invention is amenable to various modifications and
alternative forms, specifics thereof have been shown by way of
example in the drawings and will be described in detail below. It
is to be understood, however, that the intention is not to limit
the invention to the particular embodiments described. On the
contrary, the invention is intended to cover all modifications,
equivalents, and alternatives falling within the scope of the
invention as defined by the appended claims.
DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS
[0038] In the following description of the illustrated embodiments,
references are made to the accompanying drawings which form a part
hereof, and in which are shown by way of illustration, various
embodiments by which the invention may be practiced. It is to be
understood that other embodiments may be utilized, and structural
and functional changes may be made without departing from the scope
of the present invention.
[0039] A significant percentage of patients between the ages of 30
and 60 years experience some symptoms of disordered breathing.
Sleep disordered breathing is associated with excessive daytime
sleepiness, systemic hypertension, increased risk of stroke, angina
and myocardial infarction. Disordered breathing is particularly
prevalent among congestive heart failure patients, and may
contribute to the progression of heart failure.
[0040] Various therapies have been used to treat central and/or
obstructive disordered breathing episodes. Obstructive sleep apnea
has been associated with prolapse of the tongue and its surrounding
structure into the pharynx, thus occluding the respiratory pathway.
A commonly prescribed treatment for obstructive apnea is continuous
positive airway pressure (CPAP). A CPAP device delivers air
pressure through a nasal mask worn by the patient. The application
of continuous positive airway pressure keeps the patient's throat
open, reducing or eliminating the obstruction causing apnea.
[0041] Prolapse of the tongue muscles has been attributed to
diminishing neuromuscular activity of the upper airway. A treatment
for obstructive sleep apnea involves compensating for the decreased
muscle activity by electrical activation of the tongue muscles. The
hypoglossal (HG) nerve innervates the protrusor and retractor
tongue muscles. An appropriately applied electrical stimulation to
the hypoglossal nerve, for example, prevents backward movement of
the tongue, thus preventing the tongue from obstructing the
airway.
[0042] Cardiac stimulation may be used as a therapy for disordered
breathing. Therapy methods using cardiac pacing is described in
commonly owned U.S. Publication No. 2005/0039745, filed
concurrently with this patent application, and incorporated by
reference herein in its entirety. The cardiac pacing method
described uses an adaptive therapy based on detection of disordered
breathing. Such a disordered breathing therapy may be adapted, for
example, to achieve an overall level of therapy efficacy, patient
comfort, sleep quality, interaction with other patient therapies,
or device service life.
[0043] Embodiments of the invention discussed herein relate to
systems and methods providing an adaptive therapy for disordered
breathing based on prediction of disordered breathing. Various
approaches for predicting disordered breathing are described in
commonly owned U.S. Pat. No. 7,396,333 and incorporated by
reference herein in its entirety.
[0044] The flowchart of FIG. 1 illustrates a method for triggering
disordered breathing therapy based on a prediction of disordered
breathing according to various embodiments of the invention. The
method involves detecting 110 conditions associated with disordered
breathing and predicting disordered breathing 120 based on the
detected conditions. Disordered breathing may be predicted, for
example, by comparing the detected conditions to disordered
breathing prediction criteria. A representative set of conditions
that may be used to predict disordered breathing are listed in
Table 1. The representative set of conditions listed in Table 1 is
not exhaustive, and conditions other than those listed may be used
to predict disordered breathing. If disordered breathing is
predicted, therapy is delivered 130 to mitigate the disordered
breathing, e.g., reduce the severity of the disordered breathing or
prevent the disordered breathing from occurring. One or more of
detecting the patient conditions, predicting the disordered
breathing based on the detected patient conditions and delivering
the therapy to mitigate the disordered breathing is performed as
least in part implantably. Implantably performing an operation
comprises performing the operation by a process that is performed
at least partially within the patient's body, or by using a
component, device, or system that is implantable within the
patient's body.
[0045] Patient conditions used in the disordered breathing
prediction may be physiological or contextual (e.g.
non-physiological). The physiological conditions may include a
broad category of conditions associated with the internal
physiological conditions of the patient. Physiological conditions
may be further subdivided, for example, into conditions of the
cardiovascular, respiratory, and nervous systems, as well as
conditions relating to the blood chemistry of the patient. In
connection with the prediction of sleep disordered breathing, an
additional physiological category associated with the patient's
sleep quality may also be defined.
[0046] Contextual conditions generally encompass the external
conditions affecting the patient. Contextual conditions may be
broadly defined to include, for example, non-physiological
environmental conditions such as temperature, humidity, air
pollution index, ambient noise, and barometric pressure as well as
body-related conditions such as patient location, posture, and
altitude. Contextual conditions may also include historical
conditions relating to the patient, including the patient's normal
sleep time and the patient's medical history, for example. Methods
and systems for detecting contextual conditions are described in
commonly owned U.S. Pat. No. 7,400,928, and incorporated by
reference herein in its entirety. Methods and systems for REM sleep
detection are described in commonly owned U.S. Publication No.
2005/0043652, incorporated herein by reference.
[0047] Table 1 provides a representative set of patient conditions
that may be used in connection with prediction of disordered
breathing, along with example sensing methods that may be employed
to detect the conditions.
TABLE-US-00001 TABLE 1 Sensor type or Detection Condition Type
Condition method Physiological Cardiovascular System Heart rate
EGM, ECG Heart rate variability QT interval Ventricular filling
pressure Intracardiac pressure sensor Blood pressure Blood pressure
sensor Respiratory System Snoring Accelerometer Microphone
Respiration pattern Transthoracic impedance (Tidal volume Minute
ventilation sensor (AC) Respiratory rate) Patency of upper airway
Intrathoracic impedance sensor Pulmonary congestion Transthoracic
impedance sensor (DC) Nervous System Sympathetic nerve activity
Muscle sympathetic nerve Activity sensor Brain activity EEG Blood
Chemistry CO2 saturation Blood analysis O2 saturation Blood alcohol
content Adrenalin B-type Natriutetic Peptide (BNP) C-Reactive
Protein Drug/Medication/Tobacco use Muscle System Muscle atonia EMG
sensor Eye movement EOG sensor Patient activity Accelerometer, MV,
etc. Limb movements Accelerometer Jaw movements EMG sensor
Contextual Environmental Ambient temperature Thermometer Humidity
Hygrometer Pollution Air quality website Time Clock Barometric
pressure Barometer Ambient noise Microphone Ambient light
Photodetector Body-related Posture Posture sensor Altitude
Altimeter Location GPS, proximity sensor Proximity to bed Proximity
to bed sensor Historical/Background Historical sleep time Patient
input, previously detected sleep onset times Medical history
Patient input device Age Recent exercise Weight Gender Body mass
index Neck size Emotional state Psychological history Daytime
sleepiness Patient perception of sleep quality Drug, alcohol,
nicotine use
[0048] Episodes of disordered breathing are associated with acute
physiological effects, including, for example, negative
intrathoracic pressure, hypoxia, and arousal from sleep. During
obstructive apnea, for example, the effort to generate airflow
increases. Attempted inspiration in the presence of an occluded
airway result in an abrupt reduction in intrathoracic pressure. The
repeated futile inspiratory efforts associated with obstructive
sleep apnea may trigger a series of secondary responses, including
mechanical, hemodynamic, chemical, neural, and inflammatory
responses.
[0049] Obstructive sleep apneas are terminated by arousal from
sleep several seconds after the apneic peak, allowing the
resumption of airflow. Coincident with arousal from sleep, surges
in sympathetic nerve activity, blood pressure, and heart rate
occur. The adverse effects of obstructive apnea are not confined to
sleep. Daytime sympathetic nerve activity and systemic blood
pressure are increased. There may also be a sustained reduction in
vagal tone, causing reduction in total heart rate variability
during periods of wakefulness.
[0050] Central sleep apnea is generally caused by a failure of
respiratory control signals from the brain and is a component of
Cheyne-Stokes respiration (CSR), a respiration pattern primarily
observed in patients suffering from chronic heart failure (CHF).
Cheyne-Stokes respiration is a form of periodic breathing in which
central apneas and hypopneas alternate with periods of
hyperventilation causing a waxing-waning pattern of tidal volume.
In some patients, obstructive sleep apnea and central sleep apnea
may coexist. In these patients, there is generally a gradual shift
from predominantly obstructive apneas at the beginning of the night
to predominantly central apneas at the end of the night.
[0051] When CHF patients lie down, the prone posture may create
central fluid accumulation and pulmonary congestion causing the
patient to reflexively hyperventilate. Central apnea is usually
initiated during sleep by an increase in ventilation and a
reduction of arterial partial pressure of carbon dioxide
(PaCO.sub.2) that is triggered by spontaneous arousal. When
PaCO.sub.2 falls below the threshold level required to stimulate
breathing, the central drive to the respiratory muscles and airflow
cease, and central apnea ensues. Apnea persists until PaCO.sub.2
rises above the threshold required to stimulate ventilation.
[0052] Arousals are not required in central sleep apneas for the
resumption of breathing at the termination of the apneic event. In
central apnea, the arousals follow the initiation of breathing and
facilitate the development of oscillations in ventilation by
recurrently stimulating hyperventilation and reducing PaCO.sub.2
below the apneic threshold. Once triggered, the pattern of
alternating hyperventilation and apnea is sustained by the
combination of increased respiratory drive, pulmonary congestion,
arousals, and apnea-induced hypoxia causing PaCO.sub.2 oscillations
above and below the apneic threshold. Shifts in the patient's state
of consciousness, particularly with repeated arousals, may further
destabilize breathing.
[0053] With the transition from wakefulness to NREM sleep the
waking neural drive to breathe is lost, and the threshold for a
ventilatory response to CO.sub.2 is increased. Therefore, if the
patient's PaCO.sub.2 level during wakefulness is below this higher
sleeping threshold, the transition to NREM sleep may be accompanied
by a transient loss of respiratory drive resulting in a central
apnea. During the apnea, the PaCO.sub.2 rises until it reaches the
new higher threshold level and initiates breathing. If sleep
becomes firmly established, regular breathing resumes. However, if
an arousal should occur, the increased PaCO.sub.2 level associated
with sleep is now relatively too high for a state of wakefulness
and will stimulate hyperventilation. Thus, although arousals
terminate obstructive sleep apneas, arousals trigger the
respiratory oscillations associated with central apneas,
particularly Cheyne-Stokes respiration.
[0054] In addition to the acute responses to central sleep apnea
discussed above, central sleep apnea is also associated with a
number of secondary responses, including, for example, decreased
HRV, and blood pressure changes. Patients with central sleep apnea
may have higher urinary and circulating norepinephrine
concentrations and lower PaCO.sub.2 during both sleep and
wakefulness.
[0055] FIG. 2 illustrates a block diagram of a disordered breathing
therapy system configured in accordance with embodiments of the
invention. It is understood that configurations, features, and
combinations of features described herein can be implemented in a
wide range of medical devices, and that such embodiments and
features are not limited to the particular devices described
herein.
[0056] The system may use patient-internal sensors 210, implanted
within the body of the patient, to detect physiological conditions.
For example, the system may determine heart rate, heart rate
variability, respiration cycles, tidal volume, and/or other
physiological signals using an intracardiac electrocardiogram (EGM)
signal detector and transthoracic impedance sensor that are part of
an implanted cardiac rhythm management system such as a cardiac
pacemaker or defibrillator.
[0057] The system may use patient-external sensors 220 to detect
physiological or contextual conditions. In one scenario, whether
the patient is snoring may be useful in predicting disordered
breathing. Snoring may be detected using an external microphone or
an implanted accelerometer. In another situation, temperature and
humidity may be factors in the patient's disordered breathing.
Signals from temperature and humidity sensors may be used to aid in
the prediction of disordered breathing.
[0058] Additionally, the system may use information input 230 by
the patient to inform the disordered breathing prediction system of
one or more patient conditions. In various embodiments, the
patient's medical history, self-described medication use, alcohol
or tobacco use, day-time sleepiness, or perceptions of sleep
quality over the past one or more sleep periods may be useful in
connection with the disordered breathing prediction.
[0059] Signals from one or more of the patient-internal sensors
210, patient-external sensors 220, and patient input devices 230
may be coupled to a disordered breathing prediction engine 240 for
prediction evaluation. In one implementation, the prediction engine
240 may compare the patient conditions to one or more sets of
disordered breathing criteria and predict disordered breathing
based on the comparison. The prediction engine 240 is coupled to a
therapy module 250. If disordered breathing is predicted, the
therapy module 250 delivers an appropriate therapy to the patient
to mitigate the disordered breathing.
[0060] In one example, the patient conditions may be sensed and
processed using implantable sensors 210, and the prediction
analysis and therapy delivery may be performed by a
patient-external disordered breathing prediction engine 240 and a
patient-external therapy module 250. Some or all of the implantable
sensors 210 may have remote communication capabilities, such as a
wireless proprietary or a wireless Bluetooth communications link.
In this implementation, the wireless communications link couples
the implantable sensor or sensors 210 to the patient-external
disordered breathing prediction engine 240. Electrical signals
representing patient conditions are produced by the implantable
sensors 210 and transmitted to the patient-external disordered
breathing prediction engine 240.
[0061] In another example, an implantable therapy device may
incorporate a disordered breathing prediction engine 240 and one or
more patient-external sensors 220. Signals representing the patient
conditions may be transmitted from the patient-external sensors to
the implanted prediction engine 240 over a wireless communication
link.
[0062] In a further example, the prediction engine may be a
patient-external device coupled wirelessly to the therapy module.
Various combinations of wireless or wired connections between the
patient-internal sensors 210, patient-external sensors 220, patient
input devices 230, the prediction engine 240, and the therapy
module 250 are possible.
[0063] The above examples provide a few of the many possible
configurations that may be used to provide disordered breathing
therapy based on the prediction of disordered breathing in
accordance with various embodiments of the invention. It is
understood that the components and functionality depicted in the
figures and described herein can be implemented in hardware,
software, or a combination of hardware and software. It is further
understood that the components and functionality depicted as
separate or discrete blocks/elements in the figures can be
implemented in combination with other components and functionality,
and that the depiction of such components and functionality in
individual or integral form is for purposes of clarity of
explanation, and not of limitation.
[0064] The methods and systems for predicting disordered breathing
and providing therapy for disordered breathing as illustrated by
the embodiments described herein may be used in cooperation with
advanced patient management systems. Advanced patient management
systems allow physicians to remotely and automatically monitor
patient conditions and test physiological functions, including
cardiac and respiratory functions, for example. In one example of
advanced patient management, an implantable cardiac rhythm
management system, such as cardiac monitor, pacemaker,
defibrillator, or cardiac resynchronization device, may be equipped
with various telecommunications and information technologies
enabling real-time data collection, diagnosis, and treatment of the
patient. Advanced patient management systems may be enhanced by
real-time prediction of disordered breathing and/or long term
collection of disordered breathing prediction data. Systems and
methods involving advanced patient management techniques are
described in U.S. Pat. Nos. 6,336,903, 6,312,378, 6,270,457, and
6,398,728 which are incorporated herein by reference in their
respective entireties.
[0065] One subset of the detected patient conditions, such as the
representative conditions listed in Table 1, may represent
conditions that predispose the patient to disordered breathing.
Predisposing conditions may be statistically associated with an
onset of disordered breathing during the next few hours following
the detection of the conditions leading to the disordered breathing
prediction. Another subset of conditions may represent precursor
conditions used to predict an imminent onset of disordered
breathing that may occur within a time window measured in terms of
a few minutes or seconds. Detection of patient conditions
associated with disordered breathing and prediction of disordered
breathing based on predisposing or precursor conditions is
performed on real-time basis.
[0066] A subset of patient conditions may be used to verify or
otherwise inform the disordered breathing prediction. In one
example, information regarding sleep onset or sleep state, e.g.,
REM or non-REM sleep, may be employed in prediction of sleep
disordered breathing. A subset of the conditions listed in Table 1
may be used to detect whether the patient is asleep and to track
the various stages of sleep. Another subset of the conditions may
be employed to detect and classify disordered breathing episodes.
Table 2 below provides further examples of how some conditions
listed in Table 1 may be used in disordered breathing
prediction.
TABLE-US-00002 TABLE 2 Condition Examples of how condition is used
in disordered breathing prediction Heart rate Decrease in heart
rate may indicate disordered breathing episode. Decrease in heart
rate may indicate the patient is asleep. Heart rate variability May
be used to determine sleep state and reduction in heart rate
variability is a chronic factor associated with disordered
breathing. Ventricular filling pressure May be used to
identify/predict pulmonary congestion associated with respiratory
disturbance. Blood pressure Swings in on-line blood pressure
measures are associated with apnea. Snoring Snoring is associated
with a higher incidence of obstructive sleep apnea and may be used
to detect disordered breathing. Respiration signals/respiration
Respiration patterns may be used to detect disordered breathing
patterns episodes. Respiration patterns may be used to determine
the type of disordered breathing. Respiration patterns may be used
to detect that the patient is asleep. Hyperventilation may be used
to predict disordered breathing. Previous episodes of disordered
breathing may be used to predict further episodes. One form of
disordered breathing may be used to predict another form of
disordered breathing Patency of upper airway Patency of upper
airway is related to obstructive sleep apnea and may be used to
detect episodes of obstructive sleep apnea. Pulmonary congestion
Pulmonary congestion is associated with respiratory disturbances.
Sympathetic nerve activity End of apnea associated with a spike in
SNA CO2 saturation Low CO2 levels initiate central apnea. O2
saturation O2 desaturation occurs during severe apnea/hypopnea
episodes. Blood alcohol content Alcohol tends to increase incidence
of snoring & obstructive apnea. Adrenalin End of apnea
associated with a spike in blood adrenaline. Brain Natriuretic
Peptide A marker of heart failure status, which is associated with
Cheyne- (BNP) Stokes Respiration C-Reactive Protein A measure of
inflammation that may be related to apnea. Drug/Medication/Tobacco
use These substances may affect the likelihood of both central
& obstructive apnea. Muscle atonia Muscle atonia may be used to
detect REM and non-REM sleep. Eye movement Eye movement may be used
to detect REM and non-REM sleep. Temperature Ambient temperature
may be a condition predisposing the patient to episodes of
disordered breathing. Humidity Humidity may be a condition
predisposing the patient to episodes of disordered breathing.
Pollution Pollution may be a condition predisposing the patient to
episodes of disordered breathing. Posture Posture may be used to
determine if the patient is asleep and may predispose the patient
to disordered breathing. Posture may be a condition predisposing
the patient to episodes of disordered breathing. Activity Patient
activity may be used in relation to sleep detection. Sleep stage
NREM sleep may be associated with a higher probability of DB
Location Patient location may used to determine if the patient is
in bed as a part of sleep detection.
[0067] FIG. 3 conceptually illustrates how patient conditions such
as those listed in Table 1 and/or 2 may be used in predicting
disordered breathing 310 according to embodiments of the invention.
In one embodiment, the system tracks one or more of the conditions
listed in Table 1, Table 2, or both, to predict disordered
breathing. For example, over the course of a period of time, e.g.,
at least a 16 hour window preceding and including the patient's
historical sleep time, the system may track one or more conditions
to determine the presence and/or level of each particular
condition.
[0068] In one implementation, the system tracks conditions that
have been determined to predispose 320 the patient to an attack of
disordered breathing. Predisposing conditions represent patient
conditions statistically associated with an onset of disordered
breathing. The presence of one or more predisposing conditions may
indicate that disordered breathing is likely to occur within the
next time period, such as an eight hour period following the
disordered breathing prediction, or during the current sleep
period. For example, the predisposing conditions may include the
air pollution index of the patient's environment downloaded from an
air quality website, recent tobacco use reported by the patient,
the degree of the patient's pulmonary congestion detected by an
implanted transthoracic impedance sensor, as well as other patent
internally or externally detected predisposing conditions.
[0069] Additionally, or alternatively, the system may use previous
episodes of disordered breathing to determine that the patient is
predisposed to further episodes of disordered breathing within
particular time period, such as during a sleep period. For example,
previous episodes of disordered breathing during a first interval
within the sleep period may be an indication that additional
episodes are likely to occur in a second and subsequent interval
within the same sleep period. In one example, the occurrence of a
first type of disordered breathing may be used to predict a second
type of disordered breathing. In another example, the periodicity
of disordered breathing may be used to predict future episodes of
disordered breathing.
[0070] The disordered breathing prediction engine may use the type,
duration, frequency, and/or severity of the previous disordered
breathing episodes to inform the disordered breathing prediction
analysis. Quantification of the severity, frequency, and duration
of disordered breathing may be accomplished using any of a number
of disturbed breathing measures, including, for example, percent
time in disordered breathing and the apnea/hypopnea index.
[0071] A further example of a condition predisposing a patient to
hypopnea or apnea is body posture. A supine posture is more likely
to result in obstruction of the upper airway and can be used to
predict episodes of obstructive hypopnea and apnea. Posture and/or
torso orientation sensing may be accomplished, for example, using
an implantable multiaxis accelerometer.
[0072] As previously discussed, sleep disordered breathing is a
prevalent form of disordered breathing. Thus, a patient may be more
likely to experience episodes of disordered breathing when the
patient is in bed sleeping. Thus, proximity to bed may be employed
as a predisposing condition to disordered breathing. The disordered
breathing therapy system may use a bed proximity sensor to detect
that the patient is in bed. Bed proximity may be detected by
placing a beacon transmitter on the patient's bed. Receiver
circuitry on or in the patient, for example, incorporated in the
patient's pacemaker, receives the beacon signal and determines that
the patient is in bed.
[0073] Conditions that predispose the patient to disordered
breathing 320 are conditions that indicate the likelihood that one
or more episodes of disordered breathing will occur during the next
time period, such as over the course of the night or other sleep
period. Based on predisposing conditions 320, an onset of
disordered breathing may be predicted 312 to occur within a time
window that may include several hours, for example, eight
hours.
[0074] A second set of conditions, denoted herein as precursor
conditions 330, may be used to predict 314 an impending onset of
disordered breathing. Precursor conditions 330 indicate that an
episode of disordered breathing is imminent and will occur within a
time window that may be measured in terms of minutes or seconds,
for example. In one implementation, precursor conditions 330 may be
used to predict that an episode of disordered breathing will occur
within the next 300 seconds, for example.
[0075] In one embodiment, precursor conditions 330 indicative of an
impending onset of disordered breathing may include, for example,
pre-apnea or pre-hypopnea conditions. In one implementation,
changes in blood gas concentration, such as CO.sub.2, may be causal
to central apnea. Therefore, a precursor condition of pre-apnea in
a particular patient may be detected when the patient's CO.sub.2
level, as measured, for example, by a patient-external CO.sub.2
sensor, falls below a selected level, indicating an impending onset
of an apnea episode.
[0076] In another embodiment, a patient's heart rate variability
may be significantly altered before, during, and after episodes of
apnea. Heart rate variability may be used, for example, as a
precursor condition to predict an impending episode of disordered
breathing.
[0077] In yet another embodiment, a pre-apnea or pre-hypopnea
condition may be detected by analyzing the patient's respiration
patterns. Respiration cycles just prior to disordered breathing
event, e.g., an apnea or hypopnea event, may exhibit a
characteristic pattern. For example, an apnea event for many
patients is preceded by a period of hyperventilation with a number
of rapid, deep breaths. The pattern of hyperventilation may be
detected by analyzing patient's transthoracic impedance signal to
determine respiration rate and tidal volume.
[0078] Cheyne-Stokes respiration and some apnea/hypopnea episodes
may exhibit a crescendo--decrescendo respiration pattern. The
crescendo--decrescendo respiration pattern produces
hyperventilation during the crescendo stage and hypoventilation
during the decrescendo phase. Hyperventilation, secondary to
pulmonary congestion, drives arterial partial pressure of carbon
dioxide down. A decrease in arterial partial pressure of carbon
dioxide below an apnea level may be a causal mechanism for central
apnea. According to one embodiment of the invention, detection of
an impending onset of disordered breathing may be implemented by
detecting a series of increasing tidal volumes followed by a series
of decreasing tidal volumes.
[0079] For some patients, disordered breathing occurs at regular
intervals, allowing the periodicity of the disordered breathing
episodes to be used as a precursor condition. If disordered
breathing episodes of the patient occur at regular intervals, the
next episode of disordered breathing may be predicted based on the
time elapsed since the last episode was detected.
[0080] In addition, the occurrence of one form of disordered
breathing may be used to predict another form of disordered
breathing. For example, a patient may characteristically experience
one or more episodes of obstructive sleep apnea during the first
part of the night followed by central sleep apnea episodes during
the later part of the night. In another example, one or more
episodes of hypopnea may be used to predict future apnea
episodes.
[0081] Snoring is an additional example of a pre-apnea or
pre-hypopnea condition. In many, patient snoring, or more generally
any abnormal airflow in the upper airway, which may be detectable
via acoustic means, precedes more significant sleep disordered
breathing conditions such as hypopnea or apnea. Precursor
conditions 330 may be analyzed individually, or in combination with
one or more predisposing conditions 320, to predict the impending
onset of a disordered breathing episode.
[0082] The conditions and associated prediction criteria used for
disordered breathing prediction may be highly patient specific.
Conditions that are reliably predictors of disordered breathing in
one patient may not be effective for another patient. Therefore,
conditions used to predict disordered breathing and the respective
prediction criteria are preferably based on patient-specific
data.
[0083] A subset of patient conditions may be used to verify or
confirm a prediction of disordered breathing. For example, before
or after a prediction of disordered breathing is made, one or more
verification conditions 340 may be checked to confirm the
prediction. The verification conditions, as well as the
physiological and contextual conditions used to predict disordered
breathing, may be highly patient specific.
[0084] In one example embodiment, a characteristic pattern of
respiration is a reliable predictor of disordered breathing in a
particular patient only when the patient is supine. If the
prediction is made while the patient not supine, normal variations
in respiration cycles in this particular patient may lead to an
erroneous prediction of disordered breathing. Thus, before
disordered breathing is predicted, a posture sensor signal is
checked to verify that the patient is supine. If the patient is
supine and the patient's respiration cycles are consistent with
criteria indicating that disordered breathing is likely, the
disordered breathing prediction is made.
[0085] In another example, the patient is known to suffer from
episodes of apnea during sleep. The patient's sleep apnea may be
predicted using a number of contextual and physiological
conditions. The prediction of sleep apnea may be made after
assessing that the patient's posture and location are consistent
with sleep. Before a prediction of sleep apnea is made, the system
confirms that the patient is lying down in bed by checking the
signal from an implantable posture sensor and a bed proximity
sensor.
[0086] Alternatively, or additionally, the system may detect that
the patient is sleeping by examining the patient's respiration
and/or activity prior to making a prediction regarding sleep
disordered breathing. A method of sleep detection is described in
commonly owned U.S. patent application Ser. No. 10/309,771, filed
Dec. 4, 2002, which is incorporated herein by reference in its
entirety.
[0087] The operation of a disordered breathing prediction engine
400, according various to embodiments, is conceptually illustrated
in the block diagram of FIG. 4. Periodically, one or more patient
conditions are detected and compared to a library 410 of prediction
criteria. The prediction criteria library 410 may incorporate one
or more sets of prediction criteria 411, 412, 413, 414. Each of
these sets of criteria may be compared to the detected patient
conditions. If the criteria of a prediction criteria set 411, 412,
413, 414 are substantially consistent with the patient conditions,
a preliminary disordered breathing prediction may be made.
[0088] In various embodiments, the prediction criteria sets 411,
412, 413, 414 represent one or more condition thresholds associated
with an onset of disordered breathing. In one example embodiment,
the level of one or more detected conditions may be compared to the
prediction criteria sets 411, 412 413, 414. If the levels of the
one or more conditions are substantially consistent with the
thresholds specified in a prediction criteria set 411, 412, 413,
414, a preliminary prediction of disordered breathing may be
made.
[0089] The examples that follow are described in terms of a
condition being consistent with a prediction criteria when the
condition exceeds a prediction criteria threshold. However, it will
be understood that different threshold requirements may be defined
for different conditions. For example, one condition may be defined
to be consistent with a prediction criterion when the condition
exceeds a prediction criterion threshold. Another condition may be
defined to be consistent with a prediction criterion threshold when
the condition falls below the threshold. In yet another example, a
condition may be defined to be consistent with the prediction
criterion when the condition falls within a specified range of
values. Patient conditions may be compared to prediction criteria
based on the timing, rate of change, or maximum or minimum value of
the condition, for example.
[0090] In the example provided in FIG. 4, the prediction criteria N
414 involves two contextual conditions, C1 and C2, and two
physiological conditions, P1 and P2. In this particular example, if
conditions C1, C2, P1, and P2 exceed levels Level1, Level2, Level3,
and Level4, respectively, the patient may be likely to experience
disordered breathing during the night. Therefore, when conditions
C1, C2, and P1, P2 reach the levels specified in criteria N 414,
preliminary prediction of disordered breathing is made.
[0091] In another embodiment of the invention, the relationships
between the detected conditions are analyzed to predict disordered
breathing. In this embodiment, the disordered breathing prediction
may be based on the existence and relative values associated with
two or more patient conditions. For example, if condition A is
present at a level of x, then condition B must also be present at a
level of f(x) before a disordered breathing prediction is made.
[0092] In yet another embodiment of the invention, the estimated
probability, P(C.sub.n), that disordered breathing will occur if a
particular condition level is detected may be expressed as a
function of the ratio of the number of times disordered breathing
occurred within a selected time interval following the detection of
the particular condition level to the total number of observed
occurrences of the condition level. The probability that disordered
breathing will occur, P(C.sub.n), is compared to a threshold
probability level to make the disordered breathing prediction.
Other methods of calculating the estimated probability are also
possible.
[0093] The prediction of disordered breathing may be based on the
convergence or divergence of a number of conditions occurring
within the same time period. In this situation, a composite
probability score may be computed as a combination of the
individual probabilities. In one embodiment, the probabilities are
combined by adding the condition probabilities after multiplying
each of the condition probabilities by a weighting factor. For
example, if the disordered breathing prediction is based on four
substantially simultaneous conditions, C.sub.1, C.sub.2, C.sub.3,
and C.sub.4, the total probability score PS.sub.T may be calculated
as:
PS.sub.T=A.times.P(C.sub.1)+B.times.P(C.sub.2)+C.times.P(C.sub.3)+D.time-
s.P(C.sub.4), [1]
[0094] where A, B, C, and D are scalar weighting factors that may
be used to estimate the relative importance of each of the
conditions C.sub.1, C.sub.2, C.sub.3, and C.sub.4. If the
probability score exceeds a selected prediction criteria threshold,
then disordered breathing is predicted.
[0095] Although the above process describes combining the estimated
probabilities for each condition by adding each of the estimated
probabilities, other methods are also possible. For example, a
detected patient condition may operate against a prediction of
disordered breathing. In this situation, the estimated probability,
P.sub.n(C.sub.n), that disordered breathing will not occur if a
particular condition level is detected may be expressed as a
function of the ratio of the number of times disordered breathing
did not occur within a selected time interval following the
detection of the particular condition level to the total number of
observed occurrences of the condition level. This value may be
subtracted from the total to determine the probability score.
Non-linear methods of combining the estimated probabilities to
arrive at a composite probability are also possible.
[0096] If the conditions affecting the patient are consistent with
a prediction of disordered breathing, the prediction may be
verified by comparing one or more verification conditions to
verification criteria. If the verification conditions are
consistent with the verification criteria, a prediction of
disordered breathing is made.
[0097] In the embodiments described above, predictions of
disordered breathing are based upon comparisons of one or more
patient conditions to sets of prediction criteria. The initial data
from which the initial prediction criteria sets are formed may be
derived from past observations taken from population data, or from
data collected from a particular patient. The initial prediction
criteria sets may then be modified as additional data are collected
from the patient.
[0098] In one embodiment, an estimated accuracy for the prediction
criteria is updated for every prediction event. The estimated
positive predictive value (PPV) for a prediction criteria set N may
be expressed as:
PPV N = TP TP + FP [ 2 ] ##EQU00001##
[0099] where TP (true positive) is the number of times the
prediction criteria set successfully predicted disordered
breathing, and FP (false positive) is the number of times the
prediction criteria erroneously predicted disordered breathing.
[0100] If the estimated accuracy of prediction criteria set N,
PPV.sub.N, falls below a predetermined level, for example, 0.7, the
prediction criteria set N may be modified. In one embodiment, a
possible prediction criteria set is formed, for example, by
modifying the threshold level of one or more of the conditions
represented by the original prediction criteria set N. In one
embodiment, each threshold in the original prediction criteria set
N is modified by an incremental value, to make the prediction
criteria set more accurate.
[0101] In another embodiment, conditions represented in the
original prediction criteria set N are compared to the conditions
that are present just prior to a disordered breathing occurrence to
determine how the modification for the possible prediction criteria
set should be implemented. For example, if the level of a
particular condition just prior to the occurrence shows a
relatively large variation just prior to the disordered breathing
episode, but the levels of other conditions remain constant, then
only the changing level may be modified in the possible prediction
criteria set.
[0102] Each time the possible prediction criteria set is satisfied,
no prediction of disordered breathing is made, however, the
accuracy of the possible prediction criteria set is updated, for
example, using an equation similar in form to Equation 2. If the
accuracy of the possible prediction criteria set reaches a selected
level, for example, 0.7, and the accuracy original prediction
criteria set N remains below 0.7, the possible prediction criteria
set may replace the original prediction criteria set N in the
prediction criteria library.
[0103] According to various embodiments, new prediction criteria
sets may be added to the prediction criteria library. In accordance
with these embodiments, if a disordered breathing episode occurs
without prediction, the levels of the detected patient conditions
prior to the disordered breathing episode are saved as a possible
prediction criteria set. Each time the possible prediction criteria
set is satisfied, no prediction of disordered breathing is made,
however, the accuracy of the possible prediction criteria set is
updated, for example, using an equation similar in form to Equation
2. If the accuracy of the possible prediction criteria set reaches
a selected level, for example, 0.7, the possible prediction
criteria set may be added to the prediction criteria library.
[0104] The system may also be adjusted to provide increasingly
sensitive disordered breathing prediction criteria sets, according
to various embodiments. The estimated sensitivity for a prediction
criteria set N may be expressed as:
Sensitivity N = TP TP + FN [ 3 ] ##EQU00002##
[0105] where TP (true positive) is the number of times the
prediction criteria successfully predicted disordered breathing,
and FN (false negative) is the number of times the prediction
criteria erroneously predicted that disordered breathing would not
occur.
[0106] In one embodiment, if the prediction criteria accuracy for
the prediction criteria set N becomes larger than a selected
number, for example, 0.9, then the threshold levels of one or more
of the conditions represented in the prediction criteria set N may
be adjusted to provide enhanced sensitivity.
[0107] In one example, the threshold level of each condition
represented in the prediction criteria set N is modified by an
incremental value, thus making the prediction criteria set N more
sensitive. In another embodiment, conditions represented in the
prediction criteria set N are compared to the conditions that are
present just prior to a disordered breathing occurrence to
determine how the modification of the prediction criteria set N
should be implemented. In yet another embodiment, a condition
threshold level that is modified is based upon the relative
importance of the condition in the overall prediction criteria. In
another example, if the level of a particular condition is changing
just prior to the occurrence of the disordered breathing episode,
but the levels of other conditions remain constant, only the
changing condition may be modified.
[0108] Following adjustment by any of the processes described
above, the adjusted prediction criteria set may be designated as a
possible prediction criteria set. Each time the possible prediction
criteria set is satisfied, no prediction of disordered breathing is
made, however, the accuracy of the possible prediction criteria set
is updated, for example, using Equation 2 or 3. If the accuracy of
a possible prediction criteria set reaches a selected level, for
example, 0.7, the possible prediction criteria set may be added to
the prediction criteria library.
[0109] The system may also be adjusted to provide improved
specificity or a negative predictive value (NPV) of disordered
breathing prediction criteria in a manner similar to the adaptive
method described previously. Calculation of specificity and NPV for
a prediction criteria N may be accomplished using equations 4 and 5
below.
Specificity N = TN TN + FP [ 4 ] NPV N = TN TN + FN [ 5 ]
##EQU00003##
[0110] where TN (true negative) is the number of times the
prediction criteria successfully predicted the absence of
disordered breathing, FP (false positive) is the number of times
the prediction criteria erroneously predicted disordered breathing
and FN (false negative) is the number of times the prediction
criteria erroneously predicted the absence of disordered
breathing.
[0111] The flowchart of FIG. 5 illustrates a method for
establishing and updating the prediction criteria library according
to embodiments of the invention. Previous observations of
disordered breathing may be assimilated from population data 502 or
from past observation of the specific patient 504. One or more
prediction criteria sets are determined and organized in a
prediction criteria library 506.
[0112] Conditions associated with disordered breathing are
periodically detected 508 and compared to the prediction criteria
sets in the prediction criteria library. If the conditions are
consistent 510 with any of the prediction criteria sets in the
library, then disordered breathing is predicted 515. Within a
selected time window following the disordered breathing prediction,
the system determines if disordered breathing occurs 520.
[0113] One illustrative approach to detecting disordered breathing
involves monitoring a respiratory waveform output, for example,
using a transthoracic impedance sensor. When the tidal volume (TV)
of the patient's respiration, as indicated by the transthoracic
impedance signal, falls below a hypopnea threshold, then a hypopnea
event is declared. For example, a hypopnea event may be declared if
the patient's tidal volume fall below about 50% of the recent
average tidal volume or other baseline tidal volume. When the
patient's tidal volume falls further to an apnea threshold, e.g.,
about 10% of the recent average tidal volume, an apnea event is
declared.
[0114] Other approaches to detecting disordered breathing are
described in commonly owned U.S. patent application Ser. No.
10/309,770, filed Dec. 4, 2002, which is incorporated herein by
reference in its entirety.
[0115] If disordered breathing occurs 520, the prediction criteria
accuracy of the prediction criteria set used for the disordered
breathing prediction is updated 525. If the updated prediction
criteria accuracy is greater 530 than a selected number, then a
possible prediction criteria set is formed 535. The possible
prediction criteria set may be formed, for example, by substituting
more sensitive condition levels when compared to the original
prediction criteria set.
[0116] If disordered breathing is not detected 520 following the
prediction, then the prediction criteria set accuracy is updated
540. If the prediction criteria set accuracy decreases 545 below a
selected number, then a possible prediction criteria set 550 is
formed. The possible prediction criteria set may be formed, for
example, by substituting more stringent condition levels to produce
a more accurate prediction.
[0117] If the detected patient conditions are not consistent 510
with any of the prediction criteria sets in the prediction criteria
library, disordered breathing is not predicted. Within a time
window following the disordered breathing prediction, the system
determines if disordered breathing occurs 555. If disordered
breathing occurs 555, then the system checks to see if the patient
conditions are consistent 560 with any of the possible prediction
criteria sets. If the patient conditions are not consistent 560
with any of the possible prediction criteria sets, a possible
prediction criteria set is formed 565.
[0118] If the patient conditions are consistent 560 with a possible
criteria set, the possible prediction criteria set accuracy is
updated 570. If the possible prediction criteria accuracy increases
beyond a selected number 575, the possible prediction criteria set
is added 580 to the prediction criteria library.
[0119] The block diagram of FIG. 6 illustrates a disordered
breathing therapy system configured in accordance with embodiments
of the invention. According to one embodiment, a disordered
breathing prediction engine 642 is incorporated within a cardiac
rhythm management system 600. The cardiac rhythm management system
may include, for example, a cardiac therapy module 620 including a
pacemaker 622 and an arrhythmia detector/therapy unit 624. The
cardiac therapy module 620 is coupled to a lead system having
electrodes 631 implanted to electrically couple the heart 630 to
the cardiac rhythm management system 600.
[0120] The cardiac rhythm management system 600 includes circuitry
650 for detecting signals from patient-internal sensors such as the
implanted cardiac electrodes 631, and other patient-internal
sensors 680, such as the patient-internal sensors listed in Table
1. The patient-internal sensors 680 may be coupled to the implanted
signal detection circuitry 650 through conducting leads as shown,
or through a wireless connection, for example.
[0121] The cardiac rhythm management system 600 may also include
circuitry 660 for detecting signals from patient-external sensors
690 located outside the patient's body and from patient-reported
input. The patient-external sensors 690 may be coupled to the
detection circuitry 660 through a wireless link. Signals
representing patient-reported data may be input through a
programmer unit 670 that is wirelessly coupled to a telemetry
circuit 675 within the cardiac rhythm management system 600.
[0122] The cardiac therapy module 620 receives cardiac signals from
the implanted cardiac electrodes 631 and analyzes the cardiac
signals to determine an appropriate therapy. The cardiac therapy
may include pacing therapy controlled by the pacemaker 622 to treat
cardiac rhythms that are too slow. The pacemaker 622 controls the
delivery of periodic low energy pacing pulses to one or more of the
heart chambers through cardiac electrodes 631 to ensure that the
periodic contractions of the heart are maintained at a
hemodynamically sufficient rate.
[0123] The cardiac therapy may also include therapy to terminate
tachyarrhythmia, wherein the heart rate is too fast. The arrhythmia
detector/therapy unit 624 detects and treats episodes of
tachyarrhythmia, including tachycardia and/or fibrillation. The
arrhythmia detector/therapy unit 624 recognizes cardiac signals
indicative of tachyarrhythmia and delivers high energy stimulations
to the heart 630 through the implanted electrodes 631 to terminate
the arrhythmia.
[0124] A disordered breathing module 640 incorporated within the
cardiac rhythm management system 600 includes circuitry for
disordered breathing detection 644, as well as the disordered
breathing prediction engine 642. The implanted signal detection
circuitry 650 and patient-reported/patient-external sensor
detection circuitry 660 are coupled to the disordered breathing
module 640. The implanted signal detection circuitry 650 and
patient-reported/patient-external sensor detection circuitry 660
provide signals associated with various patient conditions used for
disordered breathing detection and prediction.
[0125] A prediction of disordered breathing by the disordered
breathing prediction engine 642 may be used to trigger cardiac
pacing therapy delivered by the cardiac therapy module 620 to
mitigate disordered breathing. In one example, the cardiac therapy
module 620 delivers an appropriate electrical stimulation therapy
to the patient's heart 630 through electrodes 631 coupled to the
patient's heart. In one example therapy regime, electrical
stimulation therapy to mitigate disordered breathing may include
pacing at a rate exceeding an intrinsic rate or in excess of the
patient's normal sleep rate. The pacing may involve any or all of
the heart chambers, for example, right and left atria and right and
left ventricles. The pacing may also involve bi-atrial,
bi-ventricular, or multi-site pacing. In one example, the pacing
pulses may be delivered to left and right atria simultaneously, or
according to other timing sequences. In another example, the
simultaneous or otherwise timed pacing pulses may be delivered to
the left and right ventricles of the heart.
[0126] Further, adapting a cardiac electrical therapy to mitigate
disordered breathing may involve adapting a therapy involving
non-excitatory electrical stimulation of one or more heart
chambers, e.g., the left and/or right ventricles, or other cardiac
sites. Non-excitatory electrical stimulation may be delivered
during absolute refractory periods of the cardiac tissue, for
example, to improve cardiac contractility. The non-excitatory
stimulation therapy may be used alone or in combination with
cardiac pacing to provide a comprehensive therapy regimen for
patients with CHF and disordered breathing such as Cheyne-Stokes
respiration.
[0127] FIGS. 7 through 9 illustrate systems that may be used to
implement methods of disordered breathing prediction according to
embodiments of the invention. FIG. 7 illustrates a system for
delivering disordered breathing therapy utilizing the cardiac
rhythm management system incorporating a disordered breathing
prediction engine 710 as discussed in connection with FIG. 6. In
addition to the previously described implanted cardiac electrodes,
the cardiac rhythm management system 710 also includes an
accelerometer mounted within the housing of the cardiac rhythm
management system 710 for sensing patient activity.
[0128] In the embodiment of FIG. 7, the cardiac rhythm management
system 710 further includes a receiver for a proximity to bed
signal that is generated by a proximity to bed beacon 720 located
on or near the patient's bed 730. If the proximity to bed receiver
detects a signal of sufficient strength from the proximity to bed
beacon 720, then the receiver signals that the patient is in
bed.
[0129] The cardiac rhythm management system 710 includes a
transthoracic impedance sensor used to determine patient conditions
including respiration rate, respiration rate variability, tidal
volume, and minute ventilation, for example. In this example, the
disordered breathing prediction engine located within the cardiac
rhythm management system 710 predicts disordered breathing based
primarily on the patient's heart rate and tidal volume. Two
additional signals, the patient's activity level and proximity to
bed, are used to verify the prediction of disordered breathing.
After a prediction of disordered breathing, the cardiac rhythm
management system delivers an appropriate cardiac therapy to
mitigate the disordered breathing.
[0130] Representative graphs of the patient's tidal volume 810,
heart rate 820, and activity level 830 during disordered breathing
prediction are illustrated in FIGS. 8A-8C. In this example, the
patient's tidal volume 810 exhibits a characteristic decrease 812
just before the onset 840 of an episode of disordered breathing
850. Accordingly, a first condition threshold for disordered
breathing prediction is established as a percentage drop in tidal
volume. Additionally, the patient's heart rate 820 exhibits a
decrease 822 that occurs substantially simultaneously with the
decrease in tidal volume 812. A second condition threshold for
disordered breathing detection is established as a percentage drop
in heart rate. If disordered breathing is predicted, therapy may be
delivered to the patient, for example, in accordance with various
cardiac pacing regimens described above.
[0131] Therapy delivered to mitigate disordered breathing may be
adjusted based on an assessment of the therapy. Therapy assessment
may include, for example, assessment of the efficacy of therapy or
assessment of the impact of the therapy on the patient. According
to various embodiments, therapy efficacy may be analyzed and the
therapy regimen may be adapted to provide more effective therapy.
For example, if a delivered therapy does not prevent or otherwise
mitigate the patient's disordered breathing, the therapy may be
modified to include a more aggressive therapy regimen, e.g.,
cardiac pacing at a higher rate.
[0132] According to embodiments of the invention, the therapy may
be adapted to reduce the impact of the therapy on the patient,
e.g., to minimally impact the patient. In adapting a reduced impact
therapy, the system may take into account various conditions for
evaluating the impact of the therapy on the patient. For example,
conditions such as patient comfort, as indicated by patient
feedback, stress on physiological systems involved in the
disordered breathing therapy, interaction with cardiac pacing
algorithms, e.g., bradycardia pacing, cardiac resynchronization
pacing an/or anti-tachycardia pacing, as determined by interactive
effects of the disordered breathing therapy with cardiac pacing,
and/or sleep quality, as measured by one or more sleep quality
indices, may be taken into account to adapt a therapy that reduces
an impact of the therapy on the patient.
[0133] In addition, impact to the patient may involve reduction of
the useful service life of an implantable therapeutic device used
to deliver disordered breathing therapy and/or pacing therapy for
cardiac dysfunction. For example, a level of disordered breathing
therapy may be unacceptably high if the energy requirements of the
therapy result in an excessively reduced device service life. In
this situation, early device removal and replacement produces a
negative impact to the patient. Therefore, cardiac electrical
therapy to mitigate disordered breathing may be adapted based on a
projected reduction in device service life.
[0134] In one example implementation, pacing above a normal sleep
rate may mitigate disordered breathing, but may coincidentally
interrupt the patient's sleep, causing sleep fragmentation and
other undesirable effects. The therapy may be adapted to reduce an
impact of the therapy on the patient. For example, if the delivered
therapy causes an undesirable number of arousals from sleep, the
therapy may be adjusted to a less aggressive therapy regimen, e.g.,
cardiac pacing at a lower rate.
[0135] In another example, the therapy delivered to mitigate
disordered breathing may be adapted to reduce interactions between
the disordered breathing therapy and other therapies delivered to
the patient. For example, some patients may receive one cardiac
electrical stimulation therapy to treat disordered breathing and
other cardiac stimulation therapy to treat cardiac disorders such
as bradycardia or CHF. Interactions may occur between cardiac
electrical therapy to mitigate disordered breathing and the
patient's cardiac pacing regimen, e.g., pacing for bradycardia or
cardiac resynchronization. Such interactions may be factored into
the assessment of the impact disordered breathing therapy on the
overall therapy delivered to the patient.
[0136] In some cases cardiac electrical therapy to mitigate
disordered breathing may enhance cardiac pacing therapy directed to
alleviate a cardiac dysfunction, e.g., bradycardia or CHF. For
example, non-excitatory electrical stimulation of the left
ventricle during an absolute refractory period may be beneficial to
treat CHF and disordered breathing. In other cases, cardiac
electrical therapy for disordered breathing may work at cross
purposes with the patient's cardiac pacing regimen. For example,
pacing therapy delivered to treat disordered breathing may increase
the percentage of heart beats initiated by atrial pacing while
cardiac resynchronization therapy may be optimal when intrinsic
atrial events are allowed to initiate a heart beat. Evaluating the
impact of disordered breathing therapy on the patient preferably
takes into consideration the impact of disordered breathing therapy
on the overall therapeutic goals for the patient, including cardiac
pacing goals and disordered breathing goals.
[0137] FIG. 9 is a flowchart illustrating a method of providing
therapy for disordered breathing according to embodiments of the
invention. According to this method, one or more patient conditions
are detected 910 and a first group of the detected conditions are
used to predict 920 disordered breathing. A therapy is adapted to
mitigate 930 or prevent the disordered breathing based on a second
set of the patient conditions. The adapted therapy is delivered 940
to the patient.
[0138] A representative set of the first and second groups of
patient conditions that may be used for disordered breathing
prediction and therapy assessment, respectively, is provided in
Table 1. As previously discussed, a first group or subset of
conditions is used in connection with disordered breathing
prediction. a second group of conditions, possibly overlapping the
first group, is used for therapy assessment. Several aspects of
therapy may be assessed. In one embodiment, therapy is assessed
based on therapy effectiveness. In another embodiment, therapy is
assessed based on minimal impact to the patient. In yet a further
embodiment, therapy is assessed based on a combination of therapy
effectiveness and minimal impact to the patient.
[0139] As previously discussed, therapy assessment may be
implemented by detecting and analyzing one or more patient
conditions. Conditions used to assess therapy effectiveness may be
different from, or the same as, conditions used to assess the
impact of the therapy on the patient. Table 3 provides a
representative set of conditions that may be used for therapy
assessment.
TABLE-US-00003 TABLE 3 Condition Therapy Impact Therapy Efficacy
Arousal-Based Sleep May be used to assess therapy Fragmentation
Measures impact during sleep. Restful sleep (Patient reported) May
be used to assess therapy impact during sleep. Discomfort (Patient
reported) May be used to assess therapy impact. Pacing algorithm
interaction May be used to assess therapy impact. Remaining useful
life of therapy May be used to assess therapy device impact. Pacing
algorithm interaction May be used to assess therapy impact during
sleep. Disturbed Breathing-Based May be used to analyze/assess
efficacy of Measures therapy to mitigate disordered breathing
episodes. Respiration quality (Patient May be used to
analyze/assess efficacy of reported) therapy to mitigate disordered
breathing episodes. Heart rate variability (HRV) Disordered
breathing causes heart rate variability to decrease. Therapy may be
modified based on changes in HRV Blood pressure Disordered
breathing causes blood pressure increase Sympathetic nerve activity
Changes in sympathetic nerve activity are (SNA) caused by
disordered breathing. Therapy may be adjusted based on the level of
SNA Blood chemistry A number of disordered breathing related
changes may occur in a patient's blood chemistry, including, e.g.,
higher norepinephrine levels, and lower PaCO.sub.2
[0140] It is understood that the patient conditions that may be
used in connection with prediction of disordered breathing and/or
therapy assessment are not limited to the representative sets
listed in Tables 1-3. Further, although illustrative sensing
methods for detecting the patient conditions are provided, it is
understood that the patient conditions may be sensed and detected
using a wide variety of technologies. The embodiments and features
described in the instant disclosure are not limited to the
particular patient conditions or the particular sensing
technologies described herein.
[0141] In one example, conditions related to sleep quality, e.g.,
sleep fragmentation and other arousal-based measures,
patient-reported restful sleep, and discomfort during therapy, may
be used to assess the impact of the therapy on the patient. For
example, if a patient receiving effective disordered breathing
therapy has low sleep fragmentation, reports restful sleep, and
reports no discomfort, the adverse effects of the therapy on the
patient may be relatively low. If sleep fragmentation is relatively
high, or if the patient reports discomfort or feeling tired after
sleeping, these conditions may indicate that therapy is causing
sleep disturbance and/or other undesirable effects. Various methods
and systems for collecting sleep quality data and assessing sleep
quality are described in a commonly owned U.S. Publication No.
2005/0042589, filed concurrently with this application which is
hereby incorporated herein by reference.
[0142] Sleep fragmentation and sleep disruptions may also occur if
disordered breathing therapy is ineffective and disordered
breathing occurs during sleep. Therefore, a therapy impact
assessment based on detected sleep quality and/or patient-reported
restful sleep preferably takes into account an assessment of
therapy effectiveness.
[0143] Some patients may receive cardiac electrical stimulation
therapy for both disordered breathing as well as cardiac disorders
such as bradycardia and/or CHF. Interactions may occur between
cardiac electrical therapy to mitigate disordered breathing and the
patient's cardiac pacing regimen, e.g., pacing for bradycardia or
cardiac resynchronization. Such interactions may be factored into
the assessment of the impact of disordered breathing therapy on the
overall therapy delivered to the patient.
[0144] Interactions between cardiac therapy and disordered
breathing therapy may occur, and detection of the interactions may
be used to adjust therapy. In some cases, cardiac electrical
therapy to mitigate disordered breathing may enhance cardiac pacing
therapy directed to alleviate a cardiac dysfunction, such as
bradycardia or CHF. For example, non-excitatory electrical
stimulation of the left ventricle during an absolute refractory
period may be beneficial to treat both CHF and disordered
breathing.
[0145] In other examples, cardiac electrical therapy for disordered
breathing may work at cross purposes with the patient's cardiac
pacing regimen. A pacing therapy delivered for treatment of
disordered breathing may increase the percentage of heart beats
initiated by atrial pacing. However, a concurrent cardiac
resynchronization therapy may be optimal when intrinsic atrial
events are allowed to initiate a heart beat. In this situation, the
disordered breathing therapy, the cardiac resynchronization
therapy, or both therapies, may be adjusted to reduce undesirable
therapy interactions.
[0146] The effectiveness of disordered breathing therapy may be
assessed by detecting and analyzing episodes of disordered
breathing that occur even though therapy is being delivered to
mitigate disordered breathing. As indicated, a number of conditions
listed in Table 3 may be used in connection with the detection of
disordered breathing. Methods and systems for detecting and
assessing disordered breathing using one or more detected patient
conditions is described in commonly owned U.S. patent application
Ser. No. 10/309,770, filed Dec. 4, 2002, entitled "Detection of
Disordered Breathing."
[0147] The flowchart of FIG. 10 illustrates a method of providing
disordered breathing therapy in accordance with embodiments of the
invention. A first group of patient conditions is detected 1010 and
disordered breathing predicted 1020 based on the first group of
patient conditions. Therapy to mitigate or prevent the disordered
breathing is delivered 1030. A second group of conditions is
detected 1040 and used to assess 1050 the effectiveness of the
therapy. The second group of conditions may include, for example,
conditions used to detect disordered breathing and analyze the
type, frequency, duration, and severity of disordered breathing
episodes. If therapy is ineffective 1060, the therapy regimen may
be adjusted 1070.
[0148] One or more conditions of the second group of conditions are
used to assess 1060 the impact of the therapy on the patient. If
the therapy impacts the patient negatively, for example, by
disrupting sleep or causing discomfort, then therapy parameters may
be adjusted, e.g., to provide a less aggressive therapy
regimen.
[0149] According to various embodiments of the invention,
disordered breathing detection may be used to assess therapy
effectiveness. In one example implementation, episodes of
disordered breathing are detected by analyzing the patient's
respiration. FIG. 11 illustrates a normal respiration pattern as
represented by a transthoracic impedance sensor signal. The
transthoracic impedance increases during respiratory inspiration
and decreases during respiratory expiration. During Non-REM sleep,
a normal respiration pattern includes regular, rhythmic
inspiration--expiration cycles without substantial
interruptions.
[0150] In one embodiment, episodes of disordered breathing may be
detected by monitoring the respiratory waveform output of the
transthoracic impedance sensor. When the tidal volume (TV) of the
patient's respiration, as indicated by the transthoracic impedance
signal, falls below a hypopnea threshold, then a hypopnea event is
declared. For example, a hypopnea event may be declared if the
patient's tidal volume falls below about 50% of the recent average
tidal volume or other baseline tidal volume. When the patient's
tidal volume falls further to an apnea threshold, e.g., about 10%
of the recent average tidal volume, an apnea event is declared.
[0151] In another embodiment, detection of disordered breathing,
including, for example, sleep apnea and hypopnea, involves defining
and examining a number of respiratory cycle intervals. FIG. 12
illustrates respiration intervals used for disordered breathing
detection according to an embodiment of the invention. A
respiration cycle is divided into an inspiration period
corresponding to the patient inhaling, an expiration period,
corresponding to the patient exhaling, and a non-breathing period
occurring between inhaling and exhaling. Respiration intervals are
established using inspiration 1210 and expiration 1220 thresholds.
The inspiration threshold 1210 marks the beginning of an
inspiration period 1230 and is determined by the transthoracic
impedance signal rising above the inspiration threshold 1210. The
inspiration period 1230 ends when the transthoracic impedance
signal is maximum 1240. A maximum transthoracic impedance signal
1240 corresponds to both the end of the inspiration interval 1230
and the beginning of the expiration interval 1250. The expiration
interval 1250 continues until the transthoracic impedance falls
below an expiration threshold 1220. A non-breathing interval 1260
starts from the end of the expiration period 1250 and continues
until the beginning of the next inspiration period 1270.
[0152] Detection of sleep apnea and severe sleep apnea according to
embodiments of the invention is illustrated in FIG. 13. The
patient's respiration signals are monitored and the respiration
cycles are defined according to inspiration 1330, expiration 1350,
and non-breathing 1360 intervals as described in connection with
FIG. 12. A condition of sleep apnea is detected when a
non-breathing period 1360 exceeds a first predetermined interval
1390, denoted the sleep apnea interval. A condition of severe sleep
apnea is detected when the non-breathing period 1360 exceeds a
second predetermined interval 1395, denoted the severe sleep apnea
interval. For example, sleep apnea may be detected when the
non-breathing interval exceeds about 10 seconds, and severe sleep
apnea may be detected when the non-breathing interval exceeds about
20 seconds.
[0153] Hypopnea is a condition of disordered breathing
characterized by abnormally shallow breathing. FIGS. 14A-B are
graphs of tidal volume derived from transthoracic impedance
measurements. The graphs compare the tidal volume of a normal
breathing cycle to the tidal volume of a hypopnea episode. FIG. 14A
illustrates normal respiration tidal volume and rate. As shown in
FIG. 14B, hypopnea involves a period of abnormally shallow
respiration.
[0154] According to an embodiment of the invention, hypopnea is
detected by comparing a patient's respiratory tidal volume to a
hypopnea tidal volume threshold. The tidal volume for each
respiration cycle is derived from transthoracic impedance
measurements acquired in the manner described above. The hypopnea
tidal volume threshold may be established using clinical results
providing a representative tidal volume and duration of hypopnea
events. In one configuration, hypopnea is detected when an average
of the patient's respiratory tidal volume taken over a selected
time interval falls below the hypopnea tidal volume threshold.
Furthermore, various combinations of hypopnea cycles, breath
intervals, and non-breathing intervals may be used to detect
hypopnea, where the non-breathing intervals are determined as
described above.
[0155] FIG. 15 is a flow graph illustrating a method of apnea
and/or hypopnea detection according to embodiments of the
invention. Various parameters are established 1501 before analyzing
the patient's respiration for disordered breathing episodes,
including, for example, inspiration and expiration thresholds,
sleep apnea interval, severe sleep apnea interval, and hypopnea
tidal volume threshold.
[0156] The patient's transthoracic impedance is measured 1505 as
described in more detail above. If the transthoracic impedance
exceeds 1510 the inspiration threshold, the beginning of an
inspiration interval is detected 1515. If the transthoracic
impedance remains below 1510 the inspiration threshold, then the
impedance signal is checked 1505 periodically until inspiration
1515 occurs.
[0157] During the inspiration interval, the patient's transthoracic
impedance is monitored until a maximum value of the transthoracic
impedance is detected 1520. Detection of the maximum value signals
an end of the inspiration period and a beginning of an expiration
period 1535.
[0158] The expiration interval is characterized by decreasing
transthoracic impedance. When the transthoracic impedance falls
below 1540 the expiration threshold, a non-breathing interval is
detected 1555.
[0159] If the transthoracic impedance does not exceed 1560 the
inspiration threshold within a first predetermined interval 1565,
denoted the sleep apnea interval, then a condition of sleep apnea
is detected 1570. Severe sleep apnea is detected 1580 if the
non-breathing period extends beyond a second predetermined interval
1575, denoted the severe sleep apnea interval.
[0160] When the transthoracic impedance exceeds 1560 the
inspiration threshold, the tidal volume from the peak-to-peak
transthoracic impedance is calculated, along with a moving average
of past tidal volumes 1585. The peak-to-peak transthoracic
impedance provides a value proportional to the tidal volume of the
respiration cycle. This value is compared 1590 to a hypopnea tidal
volume threshold. If the peak-to-peak transthoracic impedance is
consistent with 1590 the hypopnea tidal volume threshold for a
predetermined time 1592, then a hypopnea cycle is detected
1595.
[0161] Additional sensors, such as motion sensors and/or posture
sensors, may be used to confirm or verify the detection of a sleep
apnea or hypopnea episode. The additional sensors may be employed
to prevent false or missed detections of sleep apnea/hypopnea due
to posture and/or motion related artifacts.
[0162] Another embodiment of the invention involves classifying
respiration patterns as disordered breathing episodes based on the
breath intervals and/or tidal volumes of one or more respiration
cycles within the respiration patterns. According to this
embodiment, the duration and tidal volumes associated with a
respiration pattern are compared to duration and tidal volume
thresholds. The respiration pattern is detected as a disordered
breathing episode based on the comparison.
[0163] According to principles of the invention, a breath interval
1630 is established for each respiration cycle. A breath interval
represents the interval of time between successive breaths, as
illustrated in FIG. 16. A breath interval 1630 may be defined in a
variety of ways, for example, as the interval of time between
successive maxima 1610, 1620 of the impedance signal waveform.
[0164] Detection of disordered breathing, in accordance with
methods of the invention, involves the establishment of a duration
threshold and a tidal volume threshold. If a breath interval
exceeds the duration threshold, an apnea event is detected.
Detection of sleep apnea, in accordance with this embodiment, is
illustrated in the graph of FIG. 16. Apnea represents a period of
non-breathing. A breath interval 1630 exceeding a duration
threshold 1640, comprises an apnea episode.
[0165] Hypopnea may be detected using the duration threshold and
tidal volume threshold. A hypopnea event represents a period of
shallow breathing. Each respiration cycle in a hypopnea event is
characterized by a tidal volume less than the tidal volume
threshold. Further, the hypopnea event involves a period of shallow
breathing greater than the duration threshold.
[0166] A hypopnea detection approach, in accordance with
embodiments of the invention, is illustrated in FIG. 17. Shallow
breathing is detected when the tidal volume of one or more breaths
is below a tidal volume threshold 1710. If the shallow breathing
continues for an interval greater than a duration threshold 1720,
then the breathing pattern represented by the sequence of shallow
respiration cycles, is classified as a hypopnea event.
[0167] FIGS. 18A and 18B provide charts illustrating classification
of individual disordered breathing events and series of
periodically recurring disordered breathing events, respectively.
As illustrated in FIG. 18A, individual disordered breathing events
may be grouped into apnea, hypopnea, tachypnea and other disordered
breathing events. Apnea events are characterized by an absence of
breathing. Intervals of reduced respiration are classified as
hypopnea events. Tachypnea events include intervals of rapid
respiration characterized by an elevated respiration rate.
[0168] As illustrated in FIG. 18A, apnea and hypopnea events may be
further subdivided as either central events, caused either by
central nervous system dysfunction, or obstructive events, caused
by upper airway obstruction. A tachypnea event may be further
classified as a hyperpnea event, represented by hyperventilation,
i.e., rapid deep breathing. A tachypnea event may alternatively be
classified as rapid shallow breathing, typically of prolonged
duration.
[0169] FIG. 18B illustrates classification of combinations of
periodically recurring disordered breathing events. Periodic
breathing may be classified as obstructive, central or mixed.
Obstructive periodic breathing is characterized by cyclic
respiratory patterns with an obstructive apnea or hypopnea event in
each cycle. In central periodic breathing, the cyclic respiratory
patterns include a central apnea or hypopnea event in each cycle.
Periodic breathing may also be of mixed origin. In this case,
cyclic respiratory patterns have a mixture of obstructive and
central apnea events in each cycle. Cheyne-Stokes is a particular
type of periodic breathing characterized by a gradual waxing and
waning or tidal volume and having a central apnea and hyperpnea
event in each cycle. Other manifestations of periodic breathing are
also possible.
[0170] As illustrated in FIGS. 18C-G, a respiration pattern
detected as a disordered breathing episode may include only an
apnea respiration cycle 1810 (FIG. 18C), only hypopnea respiration
cycles 1850 (FIG. 18F), or a mixture of hypopnea and apnea
respiration cycles 1820 (FIG. 18D), 1830 (FIG. 18E), 1860 (FIG.
18G). A disordered breathing event 1820 may begin with an apnea
respiration cycle and end with one or more hypopnea cycles. In
another pattern, the disordered breathing event 1830 may begin with
hypopnea cycles and end with an apnea cycle. In yet another
pattern, a disordered breathing event 1860 may begin and end with
hypopnea cycles with an apnea cycle in between the hypopnea
cycles.
[0171] FIG. 19 is a flow graph of a method for detecting disordered
breathing by classifying breathing patterns using breath intervals
in conjunction with tidal volume and duration thresholds as
previously described above. In this example, a duration threshold
and a tidal volume threshold are established for determining both
apnea and hypopnea breath intervals. An apnea episode is detected
if the breath interval exceeds the duration threshold. A hypopnea
episode is detected if the tidal volume of successive breaths
remains less than the tidal volume threshold for a period in excess
of the duration threshold. Mixed apnea/hypopnea episodes may also
occur. In these cases, the period of disordered breathing is
characterized by shallow breaths or non-breathing intervals. During
the mixed apnea/hypopnea episodes, the tidal volume of each breath
remains less than the tidal volume threshold for a period exceeding
the duration threshold.
[0172] Transthoracic impedance is sensed and used to determine the
patient's respiration cycles. Each breath 1910 is characterized by
a breath interval, defined by the interval of time between two
impedance signal maxima, and a tidal volume (TV).
[0173] If a breath interval exceeds 1915 the duration threshold,
then the respiration pattern is consistent with an apnea event, and
an apnea event trigger is turned on 1920. If the tidal volume of
the breath interval exceeds 1925 the tidal volume threshold, then
the breathing pattern is characterized by two respiration cycles of
normal volume separated by a non-breathing interval. This pattern
represents a purely apneic disordered breathing event, and apnea is
detected 1930. Because the final breath of the breath interval was
normal, the apnea event trigger is turned off 1932, signaling the
end of the disordered breathing episode. However, if the tidal
volume of the breath interval does not exceed 1925 the tidal volume
threshold, the disordered breathing period is continuing and the
next breath is checked 1910.
[0174] If the breath interval does not exceed 1915 the duration
threshold, then the tidal volume of the breath is checked 1935. If
the tidal volume does not exceed 1935 the tidal volume threshold,
the breathing pattern is consistent with a hypopnea cycle and a
hypopnea event trigger is set on 1940. If the tidal volume exceeds
the tidal volume threshold, then the breath is normal.
[0175] If a period of disordered breathing is in progress,
detection of a normal breath signals the end of the disordered
breathing. If disordered breathing was previously detected 1945,
and if the disordered breathing event duration has not exceeded
1950 the duration threshold, and the current breath is normal, then
no disordered breathing event is detected 1955. If disordered
breathing was previously detected 1945, and if the disordered
breathing event duration has extended for a period of time
exceeding 1950 the duration threshold, and the current breath is
normal, then the disordered breathing trigger is turned off 1960.
In this situation, the duration of the disordered breathing episode
was of sufficient duration to be classified as a disordered
breathing episode. If an apnea event was previously triggered 1965,
then an apnea event is declared 1970. If a hypopnea was previously
triggered 1965, then a hypopnea event is declared 1975.
[0176] FIG. 20 illustrates a block diagram of a system 2000 that
may be used to provide disordered breathing therapy in accordance
with embodiments of the invention. According to various
embodiments, therapy to mitigate disordered breathing may be
triggered by a prediction of disordered breathing. The therapy may
be adapted based on therapy efficacy and/or the impact of the
therapy on the patient.
[0177] In one example implementation, a disordered breathing
therapy control system 2010 is incorporated within a cardiac rhythm
management system 2001 capable of providing therapeutic electrical
stimulation to a patient's heart. The cardiac rhythm management
system 2001 may include, for example, a cardiac therapy module
2020, including a pacemaker 2022, and an arrhythmia
detector/therapy unit 2024. The cardiac rhythm management system
2001 is coupled to a lead system having electrodes 2031
electrically coupling the patient's heart 2030 to the cardiac
rhythm management system 2001.
[0178] The cardiac rhythm management system 2001 may include
circuitry 2050 used to detect signals from patient-internal sensors
such as the implanted cardiac electrodes 2031, and other
patient-internal sensors 2080, including, for example, any of the
patient-internal sensors listed in Table 1. The cardiac electrodes
2031 and the patient-internal sensors 2080 are coupled to a cardiac
signal detector 2052 and a patient-internal sensor signal detector
2053, respectively. The cardiac electrodes 2031 and
patient-internal sensors 2080 may be coupled to the detector system
2050 through conducting leads as shown, or through a wireless
connection, for example.
[0179] The cardiac rhythm management system 2001 may also include
circuitry 2054 for detecting signals from patient-external sensors
2090 positioned outside the patient's body. The patient-external
sensors 2090 may be coupled to the detection circuitry 2054 through
a wireless link. In addition, the patient may input information
relevant to disordered breathing detection or therapy using a
patient input device 2070. Signals representing patient-reported
data may be wirelessly coupled to patient-input detection circuitry
2055.
[0180] The cardiac therapy module 2020 receives cardiac signals
from the implanted cardiac electrodes 2031 and analyzes the cardiac
signals to determine an appropriate cardiac therapy. The cardiac
therapy may include pacing therapy controlled by the pacemaker 2022
to treat cardiac rhythms that are too slow. For example, the
pacemaker 2022 may control the delivery of periodic low energy
pacing pulses to one or more of the heart chambers through the
cardiac electrodes 2031 to ensure that the periodic contractions of
the heart are maintained at a hemodynamically sufficient rate.
[0181] The cardiac therapy may also include therapy to terminate
tachyarrhythmia,
[0182] wherein the heart rate is too fast. The arrhythmia
detector/therapy unit 2024 detects and treats episodes of
tachyarrhythmia, including tachycardia and/or fibrillation. The
arrhythmia detector/therapy unit 2024 recognizes cardiac signal
waveforms indicative of tachyarrhythmia and controls the delivery
of high energy stimulations to the heart 2030 through the implanted
electrodes 2031 to terminate the arrhythmia.
[0183] A disordered breathing control module 2010 incorporated
within the cardiac rhythm management system 2001 includes a
prediction engine 2015, disordered breathing detection circuitry
2016, and a therapy adaptation control module 2011. The signal
detection circuitry 2050 detects conditions relevant to disordered
breathing prediction, detection, and therapy control used by to the
disordered breathing control module 2010.
[0184] A prediction of disordered breathing by the disordered
breathing prediction engine 2015 may be used to trigger cardiac
pacing therapy delivered by the cardiac therapy module 2020 to
mitigate or prevent the disordered breathing. In one illustrative
therapy regimen, pacing to mitigate disordered breathing may
include pacing at a rate exceeding an intrinsic rate. In another
example, the pacing pulses may be delivered at a rate above the
patient's normal sleep rate. The pacing may involve any or all of
the heart chambers, for example, right and left atria and right and
left ventricles. The pacing may also involve bi-atrial,
bi-ventricular, or multi-site pacing. In bi-atrial pacing, the
pacing pulses may be delivered to left and right atria
simultaneously, or according to other timing sequences.
Bi-ventricular pacing may be accomplished by the simultaneous or
otherwise timed application of pacing pulses to the left and right
ventricles of the heart.
[0185] In other embodiments, adapting the cardiac electrical
therapy to mitigate disordered breathing may involve initiating a
particular pacing regimen or switching from one pacing mode to
another pacing mode. In one example, the cardiac pacing regimen may
be switched from a dual-chamber pacing mode to a bi-ventricular or
other resynchronization mode. In other examples, the pacing mode
may be switched to a pacing mode that promotes atrial pacing, or
promotes consistent ventricular pacing. In yet another example, the
cardiac electrical therapy may involve initiating multi-site
electrical stimulation to the heart or changing from one electrical
stimulation site to another. The pacing mode may be switched from
single chamber to multiple chambers, or the reverse. For example, a
bi-ventricular mode may be switched to a left ventricular mode
only. Alternatively, a single chamber mode, e.g., LV or RV, may be
switched to a bi-ventricular mode. Other therapy regimens,
involving, e.g., various pacing modes, pacing sites, or
non-excitatory electrical stimulations, are possible in connection
with providing cardiac electrical therapy for disordered breathing.
The type of cardiac electrical therapy beneficial to a patient is
highly patient specific and may be determined based on the
responses of a particular patient.
[0186] The patient conditions detected by the signal detector
system 2050 are used to adapt disordered breathing therapy with
respect to providing a more effective therapy, or to decrease the
negative impact of the therapy on the patient, or both. A therapy
adaptation control module 2011 coupled to the therapy module
includes components for assessing patient impact 2012 and therapy
efficacy 2013 implemented according to the previously described
methods. The therapy adaptation control module 2011 is coupled to
the therapy control module 2020 and provides control signals to the
therapy module for adapting the therapy.
[0187] FIG. 21 is a flow graph illustrating a method of providing
cardiac pacing therapy for disordered breathing in accordance with
embodiments of the invention. The cardiac pacing therapy is
triggered by a prediction of disordered breathing. In this example,
disordered breathing is predicted based on an air pollution index
obtained from an internet accessible server. Therapy efficacy is
assessed by analyzing respiration patterns detected using a
transthoracic impedance sensor to detect episodes of disordered
breathing. The impact of the therapy on the patient's sleep is
analyzed by determining the number of arousals per hour experienced
by the patient.
[0188] As illustrated in FIG. 21, an air pollution index is
detected 2105, for example, by accessing an internet-connected
website. If the air pollution index exceeds a selected threshold
2110, then disordered breathing is predicted 2115. The air
pollution index threshold may be selected, for example, from data
collected over time from the patient. If disordered breathing is
predicted 2115, therapy to mitigate the disordered breathing, e.g.,
cardiac pacing therapy, is delivered 2120 to the patient. The
pacing may involve, for example, pacing at a predetermined amount
over the intrinsic rate or the current pacing rate. The
predetermined amount may initially be a nominal amount, such as 15
bpm over the intrinsic or the current rate. The pacing rate may be
modified to increase the efficacy of the therapy or to reduce the
impact of the therapy on the patient.
[0189] A transthoracic impedance signal is sensed 2125 and used to
analyze 2130 respiration patterns associated with disordered
breathing. If disordered breathing is detected 2135, then the
delivered therapy may not have been effective 2170. If therapy is
found to be ineffective, the therapy may be adapted 2175.
[0190] In one embodiment, if the frequency, duration, or severity
of the disordered breathing episodes is not mitigated following
therapy delivery, the therapy may be determined to be ineffective
and the pacing rate may be adapted to a higher pacing rate.
Severity of disordered breathing events may be assessed, for
example, as a percentage decrease in tidal volume from the recent
average or baseline tidal volume.
[0191] Disordered breathing time duration thresholds may be defined
to trigger an disordered breathing episode. For example, a
disordered breathing episode may be declared if the patient's tidal
volume falls below an apnea or hypopnea tidal volume threshold for
a period exceeding a disordered breathing duration threshold such
as about 10 seconds. A severe disordered breathing episode may be
declared when the patient's tidal volume falls below an apnea or
hypopnea tidal volume threshold for a period exceeding a severe
disordered breathing duration threshold, e.g., about 60 seconds. If
a severe apnea episode is detected, the severe apnea episode may
trigger pacing at a high rate to arouse the patient and terminate
the apnea. A pacing rate upper limit may be employed to prevent the
pacing rate from becoming too high.
[0192] In one embodiment, if the therapy is determined to be
effective, the pacing rate may be gradually decreased to reduce the
risk of arousal, to avoid unnecessary stress on the heart, and to
prolong battery life.
[0193] If the disordered breathing therapy is determined to be
effective 2135, the impact of the therapy on the patient is
assessed. The patient's sleep quality may be determined by
analyzing patient activity using an accelerometer, for example.
Additional sensors may also be used to provide more sensitive
arousal detection. The accelerometer signal is sensed 2140 and used
to determine 2145 the number of arousals per hour (NH) experienced
by the patient. If the number of arousals per hour is greater 2150
than a threshold value, then the therapy may be arousing the
patient from sleep. In this situation, the impact of the therapy is
not minimal 2165, and the therapy may be adapted 2175. The impact
of the therapy may be further assessed using patient-reported input
2155. If the patient reports that sleep is not restful 2160, then
the therapy regimen may be adapted 2175.
[0194] Although a number of the examples of disordered breathing
therapy provided above involve types of disordered breathing that
generally occur while a person is asleep, disordered breathing may
also occur while a person is awake. While the methods, devices, and
systems of the invention described herein are particularly
well-suited for providing sleep-disordered breathing therapy, the
principles of the invention are also applicable to provided therapy
for disordered breathing episodes that occur while the patient is
awake. Waking disordered breathing is frequently associated with
compromised cardiopulmonary function caused by congestive heart
failure. Examples of the types of disordered breathing that may
occur while a person is awake include, for example, periodic
breathing and Cheyne-Stokes respiration. Cheyne-Stokes respiration
particularly affects patients who have heart problems, such as
congestive heart failure, or nervous disorders, such as those
caused by a stroke.
[0195] The following commonly owned U.S. patents applications, some
of which have been identified above, are hereby incorporated by
reference in their respective entireties: U.S. patent application
Ser. No. 10/309,771 filed Dec. 4, 2002, now U.S. Pat. No.
7,189,204, U.S. patent application Ser. No. 10/309,770 filed Dec.
4, 2002, now U.S. Pat. No. 7,252,640, U.S. patent application Ser.
No. 10/642,998 entitled "Sleep Quality Data Collection and
Evaluation," now U.S. Publication No. 2005/0042589, and
concurrently filed with this patent application, U.S. patent
application Ser. No. 10/643,203 entitled "Adaptive Therapy for
Disordered Breathing," now U.S. Publication No. 2005/0039745 and
filed concurrently with this patent application, U.S. patent
application Ser. No. 10/643,006 entitled "Sleep State
Classification," now U.S. Publication No. 2005/0043652, and filed
concurrently with this patent application, and U.S. patent
application Ser. No. 10/643,016 entitled "Prediction of Disordered
Breathing," now U.S. Pat. No. 7,396,333, and filed concurrently
with this patent application.
[0196] Various modifications and additions can be made to the
preferred embodiments discussed hereinabove without departing from
the scope of the present invention. Accordingly, the scope of the
present invention should not be limited by the particular
embodiments described above, but should be defined only by the
claims set forth below and equivalents thereof.
[0197] Various modifications and additions can be made to the
preferred embodiments discussed hereinabove without departing from
the scope of the present invention. Accordingly, the scope of the
present invention should not be limited by the particular
embodiments described above, but should be defined only by the
claims set forth below and equivalents thereof.
* * * * *