U.S. patent application number 14/740168 was filed with the patent office on 2016-05-12 for method for detecting, diagnosing, and treating cardiovascular disease.
The applicant listed for this patent is Cedars-Sinai Medical Center. Invention is credited to Neal L. Eigler, Brian M. Mann, James S. Whiting.
Application Number | 20160129260 14/740168 |
Document ID | / |
Family ID | 37421116 |
Filed Date | 2016-05-12 |
United States Patent
Application |
20160129260 |
Kind Code |
A1 |
Mann; Brian M. ; et
al. |
May 12, 2016 |
METHOD FOR DETECTING, DIAGNOSING, AND TREATING CARDIOVASCULAR
DISEASE
Abstract
A method of treating cardiovascular disease in a medical patient
is provided. The method includes the steps of generating a sensor
signal indicative of a fluid pressure within the left atrium of the
patient's heart, and delivering an electrical stimulus to a
location in the heart. The electrical stimulus is delivered based
at least in part on the sensor signal. The method also includes the
steps of generating a processor output indicative of a treatment to
a signaling device. The processor output is based at least in part
on the sensor signal. At least two treatment signals are provided
to the medical patient. The treatment signals are distinguishable
from one another by the patient, and are indicative of a
therapeutic treatment. The treatment signals are based at least in
part on the processor output.
Inventors: |
Mann; Brian M.; (Edgartown,
MA) ; Whiting; James S.; (Los Angeles, CA) ;
Eigler; Neal L.; (Malibu, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Cedars-Sinai Medical Center |
Los Angeles |
CA |
US |
|
|
Family ID: |
37421116 |
Appl. No.: |
14/740168 |
Filed: |
June 15, 2015 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11208416 |
Aug 19, 2005 |
9055917 |
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14740168 |
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10697960 |
Oct 29, 2003 |
6970742 |
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11208416 |
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10698031 |
Oct 29, 2003 |
7483743 |
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10697960 |
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10127227 |
Apr 19, 2002 |
7115095 |
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10698031 |
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09956596 |
Sep 19, 2001 |
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10127227 |
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09481084 |
Jan 11, 2000 |
6328699 |
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09956596 |
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60470468 |
May 13, 2003 |
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Current U.S.
Class: |
607/23 |
Current CPC
Class: |
A61B 5/4839 20130101;
A61N 1/37247 20130101; G06F 19/3456 20130101; G16H 40/40 20180101;
G06F 19/3481 20130101; A61N 1/36564 20130101; A61B 5/6882 20130101;
G16H 20/30 20180101; G16H 40/63 20180101; A61B 5/021 20130101; A61B
2560/0209 20130101; A61B 5/02108 20130101; G06F 19/3418 20130101;
A61B 5/0215 20130101; A61N 1/3627 20130101 |
International
Class: |
A61N 1/365 20060101
A61N001/365 |
Claims
1. A method of treating cardiovascular disease in a medical
patient, comprising: generating a sensor signal indicative of a
fluid pressure within a heart; delivering an electrical pulse to
the patient, said delivering based at least in part on the sensor
signal; providing a processor output to a signaling device, wherein
the processor output is indicative of a therapeutic treatment, and
wherein the processor output is based at least in part on the
sensor signal; providing a treatment signal to the medical patient,
wherein the treatment signal is based at least in part on the
processor output.
Description
RELATED APPLICATIONS
[0001] This application is a continuation application of U.S.
application Ser. No. 11/208,416, filed on Aug. 19, 2005. U.S.
application Ser. No. 11/208,416 is a continuation of U.S.
application Ser. No. 10/697,960, filed on Oct. 29, 2003, and U.S.
application Ser. No. 11/208,416 is also a continuation application
of U.S. application Ser. No. 10/698,031, filed on Oct. 29, 2003,
which claims the benefit of Provisional Application No. 60/470,468,
filed May 13, 2003. U.S. application Ser. No. 10/698,031 is a
continuation-in-part of U.S. application Ser. No. 10/127,227, filed
on Apr. 19, 2002, which is a continuation of U.S. application Ser.
No. 09/956,596, filed on Sep. 19, 2001, now abandoned, which is a
continuation of U.S. application Ser. No. 09/481,084, filed on Jan.
11, 2000, now U.S. Pat. No. 6,328,699, all incorporated by
reference herein.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates generally to systems and methods for
detecting, diagnosing and treating cardiovascular disease in a
medical patient.
[0004] 2. Description of the Related Art
[0005] The optimum management of patients with chronic diseases
requires that therapy be adjusted in response to changes in the
patient's condition. Ideally, these changes are measured by daily
patient self-monitoring prior to the development of symptoms.
Self-monitoring and self-administration of therapy forms a closed
therapeutic loop, creating a dynamic management system for
maintaining homeostasis. Such a system can, in the short term,
benefit day-to-day symptoms and quality-of-life, and in the long
term, prevent progressive deterioration and complications.
[0006] In some cases, timely administration of a single dose of a
therapy can prevent serious acute changes in the patient's
condition. One example of such a short-term disease management
strategy is commonly used in patients with asthma. The patient
acutely self-administers an inhaled bronchodilator when daily
readings from a hand-held spirometer or flowmeter exceed a normal
range. This has been effective for preventing or aborting acute
asthmatic attacks that could lead to hospitalization or death
[0007] In another chronic disease, diabetes mellitus, current
self-management strategies impact both the short and long term
sequelae of the illness. Diabetic patients self-monitor blood
glucose levels from one to three times daily and correspondingly
adjust their self-administered injectable insulin or oral
hypoglycemic medications according to their physician's
prescription (known as a "sliding scale"). More "brittle" patients,
usually those with juvenile-onset diabetes, may require more
frequent monitoring (e.g., 4 to 6 times daily), and the readings
may be used to adjust an external insulin pump to more precisely
control glucose homeostasis. These frequent "parameter-driven"
changes in diabetes management prevent hospitalization due to
symptoms caused by under-treatment (e.g., hyperglycemia with
increased hunger, thirst, urination, blurred vision), and
over-treatment (e.g., hypoglycemia with sweating, palpitations, and
weakness). Moreover, these aggressive management strategies have
been shown to prevent or delay the onset of long-term
complications, including blindness, kidney failure, and
cardiovascular disease.
[0008] There are approximately 60 million people in the U.S. with
risk factors for developing chronic cardiovascular diseases,
including high blood pressure, diabetes, coronary artery disease,
valvular heart disease, congenital heart disease, cardiomyopathy,
and other disorders. Another 10 million patients have already
suffered quantifiable structural heart damage but are presently
asymptomatic. Still yet, there are 5 million patients with symptoms
relating to underlying heart damage defining a clinical condition
known as congestive heart failure (CHF). Although survival rates
have improved, the mortality associated with CHF remains worse than
many common cancers. The number of CHF patients is expected to grow
to 10 million within the coming decade as the population ages and
more people with damaged hearts are surviving.
[0009] CHF is a condition in which a patient's heart works less
efficiently than it should, and a condition in which the heart
fails to supply the body sufficiently with the oxygen-rich blood it
requires, either during exercise or at rest. To compensate for this
condition and to maintain blood flow (cardiac output), the body
retains sodium and water such that there is a build-up of fluid
hydrostatic pressure in the pulmonary blood vessels that drain the
lungs. As this hydrostatic pressure overwhelms oncotic pressure and
lymph flow, fluid transudates from the pulmonary veins into the
pulmonary interstitial spaces, and eventually into the alveolar air
spaces. This complication of CHF is called pulmonary edema, which
can cause shortness of breath, hypoxemia, acidosis, respiratory
arrest, and death. Although CHF is a chronic condition, the disease
often requires acute hospital care. Patients are commonly admitted
for acute pulmonary congestion accompanied by serious or severe
shortness of breath. Acute care for congestive heart failure
accounts for the use of more hospital days than any other cardiac
diagnosis, and consumes in excess of 20 billion dollars in the
United States annually.
SUMMARY OF THE INVENTION
[0010] In one embodiment of the present invention, an apparatus for
treating cardiovascular disease in a medical patient is provided.
The apparatus includes a sensor, an implantable cardiac rhythm
management apparatus, an implantable lead, a signal processor, and
a signaling device. The sensor is operable to generate a sensor
signal indicative of a fluid pressure within a left atrium of a
heart. The cardiac rhythm management apparatus includes a housing
and an electrode, where the electrode is operable to deliver an
electrical stimulus to a location in the heart, and where the
electrical stimulus is based at least in part on the sensor signal.
The implantable lead is coupled to the implantable housing and to
the electrode. The signal processor is operable to generate a
processor output indicative of a treatment, where the processor
output is based at least in part on the sensor signal. The
signaling device is operable to generate at least two treatment
signals distinguishable from one another by the patient, where each
signal is indicative of a therapeutic treatment and where the
treatment signals are based at least in part on the processor
output.
[0011] In another embodiment of the invention, an apparatus for
treating cardiovascular disease in a medical patient that includes
a first sensor and a second sensor is provided. The first sensor is
operable to generate a first sensor signal indicative of a fluid
pressure within the heart. The apparatus also includes a cardiac
rhythm management apparatus to deliver at least one electrical
stimulus to a location in the heart, where the electrical stimulus
is based at least in part on the sensor signal. The apparatus also
has at least one implantable lead that is coupled to the cardiac
rhythm management apparatus. The apparatus further includes a
signal processor, operable to generate a processor output
indicative of a treatment, wherein the processor output is based at
least in part on the first sensor signal. The apparatus also has a
signaling device, operable to generate at least two treatment
signals distinguishable from one another by the patient, each
signal indicative of a therapeutic treatment, and where the
treatment signals are based at least in part on the processor
output. The apparatus, in one embodiment, may include an electrode
as part of the cardiac rhythm management apparatus.
[0012] In a further embodiment of the invention, an apparatus for
treating cardiovascular disease is provided. The apparatus includes
an implantable sensor module, operable to generate a sensor signal
indicative of a fluid pressure within the left atrium of a heart.
The apparatus also has an implantable flexible lead connecting the
sensor module to an implantable housing, where the housing has a
telemetry apparatus configured to communicate the sensor signal
through the patient's skin. The apparatus also includes an external
telemetry device configured to communicate with the implantable
apparatus. The apparatus further includes a signal processing
apparatus operable to generate a signal indicative of an
appropriate therapeutic treatment based at least in part on the
sensor signal and a patient signaling device operable to generate
at least two treatment signals distinguishable from one another by
the patient, each treatment signal indicative of a therapeutic
treatment.
[0013] In yet another embodiment, an apparatus for treating
cardiovascular disease that includes a sensor, a cardiac rhythm
management apparatus, a telemetry apparatus, at least one
implantable lead, a signal processor, and a signaling device is
provided. The sensor is operable to generate a pressure signal
indicative of a fluid pressure within a left atrium of a heart. The
cardiac rhythm management apparatus, the cardiac rhythm management
apparatus includes an electrode which is operable to deliver at
least one electrical stimulus to a location in the heart. The
electrical stimulus is based at least in part on the pressure
signal. The telemetry apparatus is operable to transmit the
pressure signal to a location outside of the patient. The
implantable lead is coupled to the electrode. The signal processor
is operable to generate a processor output indicative of a
therapeutic treatment, where the processor output is based at least
in part on the pressure signal. The signaling device is operable to
communicate the processor output to the medical patient.
[0014] In one embodiment of the invention, an apparatus for
treating cardiovascular disease in a medical patient is provided.
The apparatus includes a sensor operable to generate a pressure
signal indicative of one or more pressures, or pressure parameters
within the heart, a telemetry apparatus operable to communicate the
pressure signal to a location outside of the medical patient, and a
signal processor operable to generate a treatment signal indicative
of a therapeutic treatment. The treatment signal is based at least
in part on the pressure signal. The apparatus also includes a
signaling device operable to communicate the treatment signal to a
user.
[0015] In yet another embodiment of the invention, an apparatus for
treating or preventing cardiovascular disease is provided. The
apparatus includes a sensing means for generating a signal
indicative of one or more cardiac pressures, a means to deliver an
electrical stimulus to the heart, a signal processor for generating
a treatment signal indicative of a treatment, where the treatment
signal is based at least in part on the pressure signal, at least
one implantable lead coupled to the means to deliver an electrical
stimulus, and a signaling means for communicating the treatment
signal a user. In one embodiment, the sensing means includes a
pressure transducer. In one embodiment, the means to deliver an
electrical stimulus includes a pacemaker. In one embodiment, the
means to deliver an electrical stimulus includes a defibrillator.
In one embodiment, the signaling means includes a personal digital
assistant.
[0016] In another embodiment of the invention, an apparatus for
treating cardiovascular disease in a medical patient is provided.
The apparatus includes a sensor to generate a sensor signal
indicative of a fluid pressure within the left atrium and a cardiac
rhythm management apparatus to deliver an electrical stimulus to
the patient. The apparatus also includes a signal processor to
generate a processor output indicative of a treatment, where the
processor output is based at least in part on the sensor signal,
and a signaling device to generate at least two treatment signals
distinguishable from one another by the patient. Each signal
indicates a therapeutic treatment and is based at least in part on
the processor output.
[0017] In one embodiment of the present invention, a method of
treating cardiovascular disease in a medical patient is provided.
The method includes the steps of generating a sensor signal
indicative of a fluid pressure within a left atrium of a heart,
delivering an electrical stimulus to the heart, generating a
processor output indicative of a treatment to a signaling device,
and providing at least two treatment signals to the medical
patient. The electrical stimulus is based at least in part on the
sensor signal. The processor output is based at least in part on
the sensor signal. Each treatment signal is distinguishable from
one another by the patient, and is indicative of a therapeutic
treatment. At least one signal is based at least in part on the
processor output. In one embodiment, the step of delivering an
electrical stimulus includes using a pacemaker or a
defibrillator.
[0018] In another embodiment, a method of treating cardiovascular
disease is provided. The method includes generating a sensor signal
indicative of a fluid pressure within the heart and delivering an
electrical stimulus to the patient, such as, for example, to a
location in the heart. The method further includes providing a
processor output indicative of a treatment, and providing at least
two treatment signals to the medical patient. The electrical
stimulus is based at least in part on the sensor signal. The
processor output is based at least in part on the sensor signal.
The treatment signals are distinguishable from one another by the
patient and are based at least in part on the processor output.
[0019] In a further embodiment of the current invention, a method
of treating cardiovascular disease that includes a telemetry device
is provided. The method includes the steps of generating a sensor
signal indicative of a fluid pressure within a left atrium of a
heart, and transmitting the sensor signal using an internal
telemetry apparatus to an external telemetry device. The method
further includes providing the sensor signal from the external
telemetry device to a signal processor, processing the sensor
signal to generate a treatment signal, and communicating the
treatment signal to a user by providing at least two signals to the
user.
[0020] In yet another embodiment of the invention, a method of
determining fluid pressure within the left atrium of a medical
patient's heart is provided. The method includes the steps of
obtaining a sensor signal from the one or more implanted sensors in
a medical patient by telemetry through the patient's skin,
obtaining the atmospheric pressure, and determining an adjusted
pressure signal. The adjusted pressure signal is based at least in
part upon the sensor signal and the obtained atmospheric pressure
and substantially indicates the fluid pressure within the left
atrium of the heart relative to the atmospheric pressure.
[0021] In another embodiment of the present invention, a method of
treating or preventing cardiovascular disease in a medical patient
using at least two sensors is provided. The method includes
generating a first sensor signal indicative of a cardiac fluid
pressure within the patient, and generating a second signal
indicative of a physiological parameter. The method further
includes delivering an electrical stimulus to the patient, where
the electrical stimulus is based at least in part on the first
sensor signal. The method also includes generating a processor
output indicative of a treatment to a signaling device, where the
processor output is based at least in part on the first sensor
signal, and providing at least two treatment signals to the
patient. The treatment signals are distinguishable from one another
by the patient, are indicative of different therapeutic treatments,
and are based at least in part on the processor output.
[0022] In another embodiment of the present invention, a method of
treating cardiovascular disease using electrical pulses is
provided. The method includes generating a sensor signal indicative
of a fluid pressure within a heart and delivering at least one
electrical pulse to the patient, where the pulse delivery is based
at least in part on the sensor signal. The method also includes
providing a processor output to a signaling device, where the
processor output is indicative of a therapeutic treatment, and
where the processor output is based at least in part on the sensor
signal. The method further includes providing a treatment signal to
the medical patient, where the treatment signal is based at least
in part on the processor output.
[0023] In one embodiment of the invention, a method for treating
cardiovascular disease is provided. The method includes generating
a pressure signal indicative of a fluid pressure within a heart and
controlling the delivery of an electrical pulse from a pacemaker to
the heart. The controlling step is based at least in part on the
pressure signal. The method further includes communicating the
pressure signal to a patient signaling apparatus located at least
partially external to the medical patient. The method also includes
processing the pressure signal with the patient signaling apparatus
to determine a processor output indicative of a therapeutic
treatment, the therapeutic treatment based at least in part on the
fluid pressure within the heart, and signaling the patient with the
processor output.
[0024] In yet another embodiment of the invention, a method for
treating cardiovascular disease in a medical patient that includes
the following steps is provided: generating a pressure signal
indicative of a fluid pressure within a heart, communicating the
pressure signal to location outside of the medical patient,
generating a processor output indicative of a therapeutic
treatment, where the processor output is based at least in part on
the pressure signal, and communicating the processor output to the
medical patient.
[0025] In an alternative embodiment of the present invention, a
method for treating cardiovascular disease in a medical patient
includes generating a sensor signal indicative of a fluid pressure
within the left atrium, communicating the sensor signal to an
external telemetry apparatus, and generating a processor output
indicative of an appropriate therapeutic treatment based at least
in part on the sensor signal. The method further includes signaling
a patient with a patient signaling device. The signaling device is
operable to generate at least two treatment signals distinguishable
from one another by the patient, each treatment signal indicative
of a therapeutic treatment, wherein each treatment signal is based
at least in part on the processor output.
[0026] In several embodiments of the current invention, the
apparatus and/or method for treating cardiovascular disease
includes a cardiac rhythm management apparatus. In one embodiment,
the cardiac rhythm management apparatus includes a pacemaker. In
another embodiment, the cardiac rhythm management apparatus
includes a defibrillator. In one embodiment, the cardiac rhythm
management apparatus is controlled at least in part by one or more
sensor signals, including, but not limited to, one or more pressure
signals.
[0027] In one embodiment, the apparatus and/or method for treating
cardiovascular disease includes an external patient advisory
module. In one embodiment, the external patient advisory module
includes an external telemetry device, a signal processor, and a
signaling device. In one embodiment, the external patient advisory
module includes a barometer configured to sense atmospheric
pressure.
[0028] In several embodiments of the current invention, the
apparatus and/or method for treating cardiovascular disease
includes one or more sensors. In one embodiment, the sensor
includes a pressure transducer. In another embodiment, the sensor
is in pressure communication with the left atrium. In one
embodiment, the sensor is located in the atrial septum or the left
atrium. In one embodiment, the sensor is placed in one or more of
the following locations: a right atrial appendage, a left atrial
appendage, a pulmonary artery, a pulmonary vein, a pulmonary
capillary wedge position, a right ventricle, a left ventricle, a
right atrium, an intrathoracic space, and a central vein. In one
embodiment, the sensor includes a low compliance titanium foil. In
one embodiment, the sensor includes at least one silicon strain
gauge.
[0029] In several embodiments of the current invention, the
apparatus and/or method for treating cardiovascular disease
includes one or more sensor signals. In one embodiment, the sensor
signal includes at least one pressure signal. In one embodiment,
the pressure signal includes a central venous blood pressure, a
peripheral arterial blood pressure and/or a left atrial pressure.
In another embodiment, the pressure signal includes a parameter of
a left atrial pressure. In one embodiment, the parameter is
selected from the group including, but not limited to one or more
of the following: mean left atrial pressure, temporally filtered
left atrial pressure, heart rate, respiratory variation of left
atrial pressure, and respiration rate. In another embodiment, the
parameter is determined based upon at least one wave selected from
the group including, but not limited to one or more of the
following: an a wave, a v wave, and a c wave. In yet another
embodiment, the parameter is determined based upon a parameter
signal selected from the group including, but not limited to one or
more of the following: a wave amplitude, a waveform rate of ascent,
a waveform rate of descent, timing of a wave feature with respect
to a cardiac cycle, timing of a wave feature with respect to
another wave feature, time difference between an a wave and a c
wave, time difference between an a wave and a v wave, and time
difference between a v wave and a c wave. In one embodiment, the
parameter is determined based upon at least one descent selected
from the group including, but not limited to one or more of the
following: an x descent, an x' descent, and a y descent. In another
embodiment, the parameter is determined based upon a parameter
signal selected from the group including, but not limited to one or
more of the following: a descent amplitude, a descent rate of
ascent, a descent rate of descent, timing of a descent feature with
respect to a cardiac cycle, timing of a descent feature with
respect to another wave feature, time difference between an x
descent and an x' descent, time difference between an x descent and
a y descent, and time difference between an x' descent and a y
descent. In one embodiment, the parameter is independent of ambient
atmospheric pressure.
[0030] In one embodiment, the sensor signal is measured during an
interval. In another embodiment, the sensor signal is sampled in
response to an event, including but not limited to a detected
event, a symptom, and/or an instruction.
[0031] In one embodiment, the apparatus and/or method for treating
cardiovascular disease further includes a sensor module. The sensor
module includes at least one sensor. In one embodiment, the sensor
module has a cylindrical shape. In one embodiment, the sensor
module has a length of about 8 mm, and a diameter of about 3 mm. In
one embodiment, the sensor module has a length in a range between
about 5 and 15 mm, and a diameter in a range between about 1 and 5
mm. In one embodiment, the sensor module is connected to at least
one implantable lead. In another embodiment, the sensor module is
coupled to an implantable housing with an additional lead. In one
embodiment, the sensor is connected to the implantable housing. In
yet another embodiment, the sensor module further includes
electronics. In one embodiment, the electronics comprise an
application-specific integrated circuit (ASIC) and/or an
analog-to-digital converter. In a further embodiment, the
electronics include circuitry for communicating a digital
signal.
[0032] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease further includes a
housing that is a flat oval shape. In one embodiment, the housing
includes a first dimension and a second dimension, where the first
dimension is about 30 mm and the second dimension is about 20 mm.
In one embodiment, the housing is implanted near a shoulder in the
medical patient or in an abdominal site. In another embodiment, the
housing further includes an antenna or coil. In one embodiment, the
housing further includes a power source.
[0033] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease has a signaling device
that is at least partially located in the housing. In another
embodiment, the apparatus further includes a telemetry apparatus.
In one embodiment, the telemetry apparatus is at least partially
located within the housing. In one embodiment, the housing further
includes a data memory.
[0034] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease has a signal processor
that is located in an external apparatus outside of the patient's
body. In one embodiment, the external apparatus includes an
external telemetry apparatus. In one embodiment, the external
telemetry apparatus includes, but is not limited to, a personal
digital assistant, a computer, a radio frequency telemetry hardware
module, and a coil antenna. In one embodiment, the telemetry
apparatus is operable to communicate by reflected impedance of
radio frequency energy. In a further embodiment, the telemetry
apparatus is operable to communicate by frequency or amplitude
shifting of radio frequency energy.
[0035] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes an external
power source. In one embodiment, the power source provides power
through radio frequency coupling. In one embodiment, the radio
frequency includes, but is not limited to, frequencies of about 125
kHz, about 8192 Hz, about 10.9 kHz, and about 30 kHz.
[0036] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes a signal
processor. The signal processor can be located inside the patient,
on the patient, completely outside the patient, or partially in or
on the patient. In one embodiment, the signal processor includes a
personal digital assistant.
[0037] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes at least one
implantable lead. In one embodiment, two leads are provided. In
another embodiment, three leads are provided. In another
embodiment, more than three leads are provided. In one embodiment,
the lead includes a pacemaker lead. In one embodiment, the lead
includes a defibrillator lead. In one embodiment, the lead carries
a lead signal. In one embodiment, the lead signal includes, but is
not limited to, an electrical signal, a hydraulic signal, an
optical signal, and/or an ultrasonic signal, or some combination
thereof. In one embodiment, the lead communicates the sensor signal
to the implantable housing. In one embodiment, the sensor signal
and the electrical stimulus are provided by the implantable lead.
In another embodiment, the implantable lead provides one or more
power pulses between the implantable housing and the sensor. In one
embodiment, the implantable lead provides a data signal between the
implantable housing and the sensor. In one embodiment, the data
signal includes, but is not limited to one or more of the
following: a pressure signal, a non-pressure sensing signal, a
pacing signal and a programming signal.
[0038] In one embodiment, the implantable flexible lead is
upgradable. In one embodiment, the implantable flexible lead is
configured to operate in a plurality of configurations. In one
embodiment, the lead is configured to operate in a telemetry
configuration. In another embodiment, the lead is configured to
operate in a telemetry configuration and a cardiac management
configuration. In a further embodiment, the implantable flexible
lead is configured to operate in a telemetry configuration and a
therapy configuration. In one embodiment, the implantable flexible
lead includes electronics that automatically senses the appropriate
configuration.
[0039] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes a signaling
device. In one embodiment, the signaling device includes a personal
digital assistant. In one embodiment, the signaling device
includes, but is not limited to an electrical buzzer, an alarm,
and/or a telephone. In one embodiment, the signaling device
provides an audible signal. In one embodiment, the signaling device
provides a visible signal.
[0040] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes processor
output. In one embodiment, the processor output comprises a signal
output from the signal processor. In one embodiment, the processor
output comprises a signal output to the signaling device. In one
embodiment, the processor output includes, but is not limited to
text, numerical, and/or graphics display. In one embodiment, the
processor output includes, but is not limited to codes and
data.
[0041] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes at least one
anchor. In one embodiment, the sensor package, or module, has
anchoring mechanisms configured to anchor the sensor package within
the atrial septum of a patient's heart. In another embodiment, one
or more anchors are used to position or hold one or more of the
components described herein to a site within the patient.
[0042] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease further includes an
automated therapy device. In one embodiment, the automated therapy
device includes, but is not limited to, a dynamic prescription, a
drug delivery unit, and/or a cardiac rhythm management apparatus.
In one embodiment, the automated therapy device controls the AV
interval of a dual chamber pacemaker. In one embodiment, the
automated therapy device is at least partially controlled based
upon parameters indicative of congestive heart failure. In another
embodiment, the automated therapy device is at least partially
controlled based upon parameters indicative of atrial
fibrillation.
[0043] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes a signal
processor that generates the processor output based in part on a
physician's dynamic prescription. In one embodiment, the dynamic
prescription includes at least two treatment instructions
corresponding to at least two physiological conditions. In one
embodiment, a physician workstation is provided that is configured
to receive and store the dynamic prescription. In another
embodiment, an interface for communicating the stored dynamic
prescription from the physician workstation to the signal processor
is provided.
[0044] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes the generation
of at least one treatment signal. In one embodiment, the treatment
signal includes a patient instruction. In one embodiment, the
treatment signal is a numerical designation. In one embodiment, two
treatment signals are provided. In one embodiment, both treatment
signals are numerical designations. In one embodiment, the
numerical designation is indicative of a pressure measurement. In
one embodiment, the treatment signal is based at least in part on
two or more physician instructions. In one embodiment, the
treatment signal is provided to a user. In one embodiment, the user
is a medical practitioner. In one embodiment the, the user is a
patient. In one embodiment, the treatment signal is provided
substantially simultaneously two or more users.
[0045] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease is configured to treat
or prevent congestive heart failure.
[0046] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes one or more
additional sensors in addition to a first sensor. In one
embodiment, a range of about three sensors to about twenty sensors
is provided. In one embodiment, more than twenty sensors are
provided. In one embodiment, a first sensor and a second sensor is
provided. In one embodiment, the first sensor and the second sensor
are located within a sensor module. In one embodiment, the first
sensor is implanted within the patient and the second sensor is
located externally to the patient, either on the patient or
completely independent of the patient. In one embodiment, the
second sensor measures a physical dimension. The physical dimension
includes, but is not limited to, a left atrial dimension, a left
atrial cross-sectional area, a left atrial volume, a left
ventricular dimension, a left ventricular cross-sectional area, and
a left ventricular volume. In one embodiment, at least one of the
sensors measures a parameter that includes, but is not limited to,
one or more of the following: electrical activity of the heart, a
temperature, an atrial septum position, a velocity of a cardiac
structure, an acceleration of a cardiac structure, an electrical
resistance, a thoracic electrical impedance, a respiratory tidal
volume, a respiratory rate, a respiratory minute volume, a total
body weight, oxygen saturation, oxygen partial pressure, oxygen
partial pressure in a left chamber of a heart, oxygen partial
pressure in a right chamber of a heart, and cardiac output. In one
embodiment, a single sensor measure two or more parameters and is
multi-functional. In one embodiment, a second sensor includes an
automated arterial pressure cuff or a weight scale.
[0047] The embodiments summarized above and described in greater
detail below are useful for the treatment of cardiovascular
disease, including congestive heart failure (CHF). CHF is an
important example of a medical ailment currently not treated with
timely, parameter-driven adjustments of therapy, but one that the
inventors believe could potentially benefit greatly from such a
strategy. Patients with chronic CHF are typically placed on fixed
doses of four or five drugs to manage the disease. The drug regimen
commonly includes but is not limited to diuretics, vasodilators
such as ACE inhibitors or A2 receptor inhibitors, beta-blockers
such as Carvedilol, neurohormonal agents such as spironolactone,
and inotropic agents usually in the form of cardiac glycosides such
as, for example, Digoxin.
[0048] The inventors believe that it would be far more cost
effective, and much better for the patient's health, if chronic CHF
could be managed and controlled by the routine administration of
appropriate outpatient oral drug therapy rather than by hospital
treatment upon the manifestation of acute symptoms. As with all
drugs, these agents are to be taken in doses sufficient to ensure
their effectiveness. Problematically, however, over-treatment can
lead to bradycardia, hypotension, renal impairment, hyponatremia,
hypokalemia, worsening CHF, impaired mental functioning, and other
adverse conditions. Adding to the challenge of maintaining proper
drug dosage is the fact that the optimal dosage will depend on
diet, particularly salt and fluid intake, level of exertion, and
other variable factors. Adding further to the problem of managing
this condition is the fact that patients frequently miss scheduled
doses by forgetting to take pills on time, running out of
medications, or deciding to stop medications without consulting
their physician. It is important, therefore, that the patient's
condition be monitored regularly and thoroughly, so that optimal or
near optimal drug therapy can be maintained. Easily obtained
measures of a patient's condition are known, such as weight,
peripheral blood pressure, subcutaneous edema, temperature, and
subjective measures such as fatigue and shortness of breath.
Unfortunately, these measures either do not correlate well enough
with specific physiological states to serve as a controlling
parameter for therapy, or do correlate but change too late for
adjustment of oral medications to be effective. Measures that do
change specifically, sensitively, and early in response to changes
in the patient's condition are known in the art of heart failure
management, but monitoring these measures is problematic in that
such monitoring typically involves inserting a catheter into the
heart or central blood vessels, therefore requiring frequent visits
with a caregiver, and resulting in discomfort, inconvenience,
expense, and repeated risks.
[0049] The inventors believe that it would be advantageous,
therefore, if methods and apparatus could be devised by which an
outpatient's cardiovascular status in general, and congestive heart
failure in particular, could be monitored routinely or
continuously, without performing an invasive procedure each time,
with attendance by a caregiver only when actually required. The
inventors believe that it would be further advantageous if such
methods and apparatus included the ability to communicate
diagnostic and treatment information promptly to the patient
himself. Such feedback would allow the patient to continue or
modify his medications, as prescribed by his physician or licensed
caregiver, such that optimal therapeutic doses are achieved,
generally without the direct intervention of his physician.
[0050] For some classes of drugs (e.g., beta blockers, digoxin,
calcium antagonists, amiodorone, etc.), the optimal dose for
treating heart failure may be associated with, or exaggerate,
episodes of excessively lowered resting heart rate (bradycardia) or
an inability to adequately increase heart rate in response the
body's demand for augmented blood flow (cardiac output), such as
occurs with exercise or stress. The latter condition is known as
chronotropic incompetence. Inappropriately low heart rate causes
fatigue, poor exercise tolerance, and in the worst cases,
deteriorating kidney function, low blood pressure and shock. The
risk of these potentially serious complications limits the dose of
these beneficial drugs that can be safely prescribed.
[0051] It would be additionally advantageous, therefore, if the
methods and apparatus for monitoring a patient's cardiovascular
status in general, and congestive heart failure in particular, and
notifying the patient to continue or modify his medications, could
also provide electronic pacemaker stimulation of the heart as
needed to prevent bradycardia or chronotropic incompetence as a
side effect of these drugs.
[0052] Several embodiments of the present invention provides these
advantages, along with others that will be further understood and
appreciated by reference to the written disclosure, figures, and
claims included herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0053] The structure and operation of the invention will be better
understood with the following detailed description of embodiments
of the invention, along with the accompanying illustrations, in
which:
[0054] FIG. 1 depicts apparatus suitable for practicing at least
one embodiment of the invention.
[0055] FIG. 2 depicts an implantable apparatus suitable for
practicing another embodiment of the invention.
[0056] FIG. 3 is a schematic of one embodiment of the electronics
located within the implantable housing of the implantable apparatus
illustrated in FIG. 2.
[0057] FIG. 4 is a system for treating cardiovascular disease.
[0058] FIG. 5 is a block diagram of an external patient
advisor/telemetry module for use in one embodiment of the present
invention.
[0059] FIGS. 6A-6C provide a list of examples by which signals may
be interpreted to facilitate diagnosis, prevention and treatment of
cardiovascular disease.
[0060] FIG. 7 shows a table of cardiac and non-cardiac diagnostic
states derivable from measurements at the intra-atrial septum.
[0061] FIG. 8 shows the flexible lead of FIG. 13. The sheath has
been withdrawn to deploy the proximal distal anchors on the right
and left atrial sides of the atrial septum, and a pressure sensing
transducer is in fluid contact with the patient's left atrium.
[0062] FIG. 9 depicts a method for anchoring a flexible electrical
lead within the patient's heart.
[0063] FIG. 10 is a schematic sectional view of a patient's heart
illustrating an atrial septal puncture for implanting one
embodiment of the current invention.
[0064] FIG. 11 shows another method for anchoring a lead within the
heart, which includes a helical screw for advancement into the
patient's atrial septum.
[0065] FIG. 12 shows the apparatus depicted in FIG. 11, with a
pressure sensing transducer in place in the patient's left
atrium.
[0066] FIG. 13 is a schematic sectional view of a patient's heart
showing a part of an embodiment of the invention positioned
therein.
[0067] FIG. 14 shows the flexible lead of FIG. 15 and FIG. 16, with
a pressure sensing transducer in place inside the patient's left
atrium.
[0068] FIG. 15 depicts a flexible lead including deployable anchors
carried inside a removable sheath and placed through the atrial
septum.
[0069] FIG. 16 shows the flexible lead of FIG. 15 with the sheath
withdrawn to deploy the anchors on opposite sides of the atrial
septum.
[0070] FIG. 17 shows the correlation between the pulmonary
capillary wedge pressure (PCW) referenced to atmospheric pressure
(abscissa) and the differential pressure between the right atrium
and PCW (PCW-RA).
[0071] FIG. 18 illustrates typical normal pressure tracings.
[0072] FIG. 19 provides a table of normal hemodynamic values.
[0073] FIG. 20 shows a combination of one embodiment of the present
invention with an implantable cardiac pacemaker, in which the
sensor is a left atrial pressure sensor implanted in the
intra-atrial septum, and the pacemaker leads are entirely separate
from the pressure sensor lead.
[0074] FIG. 21 shows the relationships between the
electrocardiogram and the left atrial pressure tracing.
[0075] FIG. 22 is a sensor package or module in accordance with one
embodiment of the present invention.
[0076] FIG. 23 is another sensor package or module in accordance
with another embodiment of the present invention.
[0077] FIG. 24 is a pulse timing diagram showing one embodiment for
sensing one or more physiological parameters and performing cardiac
pacing using a two-conductor digital sensor/pacemaker lead.
[0078] FIG. 25 is a schematic showing one embodiment of circuitry
that provides both pacing and physiological monitoring over a
two-conductor pacemaker lead.
[0079] FIGS. 26A-D are schematics showing circuitry within a sensor
module in accordance with another embodiment of the present
invention.
[0080] FIG. 27 is a schematic diagram depicting digital circuitry
suitable for use in one embodiment of the invention.
[0081] FIG. 28 is an implantable housing in accordance with one
"Stand-Alone" embodiment of the invention.
[0082] FIG. 29 is an implantable housing in accordance with one
"CRM Combination" embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0083] In one embodiment of the present invention an apparatus for
treating cardiovascular disease in a medical patient is provided.
The apparatus includes a sensor, an implantable housing, at least
one implantable lead, a signal processor, and a signaling device.
In one embodiment, the apparatus is a physiologically optimized
dosimeter (POD.TM.), such as the HEARTPOD.TM. device developed by
the Applicant. Cardiovascular disease, as used herein, shall be
given its ordinary meaning, and shall also include high blood
pressure, diabetes, coronary artery disease, valvular heart
disease, congenital heart disease, arrthymia, cardiomyopathy, and
CHF.
[0084] In one embodiment of the present invention, a method of
treating cardiovascular disease in a medical patient is provided.
The method includes the steps of generating a sensor signal
indicative of a fluid pressure within a left atrium of a heart,
delivering an electrical stimulus to the heart, generating a
processor output indicative of a treatment to a signaling device,
and providing at least two treatment signals to the medical
patient. The electrical stimulus is based at least in part on the
sensor signal. The processor output is based at least in part on
the sensor signal. Each treatment signal is distinguishable from
one another by the patient, and is indicative of a therapeutic
treatment. At least one signal is based at least in part on the
processor output. In one embodiment, the step of delivering an
electrical stimulus includes using a pacemaker or a
defibrillator.
[0085] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes one or more
sensors. In one embodiment, the sensor is designed to generate a
sensor signal that is indicative of a fluid pressure within the
left atrium of the patient's heart. As described herein, fluid
pressure within the left atrium of a patient's heart is an
excellent indicator for quantifying the severity of congestive
heart failure, and for assessing the affectivity of drug therapy
for treating congestive heart failure. A measurement of the fluid
pressure within the left atrium of a patient's heart can be used
for other clinical purposes as well, as described in greater detail
below.
[0086] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes one more
housing units. In one embodiment, the implantable housing of the
apparatus includes a cardiac rhythm management (CRM) apparatus,
such as, for example, a pacemaker, or a defibrillator. The
implantable housing generally includes various subassemblies for
control, operation, processing, and communication. However, in some
embodiments, any one or more of control, operation, processing, and
communication may be performed by an assembly, or module that is
not included with the implantable housing. In one embodiment, when
implanted in the patient, the implantable housing contains a coil
antenna and electronics to provide reflected impedance
communications with an external device. However, the implantable
housing may be subsequently accessed, and the coil antenna may be
removed and replaced with a CRM. The implantable housing and
electronics may include an interface that permits such
interchangeability of components within the implantable housing
without requiring explanation of the remaining components of the
congestive heart failure treatment apparatus. These and additional
embodiments of the implantable housing as well as the apparatus are
provided in greater detail below.
[0087] In one embodiment, the lead couples the sensor to the
implantable housing, and provides an electrical conduit for the
transmission of the sensor signal from the sensor to the housing.
In other embodiments, however, as described in greater detail
below, the lead provides an electrical stimulus, such as, for
example, an electrical pulse, to a location in the heart, as
determined by the CRM apparatus. In some embodiments, the
electrical stimulus and the sensor signal are transmitted through
the same lead, and in other embodiments, more than one lead is
provided. In yet another embodiment, energy or power is transmitted
from the implantable housing through the lead to a distal module
that may contain a CRM, sensor, and electronics necessary to
control the congestive heart treatment apparatus. These and other
embodiments are described in greater detail below.
[0088] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes one or more
signal processors. In one embodiment, the signal processor
determines a processor output that is indicative of an appropriate
therapeutic treatment in response to the pressure-indicative signal
provided by the sensor. The processor output is provided to a
signaling device, which provides an appropriate treatment signal to
the medical patient. The term "processor output" as used herein
shall be given its ordinary meaning and shall also mean output from
a signal processor and/or input to a signaling device, and shall
include, but not be limited to, signals, including analog, digital,
and/or optical signals, data, code, and/or text. The treatment
signal may be provided by, for example, vibrating a signaling
device located within the implantable housing. Alternatively, the
treatment signal may be generated within the implantable housing
and transmitted to a signaling device located external to the
patient, such as a personal digital recorder (PDA). In another
embodiment, the sensor signal is transmitted to an external device,
such as, for example, a PDA, which includes a processor and
signaling device to generate a processor output and provide a
treatment signal to the patient. These and other embodiments are
described in greater detail below.
[0089] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes one or more
signaling devices. In one embodiment, the signaling device includes
a buzzer, an alarm, a display, a computer, a telephone, or a PDA,
such as a Palm Pilot, or Handspring Visor. The signaling device may
be operable to generate at least two treatment signals
distinguishable from one another by the patient. In one embodiment,
each signal is indicative of a different therapeutic treatment. The
treatment signal may be an electrical pulse, a vibration, a noise,
audio or visual data, including, but not limited to, instructions
on a display screen or light emitting diodes. In one embodiment,
the at least two treatment signals may include two numerical values
or designations, a numerical value and an electrical pulse or
vibration, multiple vibrations of varying amplitudes, durations, or
frequencies, or any combination of two or more of any of the
treatment signals described herein. In one embodiment, the
signaling device is a PDA that displays an instruction, such as
"take medication," "rest," or "call Doctor". These and other
embodiments are described in greater detail below.
I. THE SYSTEM
A. Stand-Alone System
[0090] FIG. 1 shows an apparatus for treating cardiovascular
disease, such as congestive heart failure, which includes an
implantable module 5 in accordance with one embodiment of the
invention. The implantable module 5 includes a housing 7 and a
flexible, electrically conductive lead 10. The lead 10 is
connectable to the housing 7 through a connector 12 that may be
located on the exterior of the housing. In one embodiment, the
housing 7 is outwardly similar to the housing of an implantable
electronic defibrillator and/or pacemaker system. Defibrillator and
pacemaker systems are implanted routinely in medical patients for
the detection and control of tachy- and bradyarrhythmias. The
flexible lead 10 is also generally similar to leads used in
defibrillator and pacemaker systems, except that a compact sensor
package 15 is disposed at or near the distal end 17 of the lead 10,
the opposite end from the connector 12 on the housing 7. The sensor
package 15 contains sensors to measure one or more physical
parameters. An electrical signal or another form of signal
indicative of these physical parameters is then transmitted along
the lead 10 through the connector 12 and to the housing 7. The
housing 7 includes a signal processor (not shown) to process the
signal received from the sensor package 15 via the lead 10. In
addition, the housing 7 may include telemetry or signaling devices
(not shown), to either communicate with an external device, or
signal the patient, or both. The elements inside the housing 7 may
be configured in various ways, as described below, to communicate
to the patient a signal, such as a treatment signal, indicative of
an appropriate therapy or treatment based at least in part on one
or more of the measured physical parameters.
[0091] FIG. 2 shows another embodiment in which the sensor package
or module 15 has distal 68 and proximal 70 anchoring mechanisms
configured to anchor the sensor package 15 within the atrial septum
of a patient's heart. FIG. 2 shows one embodiment of the implanted
internal module 5, in which the implanted internal module 5
includes a physiologic sensor package or module 15. The physiologic
sensor package 15 includes one or more sensors (not shown) and
their accompanying electronics (not shown). The implanted module 5
also includes a flexible lead 10. The flexible lead 10 has a distal
end 17 and an indifferent electrode 14. A header or connector 12
connects the flexible lead 10 and housing 7 of the implanted module
5. The housing 7 contains electronics (not shown) and other
components (not shown) for communicating with an external module
(not shown). One embodiment showing the contents of the housing 7
is illustrated in FIG. 3.
[0092] As shown in FIG. 3, in one embodiment housing 7 includes a
power supply, a CRM, and a signal processing and patient signaling
modules. The CRM is configured to provide an electrical stimulus,
such as a pacing signal, to the patient's heart, and receive a
sensor signal from implanted sensors (not shown). In one
embodiment, the CRM is configured to control a defibrillator. The
signal processing module is coupled to at least one sensor that
provides a signal indicative of the fluid pressure within the left
atrium of the heart. The signal processing module may also be
configured to control a distally implanted CRM, or sensor package
or module, as described in greater detail herein.
[0093] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease at least one housing. In
one embodiment, the housing includes a shape that is flat and oval.
In another embodiment, the shape is cylindrical, rectangular,
elliptical, or spherical. One of skill in the art will understand
that a variety of other shapes suitable for implantation can also
be used. In one embodiment, the housing is about 20 mm by about 30
mm, about 10 mm by about 20 mm, or about 5 mm by about 10 mm. In
one embodiment, the housing is about 5 mm thick. In one embodiment,
the housing is implanted in the medical patient near the shoulder.
In another embodiment, the housing has dimensions suitable for
containing at least some components for controlling, powering
and/or communicating with a pacemaker and suitable for implantation
inside of the body, as is well known to those of skill in the art.
In another embodiment, the housing includes: an antenna, or a coil;
a power source, including but not limited to a battery or a
capacitor; a signal processor; a telemetry apparatus; a data
memory; or a signaling device. In one embodiment, the apparatus is
powered by an external power source through inductive, acoustical,
or radio frequency coupling. In one embodiment, power is provided
using electromagnetic emissions emitted from an electrical coil
located outside the body. In one embodiment, power and data
telemetry are provided by the same energy signal. In another
embodiment, an electrical coil is implanted inside the body at a
location under the skin near the patient's collarbone. In another
embodiment, an electrical coil is implanted inside the patient's
body at other locations. For example, in one embodiment, the coil
is implanted under the skin in the lower abdomen, near the groin.
One of skill in the art will understand that the device can be
implanted in a variety of other suitable locations.
[0094] As described above and in other embodiments herein, a system
for treating cardiovascular disease in a medical patient may
include at least one physiological sensor used to generate a signal
indicative of a physiological parameter on or in the patient's
body. The system includes signal processing apparatus operable to
generate a signal, such as a processor output, indicative of an
appropriate therapeutic treatment, which is based upon the signal
generated by the physiological sensor. In one embodiment, the
system also includes a patient signaling device, which is used to
communicate the signal indicative of the appropriate therapeutic
treatment, such as a treatment signal, to the patient.
[0095] In one embodiment, the physiological sensor is a pressure
transducer that is positioned to measure pressures within the
patient's left atrium. Signals from the pressure sensor are
monitored continuously or at appropriate intervals. Information is
then communicated to the patient corresponding to appropriate
physician-prescribed drug therapies. In one embodiment, the
information is the treatment signal. In many cases, the patient may
administer the drug therapies to him or herself without further
diagnostic intervention from a physician.
[0096] FIG. 4 shows one embodiment of a system for treating
cardiovascular disease 9. The system 9 includes an implantable
module 5, such as that described with reference to FIG. 2, and an
external patient advisory module 6, such as that described below
with reference to FIG. 5. During system 9 operation, radio
frequency signals are carried by a lead 10 between a pressure
sensor package 15 located near the distal end 17 of the lead 10,
and a housing 7 of an implantable module 5. The lead 10 includes an
indifferent electrode 14. The circuitry inside the housing 7
includes an antenna coil (not shown). In this embodiment, signals
are communicated between the implantable module 5 and an external
device, such as a patient advisory module 6, via the antenna coil
of the housing 7 and a second external coil (not shown) coupled to
the external device 6.
[0097] In one embodiment, the housing 7 contains a battery (not
shown) that powers the implantable device 5. In another embodiment,
the implanted device 5 receives power and programming instructions
from the external device 6 via radio frequency transmission between
the external and internal coils. The external device 6 receives
signals indicative of one or more physiological parameters from the
implanted device 5 via the coils as well. One advantage of such
externally powered implantable device 5 is that the patient will
not require subsequent surgery to replace a battery. In one
embodiment of the present invention, power is required only when
the patient or the patient's caregiver initiates a reading. In
other situations, where it is desired to obtain physiological
information continuously, or where it is desired that the implanted
device 5 also perform functions with higher or more continuous
power requirements, the housing 7 may also contain one or more
batteries. As described below, the housing 7 may also contain
circuitry to perform additional functions that may be
desirable.
[0098] FIG. 5 shows one embodiment of a patient advisory module 6.
In one embodiment, the patient advisory module 6 includes a
palm-type computer with added hardware and software. Referring to
FIG. 5, a patient advisory module 6 includes a radio frequency
telemetry module 164 with an associated coil antenna 162, which is
coupled to a processing unit 166. In one embodiment, the processing
unit 166 includes a palm-type computer, or personal digital
assistant (PDA), as is well known to those of skill in the art. In
one embodiment, the patient advisory module 6 powers the implanted
apparatus (not shown) with the telemetry hardware module 164 and
coil antenna 162. In another embodiment, the patient advisory
module 6 receives physiological signals from the implanted
apparatus by wireless telemetry through the patient's skin.
[0099] The patient advisory module 6 may include an RF unit 168 and
a barometer 112 for measuring the reference atmospheric pressure.
In one embodiment, the RF unit 168 and barometer are located within
the telemetry module 164, although they can be integrated with the
processing unit 166 as well. The signal processing unit can be used
to analyze physiologic signals and to determine physiologic
parameters. The patient advisory module 166 may also include data
storage, and a sub-module that contains the physician's
instructions to the patient for therapy and how to alter therapy
based on changes in physiologic parameters. The parameter based
physician's instructions are typically referred to as "the dynamic
prescription." The instructions are communicated to the patient via
the signaling module 166, or another module. The patient advisory
module 166 is located externally and used by the patient or his
direct caregiver. It may be part of system integrated with a
personal digital assistant, a cell phone, or a personal computer,
or as a Stand-Alone device. In one embodiment, the external patient
advisory module comprises an external telemetry device, a signal
processing apparatus, and a patient signaling device. In one
embodiment, the patient advisory module is operable to obtain the
sensor signal from the implantable sensor by telemetry through the
patient's skin; obtain the atmospheric pressure from the barometer;
and adjust the sensor signal indicative of a fluid pressure based
at least in part upon the atmospheric pressure obtained by the
barometer so that the adjusted sensor signal indicates the fluid
pressure within the left atrium of the heart relative to the
atmospheric pressure.
[0100] In one embodiment, the physiologic signals are analyzed and
used to determine adjustable prescriptive treatment instructions
that have been placed in the patient advisory module 6 by the
patient's personal physician. Communication of the prescriptive
treatment instructions to the patient may appear as written or
graphic instructions on a display of the patient advisory module 6.
These treatment instructions may include what medications to take,
dosage of each medication, and reminders to take the medications at
the appropriate times. In one embodiment, the patient advisory
module 6 displays other physician-specified instructions, such as
"Call M.D." or "Call 911" if monitored values become critical.
[0101] A third module of this embodiment is designed for physician
use. The third module is used to program the dynamic prescription
and communicate it or load it into the patient advisory module 166.
The third module may also contain stored data about the patient,
including historical records of the physiologic signals and derived
parameters transmitted from the patient implant and signaling
modules. The third module may also communicate with external
databases. In one embodiment, the third module is a physician input
device, and includes a personal computer, a PDA, a telephone, or
any other such device as is well known to those of skill in the
art.
[0102] In one embodiment, the second module (e.g., the patient
advisory module 166) is in the form of one or more implants.
[0103] In one embodiment of the present invention, the first
implant module (such as, for example, implantable module 5 of FIG.
1 and FIG. 2) may also contain an implant therapy unit, or ITU. The
ITU generates an automatic therapy regime based upon the programmed
dynamic prescription. The therapy may include, but is not limited
to, a system for releasing bioactive substances from an implanted
reservoir, a system for controlling electrical pacing of the heart,
and controllers for ventricular or other types of cardiac assist
devices. For example, in one embodiment the sensor package is
placed across the intra-atrial septum and serves as the atrial lead
of a multichamber pacemaker. The physiologic sensor information is
used to adjust pacing therapy such that pacing is performed only
when needed to prevent worsening heart failure. One skilled in the
art will appreciate that many systems or devices that control the
function of the cardiovascular system may be used in accordance
with several embodiments of the current invention.
[0104] In one embodiment of the invention, the advisory module 6 is
programmed to signal the patient when it is time to perform the
next cardiac status measurement and to take the next dose of
medication. It will be recognized by those skilled in managing CHF
patients that these signals may help the many patients who have
difficulty taking their medication on schedule. Although treatment
prescriptions may be complex, one embodiment of the current
invention simplifies them from the patient's perspective by
providing clear instructions. To assure that information regarding
the best treatment is available to physicians, professional
cardiology organizations such as the American Heart Association and
the American College of Cardiology periodically publish updated
guidelines for CHF therapy. These recommendations can serve as
templates for the treating physician to modify to suit individual
patient requirements. In one embodiment, the device routinely
uploads data to the physician or clinic, so that the efficacy of
the prescription and the response to parameter driven changes in
dose can be monitored. This enables the physician to optimize the
patient's medication dosage and other important treatments without
the physician's moment-to-moment intervention.
[0105] In various embodiment of the invention, a device and method
for dynamically diagnosing and treating cardiovascular illness in a
medical patient are provided. In one embodiment, at least one
physiological sensor is used to generate a signal indicative of a
physiological parameter. In another embodiment, signal processing
apparatus operable to generate a signal indicative of an
appropriate therapeutic treatment based, at least in part, upon the
signal generated by the physiological sensor, is also provided. In
another embodiment a patient signaling device used to communicate
the signal indicative of the appropriate therapeutic treatment to
the patient is provided as well.
[0106] In one embodiment, a device and method for continuously or
routinely monitoring the condition of a patient suffering from
chronic cardiovascular disease are provided. As will be described
in detail below, a system incorporating various embodiments of the
invention monitors various physiologic parameters, such as the
patient's left atrial pressure. Depending upon the magnitude of or
changes in this pressure, for example, the system communicates a
signal to the patient indicative of a particular course of therapy
appropriate to manage or correct, as much as possible, the
patient's chronic condition. In some embodiments, physician
instructions and automated therapy are provided.
[0107] In one embodiment, the physiological sensor generates a
signal indicative of a physiological parameter on or in the
patient's body. In one embodiment, the signal processing apparatus
generates a signal indicative of an appropriate therapeutic
treatment based at least in part upon the signal generated by the
physiological sensor. The patient signaling device may generate
signals indicative of therapeutic treatments or courses of action
the patient can take to manage or correct, as much as possible, the
patient's condition.
[0108] In one embodiment, this method includes the steps of
implanting one or more physiological sensors substantially
permanently within the patient, operating the physiological sensor
to generate a signal indicative of a physiological parameter,
processing this physiological signal to generate a signal
indicative of an appropriate therapeutic treatment, and
communicating the appropriate therapeutic treatment to a user. In
one embodiment, the user includes, but is not limited to, the
patient, a caregiver, a medical practitioner or a data collection
center.
[0109] In another embodiment, the system is combined with or
incorporated into a CRM system, with or without physiologic rate
control, and with or without backup cardioversion/defibrillation
therapy capabilities.
[0110] In one embodiment, at least one indication of congestive
heart failure (CHF) is monitored. Elevated pressure within the left
atrium of the heart is the precursor of fluid accumulation in the
lungs, which results in signs and symptoms of acute CHF. Mean left
atrial pressure in healthy individuals is normally less than or
equal to twelve millimeters of mercury (mm Hg). Patients with CHF
that have been medically treated and clinically "well compensated"
may generally have mean left atrial pressures in the range from 12
to 20 mm Hg. Transudation of fluid into the pulmonary interstitial
spaces can be expected to occur when the left atrial pressure is
above about twenty-five mm Hg, or at somewhat more than about
thirty mm Hg in some patients with chronic CHF. Pulmonary edema has
been found to be very reliably predicted by reference to left
atrial pressures and less well correlated with conditions in any
other chamber of the heart. Thus, the methods and apparatus of
several embodiments of the invention may prove very useful in
treating and preventing pulmonary edema and other adverse
conditions associated with CHF. Pressure in the pulmonary veins,
pulmonary capillary wedge position, and left ventricular end
diastolic pressure (LVEDP) are generally indicative of left atrial
pressure and are commonly used as surrogates of LAP. There are,
however, specific conditions, that are well known to those skilled
in the art, including cardiologists and physiologists, where these
surrogates vary substantially from LAP and may be less predictive
of impending heart failure. One example of such a condition is
mitral valve stenosis where pulmonary edema develops despite a
normal LVEDP due to a significant pressure gradient across the
mitral valve. Other surrogate pressures that also, on specific
occasion, indicate LAP include, but are not limited to: the
pulmonary artery diastolic (PAD) or algorithms that estimate PAD
from the right ventricular waveform, the right ventricular end
diastolic, and the right atrial pressure.
[0111] An embodiment of the invention includes a permanently
implanted device designed to define the presence of worsening CHF
hours to days before the onset of symptoms and to provide for early
preventative treatment according to the physician's individualized
prescription. As such, an embodiment of the invention includes an
integrated patient therapeutic system that determines therapeutic
dosages for an individual patient based at least in part on
internal physiologic signals. In another embodiment, the system
consists of a small implantable sensor device and an external
patient advisory module comprising a personal data assistant (PDA)
and a telemetry module. The sensor system may be implanted into the
patient's left atrial chamber by a transseptal catheterization
procedure. There are already several thousand physicians in the
U.S. and abroad with the experience and skills required for such
device implantation. The implantation procedure can be performed on
an outpatient basis in a hospital's cardiac catheterization
laboratory. The implant may alternatively be placed at the time of
open-heart or minimally invasive valve or bypass surgery where the
surgeon, under direct or laparoscopic vision, positions the device
in the left atrium, left atrial appendage, or an adjacent pulmonary
vein.
[0112] In one embodiment, the sensor system measures a left atrial
pressure waveform, core body temperature and a cardiac electrogram,
such as the intra cardiac electrogram (IEGM). Elevated left atrial
pressure is the most accurate predictor of impending CHF, often
preceding clinical symptoms by hours to days. Other embodiments of
the left atrial pressure waveform may be used to diagnose a number
of conditions, as listed in FIGS. 6A-6C. Core temperature is often
depressed in acute CHF, but elevated prior to the development of
fever in response to an infection, making core temperature a useful
parameter for differentiating between these common conditions with
similar symptoms but which require different treatments. The
intracardiac electrogram may be useful in diagnosing arrhythmias
and precipitating causes of worsening CHF.
[0113] FIG. 7 shows how left and right atrial pressure measurements
may be combined with IEGM and core temperature measurement to
diagnose a number of cardiac and non-cardiac conditions. The list
of diagnostic states in FIG. 7 is exemplary, and by no means
exhaustive of all the potential diagnostic states definable by the
given parameters. Multiple states can exist simultaneously, for
example, moderate CHF and rapid atrial fibrillation. The measured
parameters can be used over large populations to define the
probability of any given diagnostic state. Each diagnostic state
may have a unique treatment. For example, mild CHF may be treated
by increasing diuretic therapy, whereas rapid atrial fibrillation
is treated with a drug that blocks AV node conduction. Many of the
states listed can contribute to worsening CHF.
[0114] 1. Implantation and Anchoring
[0115] a. Placement and Anchoring in the Left Atrium
[0116] In one embodiment, such as that illustrated in FIG. 8, an
implantable device is implanted percutaneously in the patient by
approaching the left atrium 36 through the right atrium 30,
penetrating the patient's atrial septum 41 and positioning one or
more physiological sensors 15 in the atrial septum 41, on the
septal wall of the left atrium 36, or inside the patient's left
atrium 36. FIG. 8 shows an embodiment in which a sensor package 15
is deployed across the atrial septum 41. The sensor lead 10 is
coupled to a physiological sensor or sensors 15 and anchoring
apparatus at the lead 10 distal end. The anchoring apparatus
includes a distal foldable spring anchor 68 that expands in
diameter upon release and is located at or near the distal tip of
the sensor 15, and a proximal foldable spring anchor 70. The distal
and proximal anchors 68, 70 are sufficiently close together that
when deployed the two anchors 68, 70 sandwich the intra-atrial
septum 41 between them, thus fixing the sensor/lead system to the
septal wall. The intra-atrial septum 41 is typically between about
1 and about 10 mm thick. In one embodiment, the anchors 68, 70 are
made of a highly elastic biocompatible metal alloy such as
superelastic nitinol. The lead 10 may contain a lumen that exits
the lead 10 at its proximal end. A stiffening or bending stylet can
be insert in the lumen to aid in passage of the sensor(s) and lead
15, 10. After a transseptal catheterization has been performed, a
sheath/dilator system of diameter sufficient to allow passage of
the sensor/lead system is placed from a percutaneous insertion site
over a guidewire until the distal end of a sheath 67 is in the left
atrium 36. Left atrial position can be confirmed under fluoroscopy
by contrast injection, or by the pressure waveform obtained when
the sheath 67 is connected to a pressure transducer. To aid the
procedure, the sheath 67 may include a proximal hemostasis valve to
minimize air entrainment during device insertion. A side port with
a stopcock is useful to aspirate any remaining air and to inject
radiographic contrast material. Additionally, later sheath 67
removal may be facilitated by using a "peel-away" type of sheath.
These features of vascular sheaths are commercially available and
well know to those familiar with the art. With the spring anchors
68, 70 folded and forming a system with minimal diameter, the
system is loaded into the sheath 67 and advanced until the distal
spring 68 just exits the sheath 67 in the left atrium 36 and is
thus deployed to its sprung diameter. The sheath 67 is carefully
withdrawn without deploying the proximal anchor 70 and the sheath
67 and sensor/lead system are withdrawn as a unit while contrast is
injected through the sheath 67 around the sensor lead until
contrast is visible in the right atrium 30. The proximal sheath 67
is further withdrawn, allowing the proximal anchor 70 to spring to
its unloaded larger diameter, thus fixing the distal portion of the
sensor lead to the septum 41.
[0117] It will also be apparent that, in several embodiments, a
similar sensor/lead system can be inserted through an open
thoracotomy or a minimally invasive thoracotomy, with the anchoring
system fixating the sensor/lead to a location such as the free wall
of the left atrium, the left atrial appendage, or a pulmonary vein,
all of which provide access to pressures indicative of left atrial
pressure.
[0118] In one alternative embodiment, a flexible lead 10 is
partially advanced into a pulmonary vein 50 connected to the left
atrium 36 such that one or more physiological sensors 15 disposed
on the flexible lead 10 a predetermined distance from its distal
end 17 are positioned within the left atrium 36 or the pulmonary
vein 50, as shown in FIG. 9. In another embodiment, the distal
portion 17 of the flexible lead 10 is partially advanced into the
left atrial appendage such that anchoring apparatus will be
occlusive of the appendage, for example as taught by Lesh et al. in
U.S. Pat. No. 6,152,144, incorporated by reference herein. The
physiologic sensors 15 are positioned on the lead 10 proximal to
the occlusive anchors so that they sense conditions in the left
atrium.
[0119] In other embodiments, such as those shown in FIG. 12 and
FIG. 14, a first lead component 53 includes an anchoring apparatus,
for example, a helical screw 57, which is advanced to the atrial
septum 41. The anchoring apparatus is deployed to anchor the first
lead component 53 into the patient's atrial septum 41. A second
lead component 60 includes a physiological sensor, for example, a
pressure transducer 62, which is advanced along the first lead
component 53 until the second lead component 60 is in a position
such that the physiological sensor is positioned within the
patient's left atrium 36.
[0120] b. Implantation in the Left Atrium
[0121] Referring to the embodiment depicted in FIG. 8, the system
is implanted through the left atrial septum 41 such that the
pressure sensor 15 is exposed to the pressure in the left atrial
chamber 36 of the heart. The left atrial septum 41 can be accessed
from the right atrium 30 through the inferior or superior vena cava
35, 28, as is well known to those skilled in the arts of, for
example, pacemaker lead placement, catheter ablation for control of
arrhythmias originating in the left atrium or pulmonary veins,
percutaneous repair of the mitral valve, and percutaneous closure
of an atrial septal defect. In one embodiment, the flexible lead 10
and pressure transducer 15 are anchored to the atrial septum 41.
This placement can be achieved using vascular access techniques
that are well-known to those familiar with the performance of
invasive cardiovascular procedures, in particular, interventional
cardiologists, electrocardiologists, and cardiovascular surgeons.
These procedures are commonly performed with the aid of
visualization techniques, including standard fluoroscopy, cardiac
ultrasound, or other appropriate visualization techniques used
alone or in combination.
[0122] Access to the central venous circulation may be achieved by
use of the standard Seldinger technique through the left or right
subclavian vein, the right or left internal jugular vein, or the
right or left cephalic vein. Alternatively, access may be made via
the Seldinger technique into the right femoral vein. In either
case, a Brockenbrough catheter and needle are used to pierce the
atrial septum 41 for access to the left atrium 36, as described
below.
[0123] i. Superior Venous Access (Subclavian or Internal Jugular
Vein)
[0124] FIG. 10 provides a schematic sectional view of the patient's
heart 33 and shows the apparatus used to access the left atrium 36.
FIG. 10 depicts an access assembly 18 comprising a Brockenbrough
catheter 20 inside a sheath 22, with a flexible guidewire 25
residing within the Brockenbrough catheter 20. As FIG. 10
indicates, the access assembly has been placed through the superior
vena cava 28 into the right atrium 30 of the heart 33. FIG. 10 also
shows the inferior vena cava 35, the left atrium 36, the right
ventricle 37, the left ventricle 40, the atrial septum 41 that
divides the two atria 30, 36, and the valves 42 between the right
atrium 30 and right ventricle 37, and the left atrium 36 and left
ventricle 40. The reader will appreciate that the view of FIG. 10
is simplified and somewhat schematic, but that nevertheless FIG. 10
and the other views included herein will suffice to illustrate
adequately the placement and operation of an embodiment of the
present invention.
[0125] ii. Placement of the Lead
[0126] With the access assembly 18 in place within the right atrium
30, the Brockenbrough catheter 20 is used to pierce the atrial
septum 41 by extending the Brockenbrough needle (not shown) through
the atrial septum 41 into the left atrium 36. In the figures, the
atrial septum 41 has been pierced by the needle, the catheter 20
has been advanced over the needle, and the needle has been
withdrawn from the catheter 20, leaving the catheter 20 in place
inside the left atrium 36. Optionally, a guidewire 25 may be
advanced through the needle into the left atrium 36 before or after
advancing the catheter 20, or it may be placed into the left atrium
36 through the catheter 20 alone after the needle has been
withdrawn. A lead placement procedure is described above.
[0127] As indicated by the arrows 45 in FIG. 10, the sheath 22 may
extend into the left atrium 36, or it may remain on the proximal
side of the atrial septum 41 within the right atrium 30. FIG. 10
shows the guidewire 25 extended from the end of the Brockenbrough
catheter 20 to secure continuous access into the left atrium 36. As
depicted therein, the guidewire 25 has a curled, "pig-tail" style
distal tip 48 to better secure the guidewire 25 within the left
atrium 36 and to safeguard against inadvertent withdrawal through
the atrial septum 41. Alternatively, a "floppy tip" guide wire may
be used, which can be safely advanced well into one of the
pulmonary veins, again to safeguard against inadvertent withdrawal
through the atrial septum 41. Once the guidewire 25 is securely in
place in the left atrium 35, the Brockenbrough catheter 20 may be
withdrawn so that the flexible lead 10 may be placed through the
peel-away sheath 22.
[0128] With the guidewire 25 securely in place with its distal tip
48 inside the left atrium 36, the flexible lead 10 may be advanced
into the left atrium 36. The flexible lead 10 might itself include
a central lumen configured to receive the proximal end of the
guidewire 25, thereby allowing the flexible lead 10 to be advanced
down the guidewire 25 toward the left atrium 36. More commonly, an
exchange catheter, which may be in the form of a peel-away sheath
22, will be advanced down the guidewire 25 and placed into the left
atrium 36, the guidewire 25 may then be withdrawn, after which the
flexible lead 10 will be advanced down the exchange catheter and
into position.
[0129] In one embodiment, a peel-away sheath 22 is used to allow
the sheath to be removed once the distal end of the lead 10 is
implanted. The peel-away feature is not used if the proximal end of
the lead 10 is detachable from the coil housing assembly (described
above). In this case, a non-peel-away sheath with proximal
hemostasis valve and side port as described above can be used, and
simply slid off the proximal end of the lead 10 prior to attaching
the lead 10 to the coil/housing assembly.
[0130] iii. Anchoring the Sensor and Lead
[0131] Once the pressure transducer 15 of the flexible lead 10 is
positioned within the left atrium 36, the lead 10 should be
anchored in place to ensure that the pressure transducer 15 stays
reliably and permanently in the desired location.
[0132] One method for anchoring the flexible lead 10 in place is
depicted in FIG. 9, which is a somewhat schematic depiction of the
major structures of the heart. FIG. 9 shows the four pulmonary
veins 50 that connect to the left atrium 36. In the particular
apparatus depicted in FIG. 9, the flexible lead 10 includes a
pressure transducer 15 located on the body of the lead 10 a
predetermined distance proximal of the distal end 17 of the lead
10.
[0133] Referring back to FIG. 9, the distal end 17 of the flexible
lead 10 in this embodiment can be bent by the operator in much the
same way as a distal tip such as might be found on a steerable
angioplasty guidewire or another similar device. This feature
assists the operator in steering the flexible lead 10 into a
selected one of the pulmonary veins 50, with the pressure
transducer 15 disposed within the interior space of the left atrium
36, or even within the pulmonary vein itself. Placement of the
pressure transducer 15 within the pulmonary vein is effective
because pressures within the pulmonary vein are very close to
pressures within the left atrium. It will be appreciated by those
skilled in the art that visualization markers (not shown) may be
provided at appropriate locations on the flexible lead 10 to assist
the operator in placing the device as desired. With the flexible
lead 10 in place as shown, the body's own natural healing mechanism
may permanently anchor the flexible lead 10 in place both at the
penetration site through the atrial septum 41, and where the
flexible lead 10 contacts the interior surface of the pulmonary
vein 50 in which the tip of the lead 10 resides. The pressure
transducer 15 might also be placed at locations such as the left
atrial appendage (not shown in FIG. 9) where the pressure is nearly
the same as the left atrium 36, or the left ventricular cavity,
where at identifiable phases of the cardiac cycle the pressure is
momentarily nearly the same as that in the left atrium 36.
[0134] FIG. 11 and FIG. 12 show alternative methods and devices for
anchoring the pressure transducer 15 in a location appropriate for
measuring pressures within the left atrium 36. The lead in this
embodiment includes a helical screw 57 for anchoring the lead to
the atrial septum 41. Similar configurations are used in some leads
for pacemakers and thus may be familiar to those skilled in the
art.
[0135] Referring now specifically to FIG. 11, the guidewire 25 is
shown positioned across the atrial septum 41 between the left
atrium 36 and the right atrium 30. A first lead component 53 is
delivered over the guidewire through an appropriate guiding
catheter 55 or sheath. This first lead component 53 includes a
helical screw 57 on its exterior surface. The helical screw 57 is
advanced into the tissue of the atrial septum 41 by applying torque
to the shaft of the first lead component 53. The helical screw 57
could also be coupled to a hollow or solid cylindrical mandrel (not
shown), or to a spirally wound mandrel (also not shown) disposed
along substantially the entire length of the first lead component.
When the helical screw 57 has been turned and advanced sufficiently
into the atrial septum 41, the guidewire 25 and guiding catheter
may then be withdrawn leaving the first lead component 53 anchored
securely in place.
[0136] iv. Two-Component Lead with Optional Second Pressure
Transducer
[0137] In one embodiment, a second lead component 60 is advanced as
shown in FIG. 12 through a central lumen in the first lead
component 53. The first and second lead components 53, 60 are sized
and configured so that when the second lead component 60 is fully
advanced with respect to the first lead component 53, a left atrial
pressure transducer 62 at the end of the second lead component 60
protrudes by an appropriate predetermined amount into the left
atrium 36. In one embodiment, the second lead component 60 is then
securely fixed with respect to the first lead component 53.
[0138] It should be noted that the embodiments depicted in FIG. 11
and FIG. 12 includes a second pressure transducer 65 on the
exterior of the first lead component 53 that may be exposed to
pressure within the right atrium 30. This illustrates, in a
simplified way, the general principle, in which a pressure
transducer is used to measure fluid pressure within the left
atrium, but in which one or more additional transducers or sensors
may also be used to detect a physiologic condition other than left
atrial pressure. These physiologic conditions may include pressures
in locations other than the left atrium 36, and physical parameters
other than pressure.
[0139] v. Alternative Anchoring Systems and Methods
[0140] FIG. 8 and FIG. 13 through FIG. 16 show embodiments of the
flexible lead 10, in which folding spring-like fins or anchors
deploy to anchor the lead in place in the atrial septum 41.
Referring specifically to FIG. 13, a first lead component 53 is
advanced through a sheath 67, the sheath 67 having been advanced
across the atrial septum 41. In this embodiment, the first lead
component 53 includes folding distal anchors 68 and proximal
anchors 70 that lie folded and are held in place inside the
interior lumen of the sheath 67. When the first lead component 53
and sheath 67 are properly positioned, which will generally involve
the use of fluoroscopy or an alternative technique for imaging, the
operator may carefully withdraw the sheath 67 from around the first
lead component 53. As the distal and proximal anchors exit the
sheath 67, they deploy themselves (as depicted in FIG. 8) on either
side of the atrial septum 41, thereby anchoring the first lead
component 53 securely in place. Similar anchors are sometimes used
with leads for pacemakers and other medical devices where permanent
anchoring is desired, and the operation of these anchors thus will
not be entirely unfamiliar to the knowledgeable reader.
[0141] Referring now to FIG. 14, a second lead component 60 is
advanced through a central lumen of the first lead component 53
after the guidewire 25 (see FIG. 15 and FIG. 16) and sheath 67 are
removed. As in the previous embodiment, a left atrial pressure
transducer 62 is carried at the distal end of the second lead
component 60. Again, the first and second lead components 53, 60
are sized and configured with respect to one another so that the
left atrial pressure transducer 62 protrudes from the first lead
component 53 an appropriate amount into the left atrium 36. In
addition, as in the previous embodiment, a second pressure
transducer 65 on the exterior of the first lead component 53 allows
for the measurement and transmittal of pressure within the right
atrium 37.
[0142] Other anchoring methods may be devised by those skilled in
the relevant arts. Moreover, approaches have been described by
which the lead is positioned between the left atrium and an exit
site from the patient's superior venous circulation. Alternate lead
routes and exit sites may find use as well.
[0143] vi. Surgical Methods of Device Implantation
[0144] As described above, percutaneous transvenous implantation
methods are used in accordance with several embodiments of the
current invention. One skilled in the art will understand that
alternative lead routes and exit sites from the venous system may
also be used. One important class of alternative implantation
methods consists of surgical implantation through the wall of the
heart, either directly into the left atrium through the left atrial
free wall or left atrial appendage, into the left atrium via a
pulmonary vein, into the left atrium through the intra-atrial
septum via the right atrial free wall, or directly into a pulmonary
vein.
[0145] In one embodiment, the pressure transducer is implanted in
the atrial free wall or in the wall of the atrial appendage. As
described above, in one embodiment, at these locations the pressure
sensing surface of the transducer is exposed to left atrial
pressure, and the body of the transducer extends through the wall
of the atrium or atrial appendage. A flexible lead from the
implanted transducer provides signal connection to a telemetry
antenna coil that the surgeon implants near the surface of the
skin. In another embodiment, this coil may be connected directly to
the implanted pressure transducer on the outside surface of the
heart, without need for a flexible lead. In yet another embodiment,
the flexible lead provides signal connection to a CRM generator
housing located near the surface of the skin.
[0146] c. Pulmonary Vascular Implant
[0147] Vascular stents are implants that are deployed in blood
vessels to support the size of the vascular channel and maintain
adequate blood flow. A stent may also be used to anchor another
type of device in a fixed location within the cardiovascular
system. U.S. Pat. No. 5,967,986, incorporated by reference herein,
describes a stent coupled to one or more pressure transducers for
the purpose of measuring blood flow in a vessel. In one embodiment
of the current invention, a stent is used to support and anchor the
sensor measuring a signal indicative of left atrial pressure. As
mentioned above, the pressure in the pulmonary veins is
substantially identical to that in the left atrium. Thus, in one
embodiment of this invention, the pressure sensor is anchored in a
pulmonary vein by means of a stent expanded within the vein.
[0148] In one embodiment of the current invention, a method and
apparatus for continuous ambulatory detection, diagnosis and
treatment of acute congestive heart failure is provided. It will be
understood that the current invention may be implemented using
digital signal processing methods in which various input signals
are sampled and the described procedures are performed on a set of
samples. Hence, a periodic determination of the physiological
parameter of interest is within the definition of the term
continuous. In one embodiment, a percutaneously implantable system
comprises a hermetically sealed pressure transducer/communications
module mounted on an unexpanded vascular stent-like member. In one
embodiment, the stent-like member is a cylindrical vascular stent
such as a balloon expandable or self-expanding metallic stent
similar to those used to treat vascular stenosis such as
atherosclerotic stenosis of a coronary or peripheral artery. The
pressure transducer/communications module is mechanically coupled
to the unexpanded stent and the stent/transducer module is mounted
on a delivery catheter constituting a stent/transducer delivery
system. The stent/transducer delivery system is percutaneously
inserted into a patient's body via the venous or arterial
system.
[0149] In one embodiment, the delivery system courses over a guide
wire that has been positioned from proximal to distal, starting
outside the patient, percutaneously entering into the venous system
and into the right atrium, through the right ventricle and into a
branch of the pulmonary artery. The stent/transducer module is then
advanced over the guide wire into the selected branch of the
pulmonary artery that is approximately the diameter of the expanded
stent/transducer module.
[0150] In another embodiment, a standard transseptal
catheterization procedure is performed to place a guide wire that
courses from proximal to distal starting outside the patient
percutaneously into the venous system into the right atrium, across
the intra-atrial septum, into the left atrium and finally into one
of the four pulmonary veins. The stent/transducer delivery system
is then advanced over the guide wire until the unexpanded
stent/transducer is positioned in the pulmonary vein that is
approximately the diameter of the expanded stent/transducer module.
The stent is then expanded such that the cylinder described by the
stent is coaxially in contact with the vessel wall confining the
transducer/communications module so that its outer surface contacts
the vessel wall.
[0151] 2. Pressure Transducer
[0152] a. Pressure Sensor Locations
[0153] In one embodiment of the invention, the apparatus and/or
method for treating cardiovascular disease includes one or more
sensors, such as pressure sensors. In one embodiment, the pressure
sensor is located in the atrial septum, the left atrial appendage,
one of the pulmonary veins, or any other location in pressure
communication with the left atrium, for example, but not limited
to, the right atrium, the central veins, or any location as known
to those of skill in the art suitable for measuring a pressure
related to the pressure in the pulmonary veins, the pulmonary
capillary wedge pressure, the pulmonary artery diastolic pressure,
the left ventricular end diastolic pressure, or the right
ventricular end diastolic pressure. In one embodiment, the pressure
signal includes a pulmonary vein pressure, a pulmonary capillary
wedge pressure, a pulmonary artery diastolic pressure, a left
ventricular end diastolic pressure, a right ventricular end
diastolic pressure, right atrial pressure, or the pressure measured
in the intrathoracic space, or the central veins. In another
embodiment, the signal includes algorithms that estimate pulmonary
artery diastolic pressure from the right ventricular waveform, the
right ventricular end diastolic pressure, or the right atrial
pressure.
[0154] b. Pressure Sensor Design
[0155] In one embodiment, the physiological sensor includes a
pressure transducer. In one embodiment, the pressure transducer is
contained within a hermetically sealed sensor package, or module.
The sensor package may be provided in a wide range of sizes and
shapes. In one embodiment, the sensor package is cylindrical, and
is between about 1 mm and 5 mm long, and 3 mm in diameter. In
another embodiment, the sensor package is between about 5 mm and
about 15 mm long. In another embodiment the package is about 8 mm
long, and about 3 mm in diameter. In one embodiment the package is
less than about 1 mm in diameter. In another embodiment, the
package is less than about 10 mm long. Microsensors may also be
used. In one embodiment, the package may be rectangular, square,
spherical, oval, elliptical, or any other shape suitable for
implantation. In one embodiment, the sensor package is rigid, and
in another embodiment, the sensor package is flexible.
[0156] In one embodiment, the sensor package includes a titanium
cylindrical housing that is closed at one end by titanium foil
membrane. In one embodiment, the foil membrane is between about
0.001 to 0.003 inches, between about 0.003 inches and about 0.005
inches, or less than 0.001 inches thick. In another embodiment, the
foil membrane is between about 25 microns to about 50 microns
thick, and about 0.08 to 0.10 inches (about 2.0 to 2.5 mm) in
diameter. Foil diaphragms of this type have relatively low
compliance, meaning that they exhibit relatively little strain, or
displacement, in response to changes in pressure. For example, in
one embodiment, a 2.5 mm diameter by 50-micron thick titanium foil
diaphragm has a displacement at its center of only about 4.3
microns per mm Hg pressure change. Higher compliance is a
disadvantage for implantable pressure sensors because tissue
overgrowth can limit the relatively larger motion of a high
compliance diaphragm, causing errors in the sensed pressure
reading.
[0157] In one embodiment, resistive strain gauges are bonded to the
inside surface of the foil.
[0158] In one embodiment, the titanium cylindrical housing
comprises an application specific integrated circuit (ASIC or
"chip") or "measurement electronics." Measurement electronics are
contained within the housing, connected to the strain gauges by
fine gold wires. The other end of the housing is sealed by a
ceramic feed-through that is brazed to a titanium cylinder.
[0159] In one embodiment, the pressure of the gas sealed in the
cylinder is slightly lower than the lowest external pressure
anticipated, so that the net force on the foil will be inward under
normal conditions of operation, forming a concave membrane shape.
The advantage of maintaining a concave membrane shape throughout
the pressure range of operation is that it avoids potential
pressure measurement artifacts that are known to sometimes occur
when a pressure sensing membrane transitions between a concave and
a convex shape, a phenomenon known as "oil-canning." In one
embodiment, oil-canning is avoided by using a transducer diaphragm
that has low compliance, with low compliance as described above,
and that is nearly flat in the absence of a pressure differential.
In one embodiment, the diaphragm is about 2.0 to 2.5 mm in diameter
and is within about 25 microns of flat in the absence of a pressure
differential. In another embodiment, the diaphragm thickness is
maximized to maximize flatness and minimize compliance, consistent
with the sufficient compliance to derive a useable transducer
signal.
[0160] In one embodiment, the pressure sensor includes temperature
compensation so that pressure measurements will not be affected by
temperature change. This also provides the temperature at the site
of the sensor. In one embodiment, temperature compensation or
modulation is achieved by using multiple resistive strain gauges
arranged in a Wheatstone bridge, such that the electrical voltage
output of the bridge is proportional to the ratio of two or more
resistances, as is well known in the art of electrical
measurements. By selecting resistive strain gauges with
substantially identical temperature coefficients, the intrinsic
output of the bridge is made to be temperature independent.
However, the overall response of the pressure transducer may still
be temperature dependent due to other factors, such as the
different thermal expansions of the various components and contents
of the device. Another embodiment of temperature compensation
utilizes an internal thermometer consisting of, for example, a
resistor whose resistance depends upon temperature in a
reproducible way, and which is placed in a location isolated from
the transducer diaphragm so that its resistance does not depend on
pressure variations. Prior to implanting the device, calibration
data is collected consisting of the output of the transducer versus
pressure as a function of the reading of the internal thermometer.
After implantation, the signal from the internal thermometer is
used together with the transducer output and the calibration data
to determine the temperature compensated pressure reading. In one
embodiment, a band gap voltage reference is used to create a
current proportional to absolute temperature that is then compared
to the temperature-independent voltage reference. Such methods are
well-known in the art of CMOS integrated circuit design.
[0161] In one embodiment, the devices described herein are
configured similarly to a cardiac pacemaker, with a hermetically
sealed housing implanted under the patient's skin and a flexible
lead with a pressure transducer at its distal end. The housing
contains a battery, microprocessor and other electronic components,
including a patient signaling device and transcutaneous telemetry
means for transmitting programming information into the device and
for transmitting physiological data out to an external
programmer/interrogator.
[0162] One skilled in the art will understand that alternative
distributions of the components may be constructed in accordance
with several embodiments of the present invention. In one
alternative, the pressure sensing circuitry is incorporated into
the pressure transducer unit implanted in the heart, reducing the
number of conductors needed in the lead to as low as two.
[0163] In another embodiment, the signal processing, prescription
algorithms, and patient signaling components are located in a
device external to the patient's body in communication with the
implanted subcutaneous housing via one of various forms of
telemetry well known in the art, such as two-way radio frequency
telemetry.
[0164] In another embodiment, the pressure sensor is fabricated by
micro electromechanical systems (MEMS) techniques, as taught by,
for example U.S. Pat. No. 6,331,163, herein incorporated by
reference.
[0165] c. Sensor-Tissue Interaction Issues
[0166] In one embodiment, within several weeks after implantation,
the entire device is covered with new tissue, including fibrous
tissue and endothelium. A covering of endothelium is desirable
because it prevents the formation of blood clots that, if formed,
could break loose and cause a blocked artery elsewhere in the body,
most dangerously in the brain. A covering of fibrous tissue is also
a common component of the body's healing response to injury and/or
foreign bodies. An excessive growth of fibrous tissue on the left
atrial surface of the pressure sensor may be undesirable because it
may interfere with accurate transmission of fluid pressure in the
left atrium to the pressure sensitive diaphragm. In addition,
contraction of fibrous tissue over time may cause progressive
changes in the pressure waveform or mean value, which could
confound interpretation of the data.
[0167] i. Low Compliance Sensor Membrane
[0168] In one embodiment, the pressure transducer membrane is
designed to have very low compliance. In one embodiment, a low
compliance pressure transducer is fabricated using titanium foil as
described above. In another embodiment, a low compliance pressure
transducer is fabricated from, for example, silicon, using micro
electromechanical systems (MEMS) techniques. In yet another
embodiment, a coating is provided on the left atrial surface of the
pressure sensor.
[0169] ii. Coatings, Polishing, and Drug Eluting Surfaces
[0170] In one embodiment, a coating inhibits or minimizes the
formation of undesirable fibrous tissue, while not preventing the
beneficial growth of an endothelial covering. Coatings with these
properties are well known in the art of implanting medical devices,
particularly intravascular stents, into the blood stream. Surface
coating materials include, but are not limited to, paralene, PVP,
phosphoryl choline, hydrogels, albumen affinity, and PEO.
[0171] In one embodiment, at least some areas of the sensor package
and diaphragm are electropolished. Electropolished surfaces are
known by those skilled in the art to reduce the formation of
thrombosis prior to endothelialization, which leads to a reduced
burden of fibrotic tissue upon healing. All metallic intracoronary
stents currently approved for clinical use are electropolished for
this purpose.
[0172] Release of antiproliferative substances including radiation
and certain drugs are also known to be effective in stenting. Such
drugs include, but are not limited to, Sirolimus and related
compounds, Taxol and other paclitaxel derivatives, steroids, other
anti-inflammatory agents such as CDA, antisense RNA, ribozymes, and
other cell cycle inhibitors, endothelial promoting agents including
estradiol, antiplatelet agents such as platelet glycoprotein
IIb/IIIa inhibitors (ReoPro), anti-thrombin compounds such as
heparin, hirudin, hirulog etc, thrombolytics such as tissue
plasminogen activator (tPA). These drugs may be released from
polymeric surface coating or from chemical linkages to the external
metal surface of the device. Alternatively, a plurality of small
indentations or holes can be made in the surfaces of the device or
its retention anchors that serve as depots for controlled release
of the above mentioned antiproliferative substances, as described
by Shanley et al. in U.S. Publication No. 2003/0068355, published
Apr. 10, 2003, incorporated by reference herein.
[0173] d. Pressure Signal Detection
[0174] In one embodiment, the implanted portion of the device is
comprised of a plurality of up to n physiologic signal detection
sensors S described by the set:
[0175] {S.sub.1, S.sub.2, . . . S.sub.n}.
[0176] In one embodiment, S.sub.1, the first sensor, detects a
parameter that is indicative of left atrial pressure or S.sub.iLAP,
thus
[0177] {S.sub.iLAP, S.sub.2, . . . S.sub.n}.
[0178] Signals indicative of left atrial pressure can be pressure
signals measured at a variety of sites and may be detected by a
variety of pressure transducer types. The signals may be obtained
from locations in the cardiovascular system or adjacent to the
cardiovascular system known to be similar to or highly correlated
with direct pressure readings from the left atrium. Such locations
for obtaining pressure signals similar to the left atrium are well
known to those skilled in the art, such as Cardiologists. Locations
for sensing pressure include, but are not limited to, the left
atrium and its contiguous structures, the pulmonary veins, the
pulmonary capillary wedge or occlusion pressure, the pulmonary
artery diastolic pressure, and the left ventricular end diastolic
pressures. Other pressures indicative of left atrial pressure
include differential pressures such as the difference between the
left atria and the right atria, or the difference between the
pulmonary capillary wedge and right atrial pressures, as shown by
the correlation in FIG. 17. The individual signals comprising the
differential signal correlate independently with left atrial
pressure.
[0179] 3. Non-Pressure Sensors
[0180] a. Left Atrial Dimension
[0181] In one embodiment, the system may include one or more
additional sensors. In one embodiment, a non-pressure sensor is
also provided to generate a signal indicative of pressure in the
left atrium. Hemmingsson (U.S. Pat. No. 6,421,565), incorporated by
reference herein, describes such an implantable cardiac monitoring
devices as an A-mode ultrasound probe which is adapted to be
positioned in the right ventricle of a heart, and which emits an
ultrasound signal which is reflected from one cardiac segment of
the left ventricle of the heart, and the ultrasound probe receives
the resulting echo signal. The delay between the emission of the
ultrasound signal and the reception of the resulting echo is
measured, and from this delay a position of the cardiac segment is
determined. In one embodiment, an A-mode ultrasound probe is
deployed in the right atrium of a heart so that an ultrasound
signal is reflected from one or more cardiac segments of the left
atrium, either the atrial septal segment, the lateral wall segment,
or both. Increased left atrial pressure is known to cause in
increase in the volume of the left atrium by displacing the walls
of the left atrium away from each other. Thus, measurement of the
positions of one or more left atrial walls provides a signal
indicative of left atrial pressure, as described below, that can be
used to guide therapy for CHF.
[0182] Kojima (U.S. Pat. No. 4,109,644), incorporated by reference
herein, describes another implantable ultrasound transducer that
could be used in the manner described above to determine left
atrial dimension and thus derive a signal indicative of left atrial
pressure.
[0183] In one embodiment, the sensor comprises one pressure sensor,
a pressure sensor package, or module, with pressure sensor and
electronics, or a sensor package containing electronics, a pressure
sensor, and at least one non-pressure sensor. In one embodiment,
the at least one non-pressure sensor provides a signal indicative
of: an internal electrocardiogram; a temperature; a physical
dimension; an electrical resistance, such as, but not limited to, a
thoracic electrical impedance; a respiratory tidal volume; a
respiratory rate; lung acoustics; oxygen saturation; oxygen partial
pressure, including oxygen partial pressure in the left chamber or
the right chamber; or cardiac output. In another embodiment of the
invention, the non-pressure sensor measures: left atrial dimension,
cross-sectional area, or volume; left ventricular dimension,
cross-sectional area or volume; atrial septum position; velocity,
or acceleration. In one embodiment, a non-implanted sensor is
provided. In one embodiment, the non-implanted sensor includes: an
arterial pressure cuff, including an automated arterial pressure
cuff; and a weight scale. In one embodiment, two sensors are
provided, a first sensor and a second sensor. In one embodiment,
the first sensor measure a pressure in the heart and the second
sensor measures a non-pressure parameter, including, but not
limited to the parameters listed above. In one embodiment, the
second sensor is also a pressure sensor. In one embodiment, the
first sensor is located internal to the patient and the second
sensor is located external to the patient. Located "external", as
used herein, shall be given its ordinary meaning and shall also
mean located on the patient, in contact with the patient, or
located completely independent of the patient.
[0184] b. Core Temperature
[0185] Other non-pressure physiologic parameters may be used in
other embodiments. Casscells III, et al. (U.S. Pat. No. 6,454,707),
incorporated by reference herein, describe a method and apparatus
for predicting mortality in congestive heart failure patients by
monitoring body temperature and determining whether a downward
trend in temperature fits any predetermined criteria. The apparatus
described by Casscells et al. determines when death is imminent and
generates an alarm. In one embodiment of the present invention, the
trend in body temperature is used daily to adjust the patient's
therapy at an earlier point before any downward trend in
temperature becomes critical. In one embodiment, core body
temperature is measured at the atrial septum. In another
embodiment, core body temperature is measured at the site of a
measurement module located anywhere within the heart, heart
chambers, great vessels, or other locations within the thorax known
in the medical arts to maintain a temperature related in a
predictable way to core body temperature.
[0186] 4. Signals
[0187] a. Left Atrial Pressure Signals
[0188] In one embodiment, one of the physiological sensors is a
pressure transducer that is used to generate a signal indicative of
pressure in the left atrial chamber of the patient's heart (the
"left atrial pressure," or LAP). In one embodiment, a LAP versus
time signal is processed to obtain one or more medically useful
parameters. These parameters include, but are not limited to, mean
LAP, temporally filtered LAP (including low-pass, high-pass, or
band-pass filtering), heart rate, respiratory variations of LAP,
respiration rate, and parameters related to specific features of
the LAP waveform such as the so-called a, v, and c waves, and the
x, x', and y descents. All these parameters are well known to those
skilled in the art. Examples of such features in normal cardiac
pressure tracings are illustrated in FIG. 18. Examples of
parameters derived from specific LAP waveform features include the
mechanical A-V delay interval, as defined below (as distinct from
the electrical A-V interval derived from the electrocardiogram);
the relative peak pressures of the a and v waves, normal values of
which are given in the table in FIG. 19; and the pressure values at
specific times in the LAP waveform, as are understood by those
skilled in the art.
[0189] In one embodiment, signals indicative of left atrial
pressure are periodic signals that repeat with a period the length
of which is equal to the period in between heartbeats. Any portion
of the signal or a summary statistic of that periodic signal may be
indicative of left atrial pressure and provide diagnostic
information about the state of the heart. For example, the a, c, v
waves and the x, x', and y descents, described above, correlate
with mechanical events such as heart valves closing and opening.
Any one of these elements can yield useful information about the
heart's condition. Each discrete element represents an individual
signal indicative of left atrial pressure. A summary statistic such
as the arithmetic mean left atrial pressure also represents a
signal indicative of left atrial pressure. One skilled in the art
will appreciate that there are additional discrete elements and
summary statistics that are valuable indicators of left atrial
pressure. Advantageously these components of left atrial pressure
are relative to each other and therefore do not have to be
compensated for atmospheric pressure and are not subject to offset
drift inherent in most pressure transducers.
[0190] In one embodiment, the relative heights and/or shapes of the
left atrial "a," "c," and "v" waves are monitored to detect and
diagnose changes in severity of cardiovascular disease. This
information permits differentiation between worsening symptoms of
CHF due to volume overload versus impaired left ventricular pump
function (such as decrease left ventricular compliance, or acute
mitral regurgitation), allowing medical therapy to be appropriately
targeted. For example, pure volume overload is usually manifest
with a progressive elevation of the mean left atrial pressure and
generally responds to fluid removal by taking a diuretic
medication, natriuretic peptide, or and invasive technique known as
ultrafiltration of the blood. Decreased left ventricular compliance
is the diagnosis when the "a" wave increases without shortening of
the atrioventricular (AV) delay or in the presence of mitral
stenosis. Acutely decreased compliance may be indicative of left
ventricular (LV) ischemia, while chronically decreased compliance
may be indicative of LV wall thickening know as hypertrophy. The
former may respond to nitrates or coronary artery interventions,
while the latter may respond to beta or calcium antagonist drugs,
or chemical septal ablation. Increases in the "v" wave amplitude
and merging with the "c" wave to produce a "cv" wave is usually
indicative of acute mitral valve regurgitation. This may be due to
a sudden mechanical failure of the valve or its supporting
apparatus, or it may be due to acute ischemia of the supporting
papillary muscles as part of an acute coronary artery syndrome.
Sudden mechanical failure requires surgical repair or replacement,
while ischemia may require anti-ischemic medications such as
nitroglycerin or coronary artery interventions such as angioplasty
or bypass surgery. FIGS. 6A-6C list these and other parameters
derivable from cardiac pressure tracings that may be interpreted to
facilitate diagnosis of cardiovascular disease states.
[0191] In another embodiment, atrial fibrillation and atrial
flutter are detected by analysis of the LAP waveform. In another
embodiment, spectral analysis of the LAP versus time signal is
performed.
[0192] i. Measurement of Absolute Pressure
[0193] In one embodiment, an apparatus for measuring absolute
pressure at a location within the body is provided. In one
embodiment, the apparatus includes a transducer/communications
module for making measurements, and communicating the measurement
to another device, as described above. The
transducer/communications module can include transducers or sensors
suitable for measuring pressure, as are well known to those of
skill in the art, temperature, or other physiological parameters.
In one embodiment, the transducer/communications module measures an
absolute pressure. In another embodiment, the
transducer/communications module measures the pressure difference
between a location in the body and a reference pressure within the
implanted transducer/communications module.
[0194] ii. Measurement of Relative Pressure (Gauge Pressure)
[0195] In one embodiment, the system contains the necessary
components to obtain a signal indicative of pressure relative to
atmospheric pressure. An implanted apparatus for measuring absolute
pressure at a location within the body is provided as above, which
further communicates this information, as either an analog or
digital signal, to an external signal analyzer/communications
device. The external signal analyzer/communications device further
contains a second pressure transducer configured to measure the
atmospheric (barometric) pressure. The analyzer/communications
device performs a calculation using the absolute pressure from the
implanted module and the atmospheric pressure to obtain the
internal pressure relative to atmospheric pressure, that is,
difference between the absolute pressure at the location within the
body and the absolute barometric pressure outside the body. This
pressure, also known as the gauge pressure, is known to those
skilled in the art to be the most physiologically relevant pressure
measure. The implanted module may contain an internal power source
such as a battery, or it can be powered transcutaneously by
induction of radio frequency current in an implanted wire coil
connected to the module to charge an internal power storage device
such as a capacitor.
[0196] In one embodiment, gauge pressure measurements are performed
only when the implanted apparatus is queried by the external
analyzer/communications device, advantageously assuring that the
atmospheric pressure at the time and patient's location is
available and correctly matched with the absolute internal pressure
reading. It will be clear to those skilled in the art that
unmatched internal and barometric pressure readings would render
the gauge pressure measurement inaccurate or useless. In this
embodiment, internal absolute measurements are made only when the
external analyzer/communications device is physically present. In
one embodiment, this is accomplished by having the external device
supply operating power to the implant module to make the
measurement. In another embodiment, this is accomplished by
requiring a proximity RF link to be present between the external
and implantable modules, either immediately before and/or after
and/or during the measurement.
[0197] Other arrangements of pressure transducers will be apparent
to one skilled in the art. The transducer/communications module may
contain other types of sensing apparatus. In one embodiment, in
addition to the implanted pressure sensor, electrocardiographic and
temperature sensors are provided.
[0198] iii. Measurement of Differential Pressure
[0199] In another embodiment, an apparatus for measuring
differential pressure is provided. In one embodiment, the apparatus
includes a transducer/communications module for making
measurements, and communicating the measurement to another device,
such as a processor, or patient advisory module. The
transducer/communications module can include transducers or sensors
(these terms are used synonymously herein), suitable for measuring
pressure as are well known to those of skill in the art,
temperature, or other physiological parameters. In one embodiment,
the transducer/communications module measures a differential
pressure that includes the pressure difference between two
locations inside of the body. For example, the
transducer/communications module measures the difference between
the fluid pressure of the blood in an artery, and the intrathoracic
pressure, detected through the artery's wall. In another example,
the transducer/communications module measures the difference
between the fluid pressure in the left atrium and the left atrium
of the heart, detected by a module
[0200] In one embodiment, the transducer/communications module
includes a plurality of pressure sensing membranes, each with an
outer surface and an inner surface. In one embodiment, there are
two pressure sensing membranes in the module so that when the
device is implanted, for example in the atrial septum, one pressure
sensing membrane's outer surface is in contact with the blood of
the left atrium and the other pressure sensing membrane's surface
is in contact with the blood of the right atrium. The inner
surfaces of both pressure-sensing membranes are exposed to the same
internal space within the device. Each membrane has an associated
strain gauge, each strain gauge creating a signal indicative of the
pressure difference between the outer and the inner surfaces of the
respective membrane. Since the two membranes share the internal
space, the pressures on their inner surfaces are equal. Thus, the
differential pressure, determined by subtracting the pressure of
one transducer from the other, is proportional to the left atrial
pressure in reference to the right atrial pressure. The
baseline-offset calibration of the differential transducer can be
determined by having the patient perform a Valsalva maneuver, which
is known by those skilled in physiology to equalize the pressure
within the chambers of the heart.
[0201] In one embodiment, the module contains the necessary
components to obtain from the transducers a signal indicative of
differential pressure, and to communicate this information either
as an analog or digital signal, indicative of the severity of a
condition, such as congestive heart failure, to an external signal
analyzer/communications device. The implanted module may contain an
internal power source such as a battery, or it can be powered
transcutaneously by induction of radio frequency current in an
implanted wire coil connected to the module to charge an internal
power storage device such as a capacitor.
[0202] b. Other Measures Indicative of Left Atrial Pressure
[0203] In one embodiment, pulmonary artery diastolic pressure
(PADP) is estimated from an analysis of the right ventricular
pressure waveform, as taught by Carney in U.S. Pat. No. 5,368,040,
incorporated by reference in its entirety herein. In one
embodiment, the pressure module is placed in the right ventricle.
In other embodiments, the pressure module is placed in the right
atrium or a pulmonary artery. It is known to those skilled in the
art that under certain circumstances, PADP approximates the
pulmonary capillary wedge pressure (PCWP), which is a clinically
useful measure of mean left atrial pressure. In this case, the
right ventricular pressure waveform provides a signal indicative of
left atrial pressure.
[0204] In several embodiments, non-pressure physiologic signals are
used to indicate left atrial pressure. In most cases, these
non-pressure physiologic signals correlate to left atrial pressure
through straightforward mathematical relationships. For example,
for periodic signals of left atrial pressure and volume, a periodic
pressure-volume relationship may be used. One well-known example of
a pressure-volume relationship occurs during atrial diastole, when
the ratio .DELTA.V/.DELTA.P, known as the diastolic compliance, is
generally stable. Thus, a given left atrial volume, cross-sectional
area or any dimension indicative of that volume is also a signal
indicative of left atrial pressure, and a sensor capable of
measuring a left atrial dimension or area may be used to determine
left atrial pressure. Thus, in one embodiment of the invention, one
or more physiological sensors are provided to directly or
indirectly sense one or more of the following physiological
parameters: left atrial dimension, cross-sectional area, and/or
volume; left ventricular dimension, cross-sectional area or volume;
atrial septum position; heart chamber wall velocity, and/or
acceleration.
[0205] Examples of sensors capable of measuring such dimensions or
areas include, but are not limited to an intracardiac ultrasonic
imaging system operating in M-mode, 2-dimensional, or 3-dimensional
modes, as well as paired ultrasonic crystals. It is well known in
the art that heart chamber dimensions or cross-sectional areas may
be measured and volumes estimated by the use of ultrasound, as
described, for example, by Kojima (U.S. Pat. No. 4,109,644) and by
Hemmingsson (U.S. Pat. No. 6,421,565), both incorporated by
reference herein. Such ultrasonic systems may have additional
diagnostic value in that Doppler analysis can detect changes in
atrial flow patterns due, for example, to mitral regurgitation.
[0206] It is also known in the art that electrical impedance
changes may be indicative of changes in heart chamber dimensions.
An example of a physiological sensor suitable for use in one
embodiment of the current invention is described by Alt (U.S. Pat.
No. 5,003,976), incorporated by reference herein. Alt describes how
analyzing the impedance between two intracardiac electrodes may be
used to determine changes in cardiac chamber volumes, which under
certain circumstances as described above are indicative of changes
in chamber pressures, and thus may be used to detect worsening
heart failure and guide therapy according to the present
invention.
[0207] In accordance with the above description, an embodiment of
the present invention comprises a physiologic signal detection
sensors set which may be alternately described as:
[0208] {S.sub.iLAV, S.sub.2, . . . S.sub.n}, where S.sub.iLAV is a
sensor indicative of left atrial volume;
[0209] {S.sub.iLAA, S.sub.2, . . . S.sub.n}, where S.sub.iLAA is a
sensor indicative of left atrial cross-sectional area; or
[0210] {S.sub.iLAD, S.sub.2, . . . S.sub.n}, where S.sub.iLAD is a
sensor indicative of left atrial dimension;
where the first sensor in all sets detects a signal that is
indicative of left atrial pressure. Additional sensors in the
implanted portion of the device may include detectors for any other
physiologic signal. For example:
[0211] {S.sub.iLAP, S.sub.iLAD, S.sub.iECG, S.sub.iCT, S.sub.iO2, .
. . S.sub.n},
where sensors denoted by subscripts iECG, iCT, iO.sub.2 are
detectors or signals indicative of the electrogram, core
temperature, and oxygen saturation, respectively. One skilled in
the art will appreciate that there are numerous sensor
configurations and sensor types that may be used in accordance with
various embodiment of the present invention.
[0212] In one embodiment of the invention, multiple physiologic
sensors are contained in a single package. In another embodiment, a
plurality of packages is spatially distributed. Some of the
packaging may place a particular sensor outside of the body. For
example, in one embodiment, signal detection sensor packages
P.sub.1, P.sub.2, and P.sub.3 may be located internally or external
to the body and consist of the following sets:
[0213] P.sub.1={S.sub.iLAP, S.sub.iCT}, located in the intra-atrial
septum;
[0214] P.sub.2={S.sub.iECG}, located in the superior vena cava;
and
[0215] P.sub.3={S.sub.iABP}, where iABP is a signal indicative of
arterial blood pressure.
[0216] One skilled in the art will appreciate that several
embodiments of the current invention include the detection of
various signals indicative of left atrial pressure. Such signals
include, but are not limited to: a, c, v, x, x', and y of LAP, mean
LAP, the respiratory portion of LAP, the total cardiac portion of
LAP, and filtered LAP between frequencies. In several embodiments,
non-LAP signals are used. These non-LAP signals include, but are
not limited to, the detection of a and b left atrial volume, left
ventricular volume, atrial fibrillation, atrial flutter,
respiratory tidal volume, respiratory rate, weight change, blood
pressure or change in blood pressure, core temperature, oxygen
saturation, oxygen partial pressure, cardiac output, LA to RA
temperature differential, lung acoustic signal, and EEG.
[0217] One skilled in the art will understand that numerous
configurations of sensors and sensor packaging and locations may be
used in accordance with various embodiments of the current
invention.
[0218] c. Other Blood Pressure Signals
[0219] In another embodiment, one or more physiological sensors
measure central venous blood pressure.
[0220] In one embodiment of the invention, one or more of the
physiological sensors measure peripheral arterial blood pressure.
Analysis of peripheral artery blood pressure to obtain a parameter
indicative of congestive heart failure status has been described,
by Finkelstein (U.S. Pat. No. 4,899,758), incorporated by reference
herein. In one such embodiment, the peripheral artery blood
pressure sensor may be a cuff sphygmomanometer, and the patient's
systolic and diastolic blood pressures are entered into the signal
processing apparatus by the user. In a further embodiment, the
blood pressures may be sent by direct signal communication to the
signal processor.
[0221] d. Other Physiological Parameters
[0222] In one embodiment, the internal electrocardiogram (known as
the IEGM) is sensed at one or more locations. In a further
embodiment, the IEGM is processed to obtain one or more medically
useful parameters. These parameters include, but are not limited
to, heart rate, the timing of atrial and ventricular
depolarization, the time interval between atrial and ventricular
depolarization (known in the art as the A-V interval), the duration
of ventricular depolarization (known in the art as the Q-T
interval), ST segment changes to detect acute ischemia, and
spectral analysis to detect t-wave alternans (a known harbinger of
life threatening arrhythmias), all of which are familiar to those
skilled in the art.
[0223] In one embodiment, one of the physiological sensors is a
thermometer measuring core body temperature, as described
above.
[0224] In one embodiment of the present invention, Doppler
ultrasound provides a signal that is proportional to the relative
velocity of the ultrasound probe and a structure, such as a heart
chamber wall, producing an ultrasound echo. A velocity signal can
be differentiated to obtain an acceleration, as is well known to
those skilled in the art. Conversely, implantable accelerometers
are sensors known in the art that provide a signal that is
proportional to the acceleration of the implanted sensor. An
acceleration signal can be integrated to obtain a velocity plus an
arbitrary constant velocity. Because it is known that the average
velocity of any structure in the body, relative to the body, is
necessarily zero, the arbitrary constant velocity is determined,
and the relative velocity signal can be uniquely recovered from the
acceleration signal. Thus, velocity and acceleration measurements
of structures in the heart are essentially equivalent, the one
being derivable from the other. As is well known in the art, a
velocity signal may be integrated to obtain a position or
displacement signal plus an arbitrary constant displacement. Thus,
the motion and displacement of a structure in the heart, or the
range of variation of the dimension of a chamber of the heart, may
be recovered from the velocity or acceleration signal of the
structure or of the chamber walls, respectively.
[0225] Vallana and Garberoclio (U.S. Pat. No. 5,454,838,
incorporated by reference herein) teach that components of the
velocity or acceleration signal are indicative of aspects of
cardiac activity, such as opening of the mitral valve, closure of
the mitral valve, opening of the aortic valve, closure of the
aortic valve, an amount of ventricular ejection, rapid ventricular
filling, delayed ventricular filling during atrial systole, and
cardiac flow rate. As these aspects of cardiac activity may be
indicative of changes in the patient's condition, and may be
responsive to changes in the patient's prescription, they are
within the scope of parameters contemplated to be used with
embodiments of the present invention.
[0226] In another embodiment of the present invention, a
physiological sensor measures respiratory tidal volume, respiratory
rate, lung acoustic signal, and/or thoracic electrical
impedance.
[0227] In one embodiment of the invention, one of the physiological
sensors measures total body weight. In one embodiment, the sensor
is a scale. In another embodiment, the patient's weight is entered
into the signal processing apparatus by the user. In another
embodiment, the weight sensor is a scale that communicates a signal
indicative of the patient's weight to the signal processing
apparatus without requiring a user to enter the value. Lloyd et al.
(U.S. Pat. No. 6,080,106), incorporated by reference herein,
describe a digital scale suitable for use in one embodiment of this
invention.
[0228] In yet another embodiment of the invention, one or more
sensors measure: oxygen saturation; oxygen partial pressure in the
left, right, both left and right-sided cardiac chambers, or
adjacent great blood vessels; or cardiac output.
[0229] 5. Signal Processing Apparatus
[0230] In one embodiment, the signal processing apparatus of the
present invention receives signals from the one or more sensors,
and processes them together with stored parameters relevant to the
patient's medical management. In one embodiment, the result of this
processing is a signal indicative of the appropriate therapeutic
treatment or course of action the patient or an immediate personal
care giver can take to manage or correct, as much as possible, the
patient's condition. In one embodiment, the signal processing
apparatus is located outside the patient's body. In one embodiment,
signals from one or more permanently implanted physiological
sensors are received by the external signal processing apparatus by
wireless telemetry. In one embodiment, certain signal processing is
performed within the one or more individual sensor devices prior to
the signal being sent to the signal processing apparatus. In one
embodiment one signal received by the signal processing apparatus
is the LAP versus time waveform sampled at over 20 Hz for a
duration of several respiratory cycles (for example, but not
limited to, 10 to 30 seconds). In one embodiment, the signal
processing apparatus also receives a signal from a temperature
sensor located at substantially the same position as the LAP sensor
and uses this temperature to apply a temperature compensation
correction to the LAP signal using calibration data stored in the
signal processing apparatus. In one embodiment, the processor also
receives ambient temperature and atmospheric pressure, performs
temperature compensation, and subtracts the atmospheric pressure
from the LAP to obtain the relative or "gauge" LAP. In one
embodiment, the signal processing apparatus then computes the mean
LAP from the relative LAP versus time waveform. In one embodiment
the signal processing apparatus then compares the mean LAP with
patient-specific treatment ranges for mean LAP that have been
programmed into the signal processing apparatus by the patient's
physician. In one embodiment, for each patient-specific programmed
treatment range the patient's physician stores in the signal
processing apparatus an indication of the appropriate therapeutic
treatment or action the patient should take to manage or correct,
as much as possible, the patient's condition. A signal indicative
of the physician-prescribed therapeutic action corresponding to the
patient-specific range into which the measured physiologic
parameter falls is then sent to a patient signaling device.
[0231] In another embodiment of the invention, the signal
processing apparatus is essentially permanently implanted within
the body, in either the same or a different location as the one or
more physiological sensors. In one embodiment, the sensors may be
in signal communication with the signal processing apparatus by
means of one or more connective leads that may carry electrical,
optical, hydraulic, ultrasonic or other forms of signaling energy.
The conductive lead(s) may vary in length up to and exceeding about
100 cm. In another embodiment, the sensors may be in wireless
communication with the signal processing apparatus. The lead can be
coupled to an antenna for wireless transmission or to additional
implanted signal processing or storage apparatus.
[0232] 6. Interpretation of Signals
[0233] In one embodiment of the present invention, patients are
diagnosed based upon the interpretation of signals generated by one
or more sensors. For example, a signal indicating low mean right
atrial pressure may suggest hypovolemia or improper zeroing of the
transducer. FIGS. 6A-6C provide other examples by which signals may
be interpreted to facilitate diagnosis, prevention and treatment of
cardiovascular disease according to various embodiments of the
present invention.
[0234] One skilled in the art will understand that other
interpretations may be used in accordance with various embodiments
of the current invention. Further, one skilled in the art will
understand that normal ranges of the various physiologic parameters
measured in several embodiments of the current invention can be
found in any cardiology textbook or reference book. Additionally,
it may be useful to compare patient parameters within the same
patient by ascertaining initial baseline values and comparing these
baseline numbers to values generated at some later desired time.
This may be particularly useful in determining progression of
disease and response to treatment.
[0235] In several embodiments, sensors in addition to the left
atrial pressure sensor are used. Additional sensors provide further
refined diagnostic modes capable of distinguishing between
different potential causes of worsening cardiovascular illness, and
then of signaling an appropriate therapeutic treatment depending
upon the particular cause for any particular occurrence.
[0236] For example, increased left atrial pressure is commonly
caused by improper administration of medication, patient
non-compliance, or dietary indiscretion, e.g., salt binging. These
causes will be generally well-handled by changes in the patient's
drug regimen like those described above. However, there are other
causes of increased left atrial pressure that are less common, but
by no means rare, and which require different therapies for
adequate treatment. For example, one such potential cause is
cardiac arrhythmia, and especially atrial fibrillation with a rapid
ventricular response. Other arrhythmias may contribute as well to
worsening heart failure. A system including an ECG electrode in
addition to the left atrial pressure sensor would allow the system
to diagnose arrhythmias and determine whether the arrhythmia
preceded or came after the increase in left atrial pressure.
Depending on the unit's programming, as specified by the patient's
physician, specific therapies could be signaled tailored to treat
the specific causes and conditions associated with particular
adverse events.
[0237] In another example of the usefulness of additional
physiological signals is to distinguish between pulmonary
congestion caused by worsening CHF and that caused by a respiratory
infection. In a further embodiment, core body temperature is used
together with left atrial pressure to allow the early detection of
fever associated with infection. It is well known that core body
temperature often becomes elevated hours to days prior to
symptomatic fever associated with infection-related pulmonary
congestion. In one embodiment, increased core temperature in the
presence of stable left atrial pressure would trigger a message to
the patient not to increase the dosage of oral diuretic despite
symptoms of increasing congestion, and to consult with the
physician.
[0238] 7. Patient Signaling Devices
[0239] In one embodiment, the signal processing apparatus and the
patient signaling device are permanently implanted, and the patient
is signaled using at least two distinguishable stimuli, such as
distinguishable sequences of vibrations, acoustic signals, or mild
electrical shocks, perceptible by the patient.
[0240] According to one embodiment of the invention, one or more
physiological sensors is implanted within the body, the signal
processing apparatus and the patient signaling device are located
outside the body, and the signal indicative of a physiological
parameter is communicated by wireless telemetry through the
patient's skin. In one embodiment, an external telemetry system is
combined with the signal processing apparatus and the patient
signaling device. In one embodiment, a hand-held personal data
assistant (PDA) such as the Palm Pilot or Handspring Visor is used
for the signal processing and patient signaling apparatus. In one
embodiment, patient signaling is accomplished using sound, text,
and/or images.
B. Combination with Other Devices
[0241] It will be clear to those skilled in the art that many
patients who would benefit from several embodiments of the present
invention would also benefit from an implantable CRM apparatus such
as a cardiac pacemaker. In one embodiment, the present invention is
combined with an implantable CRM apparatus generator. In one
embodiment, the flexible lead on which the physiological sensor is
disposed also serves as the sensing or pacing lead of an
implantable rhythm management apparatus. In this case, conductors
within the lead provide for EKG sensing, powering of the
physiological sensor, data communication for the physiological
sensor, and pacing stimulus.
[0242] In another embodiment, the present invention is functionally
integrated with another implantable device, such as, for example, a
pacemaker or a defibrillator. In one embodiment of this invention,
one or more parameters indicative of a physiological condition
produced by the present invention are used by the integrated device
to control its therapeutic function, as described below.
[0243] In yet another embodiment, the sensor and lead of the
Stand-Alone device may be connected without modification either to
a subcutaneous coil antenna as described above, or to a combination
CRM generator housing containing a battery power supply and other
components as described below. In one embodiment the device may be
upgraded after permanent implantation by replacing the coil antenna
assembly with an implantable CRM apparatus.
[0244] 1. Combination with Cardiac Rhythm Management (CRM)
Apparatus
[0245] Many patients who might benefit from several embodiments of
the present invention described above would also be likely to
benefit from an implantable CRM apparatus for therapy of brady- or
tachy-arrhythmia in the setting of CHF. Examples of such CRM
devices include single or multichamber cardiac pacemakers;
automatic implanted cardiac defibrillators; combined
pacemaker/defibrillators; biventricular pacemakers; and
three-chamber pacemakers, all well known to those skilled in the
art. In these patients, it would be beneficial to combine several
embodiments of the present invention with such a CRM device. This
combination would have the advantage that certain components of
both systems could be shared, reducing cost, simplifying
implantation, minimizing the number of implanted devices or leads.
As described in detail below, in some embodiments a combination
with a CRM apparatus includes adding pacing and/or defibrillation
to the therapeutic actions included in the dynamic prescription of
several embodiments of the present invention.
[0246] In one embodiment, a flexible lead serves also as an atrial
septal pacing lead. It will be recognized by those skilled in the
art, such as cardiologists, that pacing the atrial septum provides
certain advantages for patients with congestive heart failure.
These advantages may include more direct control over left
atrial/left ventricular synchrony, inhibition of atrial
fibrillation, and it requires one less lead to be inserted in
patients that are in need of a rhythm management device that
includes atrial pacing and a hemodynamic monitoring/therapy device,
etc.
[0247] It will also be known to those skilled in the art that
pacing multichamber sites in appropriate sequence in addition to
the atria, such as the right ventricle and the lateral wall of the
left ventricle in combination, or the lateral wall of the left
ventricle alone, has specific advantages for some patients with
congestive heart failure. FIG. 20 illustrates one embodiment of the
present invention in which a sensor package 15 at the end of
flexible lead 10 is implanted across the atrial septum 41 of a
patient's heart 33. The sensor package 15 measures the left atrial
pressure and also serves as the atrial septal pacing electrode of a
CRM device, which may be located within an implanted housing 7. A
second flexible lead 160 is placed via the right atrium 30 into the
right ventricle 37. Each lead is shown with an indifferent
electrode 14 proximal to its respective distal electrode, although
those skilled in the art will recognize one of these could be
eliminated. The housing 7 contains the CRM device (not shown),
which in one embodiment includes a battery and electrical circuitry
for pacing the heart 33, and components of physiological monitoring
system. It will be clear to the skilled artisan that a variety of
configurations may be used to combine the CRM and physiological
monitoring functions of such a combined device, examples of which
are described below.
[0248] In one embodiment, the housing 7 includes a coil antenna 161
for communicating the one or more physiological signals from sensor
package 15 to an external patient advisory module 6. In one
embodiment, the external patient advisory module 6 includes a
telemetry module 164 and antenna 162, a barometer 165 for measuring
atmospheric pressure, and a signal processing/patient signaling
device 166, such as described above with reference to FIG. 5.
[0249] In one embodiment, components are housed within the
implantable housing of an implantable CRM apparatus, including but
not limited to the power source, signal processing apparatus,
telemetry apparatus, or patient alarm. Alternatively, in another
embodiment, components of a CRM may be shared with other
implantable devices, such as the apparatus for treating congestive
heart failure described in greater above. Components that may be
shared include, but are not limited to, a power source, telemetry
module, data memory, etc. For example, the flexible physiological
sensing lead of any of the apparatus for treating congestive heart
failure described above may be use as a pacing lead of a CRM. In
other embodiments, separate pacemaker and sensing leads are
provided.
[0250] In one embodiment of the present invention, components of
the apparatus for treating congestive heart failure are shared with
the components of a CRM apparatus in such a way that, while sharing
components, the two systems function essentially independently. In
one embodiment, the implantable CRM apparatus generator has a
housing that also serves as the housing for at least some
components of the apparatus described in greater detail above. In a
further embodiment, the power supply of the CRM apparatus,
typically comprising a long lifetime battery and power management
circuitry, also supplies power for one or more components of the
apparatus for treating congestive heart failure. In yet another
embodiment, the flexible lead or leads connecting the sensors of
the apparatus of FIG. 1, FIG. 2, and FIG. 4, to a shared
housing/generator are also coupled to sensing and/or pacing
electrodes of the CRM apparatus.
[0251] In one embodiment, one or more separate leads coupled to the
physiological sensor described above, such as a pressure
transducer, is also coupled to the CRM apparatus. In this
embodiment, the CRM apparatus shares its generator housing with
components of the implantable heart monitor apparatus described
above, but the CRM apparatus leads are separate from the
physiological sensor leads. In another embodiment, the pressure
sensing lead may be combined with a pacing lead, as described for
example by Pohndorf (U.S. Pat. No. 4,967,755) or Lubin (U.S. Pat.
No. 5,324,326), herein incorporated by reference.
[0252] a. Integration of Sensor and Pacing Lead
[0253] In one embodiment of the present invention, a system and
method is provided for combining a CRM apparatus, implantable heart
monitor, and patient communication device. The system provides the
following functionality via a single pacing/sensing lead which in
one embodiment includes only two conductors: (1) provides power to
the physiological measurement module(s); (2) provides signaling for
atrial pacing and sensing; (3) provides for programming of the
physiological sensor package(s); and (4) provides measurement data
from the physiological sensor package(s) to the
monitor/defibrillator housing for immediate or delayed use by the
patient, doctor or other caregiver via the patient signaling
module. Additional pacing and/or sensing leads may be added.
[0254] In one embodiment, an external telemetry device (such as
described above with reference to FIG. 4 and FIG. 5) is used to
communicate with and query a CRM/heart monitor system. The external
device analyzes the data with respect to the doctor's prescription,
and then indicates to the patient which and what dose of
medications or other actions he or she should take. In one
embodiment, the data is also provided to the logic within the CRM
system for improving pacing or defibrillation therapy.
[0255] For example, in one embodiment, the pressure waveform from
the left atrial chamber contains information pertinent to adjusting
atrioventricular dual chamber or atrio-biventricular triple chamber
pacing for optimizing the synchrony between left atrial and left
ventricular mechanical contraction. FIG. 21 shows why it is
difficult for pacemakers to automatically control the optimal delay
between the left atrium (LA) and left ventricle (LV). The
electrical atrioventricular delay (AV delay), which a conventional
CRM system can sense, may be substantially different that the
mechanical AV delay, which the conventional CRM cannot sense, but
which is the relevant interval for optimizing cardiac function. The
relationship between the electrical AV delay and the mechanical AV
delay is dependent on several, difficult to measure variables,
including intra-atrial conduction time, sub-AV node/HIS bundle
conduction delays, volume/pressure preloading of the atria and
ventricles and ventricular contractility, among other things, as is
known to cardiologists and electrophysiologists. The mechanical AV
delay is clinically important because if the delay is too long,
usually greater than about 250 msec, then atrial contraction does
not have an effective pressure boosting/volume priming effect on
the left ventricle, thus adversely effecting LV contractility,
stroke volume, and cardiac output. If the mechanical AV delay is
too short, usually less than about 120 msec, atrial contraction
occurs against a closed or closing mitral valve, again adversely
affecting atrial emptying, and pressure/volume boosting of the LV
pump. Both a too long and a too short LA-LV mechanical delay can
potentially worsen heart failure by further raising the LA
pressure. These conditions are potentially extractable from an LA
pressure tracing in the following ways. Too long an LA-LV
mechanical delay will manifest as an increase in the amplitude of
the LA pressure "v" wave relative to the "a" wave and an
exaggeration of the "x" descent. Too short an LA-LV mechanical
delay will manifest as an increase in the LA pressure "a" wave
relative to the "v" wave and a reduction in the "x" descent. As
illustrated in FIG. 21, the actual mechanical LA-LV delay can be
directly measured from the LA pressure waveform as the interval
from the onset of LA contraction represent by the LA pressure "a"
wave, to mitral valve closure represented by the "c" wave. In one
embodiment, the measured mechanical AV delay is used to adjust the
electrical AV delay by a feedback control system or an algorithm to
achieve a preset ideal AV delay, or alternatively by minimizing LA
mean pressure.
[0256] There are other features in the LA pressure waveform that
can be used to modify pacing parameters such as backup atrial
pacing rate and rate-responsive algorithms that will be apparent to
one skilled in the art. For example, to increase cardiac output,
and potentially lower the left atrial pressure, the resting heart
rate may be raised from the typical backup atrial pacing rate in
the range of 60 to 70 beats per minute when the patient is in
compensated heart failure (mean LAP<16-20 mm Hg), to a faster
backup atrial rate when the patient is decompensated with an
elevation of LAP. Similarly, the mean left atrial pressure can be
used to modify rate response algorithms, normally based on
activity, minute ventilation, or other physiologic parameters, so
that the rate response is also specific to the state of congestive
heart failure.
[0257] In another embodiment, the signal processor, dynamic
prescription, and patient signaling device are completely contained
within the implanted CRM apparatus housing. Several methods of
patient signaling from an implanted device are well known in the
art, including the use of mild electrical stimulation (e.g., U.S.
Pat. Nos. 4,140,131, 4,619,653 and 5,076,272), or audible sounds
(e.g., U.S. Pat. Nos. 4,345,603 and 4,488,555), including
intelligible speech (e.g., U.S. Pat. No. 6,247,474), all herein
incorporated by reference.
[0258] In another embodiment, the measurement of pressure or other
physiological parameters may be multiplexed with the pacing signal
(as described in greater detail below) so that pressure sensing and
telemetry would occur between pacing signals, for example as taught
by Barcel (U.S. Pat. No. 5,275,171) or Weijand et al. (U.S. Pat.
No. 5,843,135), both incorporated by reference herein.
[0259] In one embodiment, pressure sensor electronics are
integrated within a miniature hermetically sealed sensor package
implanted in the heart, minimizing the number of conductors
required in the lead between the sensor and the CRM apparatus
generator housing. In this embodiment, the pressure sensor lead may
also be used for pacing, with the sensor package, or portion
thereof, used to include one of the electrodes of the CRM
apparatus. In addition, in one embodiment, some of the pacing
electronics are integrated within the sensor package that is
implanted within the heart. This has the advantage that the lead
conductors are isolated from the pacing electrode, providing
immunity from induced currents when, for example, the patient is
placed in the rapidly changing strong magnetic fields of a magnetic
resonance imaging machine.
[0260] In clinical use, conventional cardiac pacemakersuse analog
voltages on the lead between the pacemaker generator and the heart
for pacing, sensing and physiological measurements. As such, the
sensing signals in particular are subject to noise due to muscular
activity, radio frequency (RF) interference, and potential
cross-talk between physiological and electrical sensing signals.
Lead conductors carrying analog signals act as antennas for RF
noise and for induced voltages due to RF energy used in magnetic
resonance imaging (MRI) scanners. RF noise on a sense conductor may
cause erroneous pacing, even with sophisticated filtering
algorithms that are commonly used in pacemaker sensing systems.
Voltages induced by RF and changing magnetic fields are a primary
reason why MRI scanning is contraindicated for patients with
implantable cardiac pacemakers.
[0261] In one embodiment, a pacemaker is provided in which the
electronics for producing the pacing pulse output and for sensing
the ECG are integrated within a sensor package at the site of the
pacing electrode, which is generally implanted within the heart.
This allows the lead conductors to be substantially isolated from
the pacing electrode, thereby providing increased immunity from
induced currents when, for example, the patient is placed in the
rapidly changing, strong magnetic fields of a magnetic resonance
imaging machine. The lead may incorporate one or more sensors
without requiring additional lead conductors.
[0262] In one embodiment, the electronics in the proximal housing,
for example, a housing implanted near the shoulder, operate at
lower voltage than voltages required for pacing, and as a result
are fabricated using smaller feature size CMOS technology. This
allows for a smaller package and lower power consumption. The
distal pacemaker components, for example, those located in the
heart, are fabricated using larger feature size CMOS technology to
handle the higher pacing voltage.
[0263] In one embodiment, the system allows sensing signals to be
processed within the heart, thereby eliminating the risk of picking
up noise with lead conductors. Separate sensing and pacing
electrodes may be provided, with no additional lead conductors.
This allows the sensing and pacing electrodes to be individually
optimized. Pacing electrodes are optimally small in area to
minimize required voltage for pacing, while sensing electrodes are
optimally of large area to minimize impedance.
[0264] Referring now to FIG. 22 and FIG. 23, two embodiments of a
sensor package 200 are shown in which separate electrodes for
sensing 202 and pacing 204 are included. In the embodiment of FIG.
22, the sensing electrode 202 is located at the proximal portion or
segment 208 of the sensor package 200, while the pacing electrode
204 is located at the package distal portion or segment 210. The
sensing and pacing electrodes 202, 204 are electrically separated
by an insulating segment or ring 206. In one embodiment the
insulating ring 206 is a cylindrical ceramic segment to which
metallic proximal and distal segments 208, 210 of the sensor
package 200 are hermetically fastened. Hermetic fastening may be
achieved by using methods that are well known to those skilled in
the art, such as, for example, braising.
[0265] In one embodiment, the surface area of the pacing electrode
204 is reduced by coating selected areas of the metallic distal
segment 210 with an insulating material. In one embodiment, the
insulating material is a tenacious thin coating such as, for
example, parylene. One or more selected small areas may be masked
off prior to coating to provide for one or more electrically
conducting pacing electrodes 204. In one embodiment, the pacing
electrode 204 includes an annular region 212. In another
embodiment, the pacing electrodes 204 include areas on the distal
anchor members 214 such that the pacing current is applied
preferentially to the left atrial wall of the septum. In one
embodiment, the pacing electrodes 204 include metallic electrodes
fastened to tips of one or more of the distal anchor members 214.
In one embodiment, the metallic tip electrodes are made of
tantalum, which has the desirable property that it can be made as a
porous, high surface area material. It will be familiar to the
skilled artisan that such materials reduce contact impedance with
tissue. Tantalum has the additional property of high x-ray density,
which allows the anchor tips to be visualized under fluoroscopy for
verifying the positioning and deployment of the anchor 214.
[0266] Referring now to FIG. 23, in another embodiment, two
insulating ceramic segments 216, 218 are provided, which divide the
sensor package housing 200 into distal, middle, and proximal
metallic segments 220, 222, and 224. In one embodiment, the distal
and proximal metal segments 220, 224 are substantially uncoated and
serve as a sensing electrode 202, while the middle metallic segment
222 includes the pacing electrode 204. In a further embodiment,
portions of the middle segment 204 are coated with a material such
as, for example, parylene, to produce one or more smaller area
pacing electrodes.
[0267] In one embodiment, the pacing and sensing electrodes 202,
204 of FIG. 22 and FIG. 23 are electrically coupled to pacing
electronics located within the sensor package 200. In another
embodiment, the sensor package pacing electronics are configured to
detect a specific electrical event within the heart, such as the
p-wave of the internal electrogram, as is well known to those
skilled in the art of electrophysiology, cardiology and cardiac
pacing. In one embodiment, the sensor package pacing electronics
are further configured to send a digital signal indicating a sensed
event, such as detection of the p-wave, to the pacing electronics
in the proximal housing, as described further below.
[0268] In one embodiment of the present invention, a defibrillator
and an implantable heart monitor (such as describe above with
reference to FIG. 1 through FIG. 5) are combined to provide the
following functionality via an essentially standard
pacing/defibrillator lead with only two conductors: (1) provide
power to a physiologically optimized dosimeter (POD) measurement
module(s); (2) provide signaling for atrial and/or ventricular
pacing and sensing, (3) provide for atrial and/or ventricular
defibrillation through a third lead attached to a defibrillation
electrode; (4) provide for programming of the physiological sensor
package; and (5) provide measurement data from the physiological
sensor package(s) to the monitor/defibrillator housing for storage
and recovery by, e.g., a doctor or the patient via the patient
signaling module.
[0269] In one embodiment, digital signaling is used to provide for
power, two-way data communication, and pacing over a two-wire lead.
In one embodiment, digital signaling consists of dividing a "frame"
of a defined duration into a number of distinct sub-frame
intervals, each with a defined function, as shown in the pulse
timing diagram in FIG. 24. In one interval, a power pulse may be
provided to charge the power supply of the sensor/pacing module. In
one embodiment, the power pulse is provided during the first
interval of every frame, so that the power pulse defines the end of
one frame and the beginning of the next frame. In one embodiment,
power pulses are generated at a precisely timed frequency within
the generator module and this timing is used within the
sensor/pacing module(s) to adjust an internal RC or current source
clock for better synchronization between the distal sensor/pacing
module and the generator module at the proximal end of the lead.
Between one power pulse interval and the next, other intervals may
be defined as needed for the transmission of data and signals over
the lead. In one embodiment, the amplitude or magnitude of the
power pulse is the same as the amplitude or magnitude of the data
pulses, such as shown in FIG. 24. However, in other embodiments,
the amplitude or magnitude of the power pulse is greater than, or
less than the amplitude or magnitude of the data pulses. In one
embodiment, the amplitude of the power pulse does not vary between
pulses, and in another embodiment, the amplitude of the power pulse
varies between pulses, or within pulses.
[0270] In the embodiment described in FIG. 24, the next two
intervals are provided for signaling from the CRM module to the
sensor/pacing module(s). In one embodiment, these two intervals are
called the "download interval." The first interval is asserted by
the CRM module to command that a pacing stimulation pulse be
applied (e.g., A-pulse Trigger). The second interval is asserted by
the CRM module to indicate that commands producing a change in the
mode of operation of the sensor/pacing module are to follow (e.g.,
Programming Bit set). Following the download interval, an "upload
interval" may be provided for communication of information from the
sensor/pacing module back to the generator module. As shown in FIG.
24, this information may include a bit that, if asserted, indicates
an atrial and/or ventricular sensed event, and/or measurement data,
and/or status information about the current mode of operation of
the sensor/pacing module.
[0271] In one embodiment, the type of data following the A-sense
upload interval may be either upload or download data depending,
for example, on whether a programming or pacing command had been
asserted. In the embodiment of FIG. 24, if neither of the two
download bits has been asserted in the current or the previous
frame, the time intervals following the A-sense interval are used
by the sensor/pacing module to upload measured data, such as
pressure, temperature and electrogram (IEGM) waveform data. In
order to conserve power, the pressure, temperature and IEGM data
could be measured and output at a low duty cycle. If the
Programming Bit is asserted in the current frame, the sensor/pacing
module is set to listen for programming command bits sent by the
CRM module. If either the A-pulse trigger or the Programming Bit
was set in the previous frame, the sensor/pacer module provides
status information indicating whether the command was
successful.
[0272] In one embodiment, the download and upload intervals are
subdivided into data words, each containing a predefined number of
bits, so that multiple pieces of information are communicated. For
example, the download interval may consist of a pacing command
pulse followed by one or more programming bits. The upload interval
may consist of a sensing bit (set if P- or R-wave of internal
electrocardiogram is sensed by the measurement module), followed by
a predetermined number of bits of pressure data, followed by a
second predetermined number of bits of temperature data. All
signals, including pressure, IEGM, and temperature, may be
"alternated` in some fashion rather than being included in any
single frame, to allow for shorter frames and therefore more
frequent power supply support and synchronization. It will be clear
to one skilled in the art that data from additional sensors may be
appended in the same way. In one embodiment, additional checksum
bit(s) are added to guard against data transmission errors.
[0273] In one embodiment, the power and signaling pulses described
above are carried between the CRM module and the measurement
module(s) via a two-conductor lead. Each conductor is internally
connected within both modules. The first conductor may also be
attached to the "indifferent" electrode, which defines the baseline
potential for sensing and pacing. In one embodiment, a low
impedance common conductor such as DFT wire extends between the
indifferent electrode and the measurement module in order to
prevent the signaling pulses from affecting the sensing of the
electrogram. In another embodiment, the indifferent electrode is
connected to the sensing/pacing module by a third conductor. The
second conductor is electrically isolated from the body.
Advantageously, this conductor is physically contained by the outer
coaxial first conductor and the housings at each end. To ensure
electrical isolation at the CRM package, a spring contact without a
setscrew and seal are provided on the second inner conductor rather
than on the outer conductor as is customary in CRM devices. The
measurement module stores electrical energy from one or more power
pulses and applies an appropriate pacing pulse to a pacing
electrode when a pacing command is received from the CRM module
during the download interval. Importantly, the distance between the
pacing electrode and the indifferent is substantially reduced,
thereby greatly reducing any induced voltages during magnetic
resonance imaging (MRI) or electrocautery procedures. In one
embodiment, the sensor/pacing module stores electrical energy from
one or more power pulses and applies an appropriate pacing pulse to
the pacing electrode when a pacing command is received from the CRM
module, for example, during the download interval. In an
alternative embodiment, pacemaker timing is provided by circuitry
within the sensor/pacing module, autonomous from the CRM module. In
both embodiments, the sensor/pacing module may generate or store
electrical energy for application of an appropriate pacing pulse to
the pacing electrode at intervals defined by either the CRM module
or the circuitry within the sensor/pacing/measurement module
itself. In another embodiment, the pacing interval is modified or
synchronized with a second digital electrode in another location by
the generator module by downloading the appropriate command to the
sensor/pacing/measurement module.
[0274] In one embodiment, the circuitry includes current and
voltage limiting features known to those skilled in the art to
provide protection from defibrillator discharges, either from an
external or implantable defibrillator. In one embodiment,
series-connected oppositely oriented zener diodes are provided for
defibrillation protection as described, for example, by Langer
(U.S. Pat. No. 4,440,172, incorporated by reference herein).
[0275] Referring to FIG. 25, three embodiments are described to
implement a hybrid approach for performing pacing and physiological
sensing using the same lead.
[0276] In the first embodiment, the output voltage during the pacer
pulse is provided by a CRM device 306. Alternatively, in another
embodiment, an output voltage storage capacitor and a charge pump
are provided by a device 320, such as a POD.
[0277] Sensing may be performed according to at least three
different embodiments. In one embodiment, the circuitry is located
in a device 320, such as the POD, and a digital signal is provided
when a p-wave is detected. In the second embodiment, an electrode
328 is switched by switch 322 onto the lead conductor 324 either
before or after the output capacitor 326, and the CRM device 306
contains the sensing circuit. In this embodiment, the lead 324 may
be pre-charged to the electrode voltage to avoid generating signals
on the electrode 328. A third embodiment is a hybrid of the first
two. In the third embodiment, an IEGM signal is amplified by an
amplifier 330 and applied to the lead 324. For all three of these
options, IEGM sampling is time-multiplexed in the frame
sequence.
[0278] Either on-chip or back-to-back Zener diodes 332 are provided
in the device 320, thereby keeping the RF path (during MRI) small
in order to improve immunity.
[0279] 2. Upgrade from Stand-Alone to Combination System
[0280] Referring now to FIG. 26A, in one embodiment, the same
sensor and lead 318 can be used either as part of a Stand-Alone
system (such as a heart monitoring system, pressure monitoring and
feedback system, HEARTPOD.TM., POD, or apparatus for treating
congestive heart failure, as described above) or as part of a
combination system that includes a CRM or automated therapy system.
This flexibility allows for the implantation of a Stand-Alone
sensor that can be "upgraded" to include pacing and/or
defibrillation therapy if the need arises without having to implant
an additional lead. The combination system also allows the
communication coil 302 of the apparatus for treating congestive
heart failure (such as that described above with reference to FIG.
4) to be removed and replaced with a CRM 306. Furthermore, in one
embodiment, the sensor electronics (which in one embodiment are
located in a distal sensor package implanted within the patient's
heart, as schematically illustrated in FIG. 26B) include the
pace/sense circuitry that allows it to be used as a smart "digital"
electrode in conjunction with a CRM device, as described below, to
provide a digital pacemaker.
[0281] In an alternate embodiment, an additional lead conductor is
included to allow operation with pacing and sensing electronics
located within the CRM housing 306 of a CRM device. In one
embodiment, a sensor or sensor module 320 is coupled to the distal
end of a lead 318, which has a proximal IS1 connector 316, as is
familiar to those of skill in the art. In one embodiment, an
upgrade is performed by surgically opening the subcutaneous pocket,
unplugging the IS1 connector 316 from the RF coil antenna 302, or
pressure monitoring and feedback implanted module, and plugging the
lead 318 into an IS1 port 317 of a CRM housing 306, as described in
greater detail below.
[0282] In one embodiment, the sensor is externally powered either
by a tuned coil 303 (Stand-Alone mode) at 125 kHz (although any
other suitable frequency could be used) or "power" pulses (CRM
mode) at a frame frequency. In the Stand-Alone mode, data from the
sensor is telemetered to a patient advisory module (not shown)
using reflected impedance. Other telemetry schemes may also be
employed, such as disclosed, for example, in U.S. Pat. Nos.
4,681,111 and 5,058,581 to Silvian, incorporated herein by
reference. Electronics provided with the device, such as the POD or
distally implanted sensor module, contain circuitry that detects
whether an incoming signal is a 125 kHz signal (as is provided by
the pressure monitoring and feedback implanted module, in one
embodiment) or a frame power pulse (as is provided from a CRM
device, in one embodiment) at a frequency between 500 Hz and 20
kHz. This autosensing functionality allows the pressure monitoring
and feedback system described herein to be "upgraded," whereby the
additional functionality of a CRM system, such as a pacemaker or
defibrillator or other such device, is able to be provided by
merely changing, or swapping one implanted component, or module,
with another. At least two methods are provided for determining
which mode (Stand-Alone or combination) is operable, as described
below with reference to FIGS. 26A-D. One method is based on
frequency discrimination and the other is based amplitude
discrimination. In both cases, the signals are half-wave rectified
by rectifier 300 to provide power for the sensor (and pace/sense)
electronics. As is recognized by the skilled artisan, full-wave
rectification could be employed as an alternative. Two embodiments
of rectifier 300 are provided in FIGS. 26C-D.
[0283] In one embodiment, in the Stand-Alone mode (e.g., when a CRM
306 is not present), the 125 kHz signal is output from a tuned coil
302 that resides in a subcutaneous pocket. The 125 kHz signal is
rectified to provide DC power for the sensor electronics of the
sensor module 320 and a 125 kHz clock for operation and timing. A
shorting FET, which in one embodiment is located within
communications module 304, is placed across the 125 kHz input to
provide a reflected impedance signal that can be detected by the
external device for telemetry of the sensor(s) output. The FET is
disabled after power up until the POD has determined that the
Stand-Alone mode is operable. Although full wave rectification
could be used, in one embodiment, half wave rectification is
employed. Detection of the unused half cycle is one of the methods
used to differentiate between the two modes of operation. In one
embodiment, power is turned off to the pacing and sensing
electronics in the Stand-Alone mode.
[0284] In one embodiment, in the CRM mode, the sensor lead 318 is
attached to a CRM device 306 that provides a power pulse at a fixed
frame rate, a pace trigger signal, and apparatus for changing
memory registers in the POD. The power pulse is rectified to
provide DC power for the POD electronics. The reflected impedance
shorting FET used in the Stand-Alone mode is disabled at power up
and in CRM mode. A frame clock detector 308 is employed to obtain
the frame clock that is input to a DPLL 310 (digital phase lock
loop). The DPLL 310, by way of example, includes or is coupled to
an oscillator 311 with electronic frequency adjustment with its
output used for operation and timing for the POD electronics. This
clock is fed into a divide by N counter 314 whose output is coupled
to the other input to an up/down counter 312 whose output is
connected to the frequency adjustment of the oscillator 311 coupled
to the DPLL 310. The divide by N counter 314 output may be coupled
directly to the up/down counter 312 (or bit counter 312), or may be
coupled to a clock select module 314 which is coupled to the bit
counter 312, as shown in FIG. 26B. This provides for an internal
clock, which is N times the frame clock and is synchronized to the
frame clock. In another embodiment, an analog PLL is used instead
of a digital PLL. The DPLL 310 also provides a signal to indicate
the mode of operation (the frequency discrimination method). If the
DPLL 310 is locked at its limit (no sync), then Stand-Alone
operation is indicated. In the CRM mode, the CRM device 306 goes to
high impedance between power pulses during the upload period,
thereby allowing the POD to send sensor output(s) and a pacing
sense-detect signal to the CRM device 306.
[0285] Since the physical connection is different between the two
modes of operation, the detection mechanisms for mode determination
can be optionally latched at power up and then disabled to conserve
power.
[0286] One embodiment of the present invention provides for a novel
variation of a standard IS1 header 316. In conventional IS1
headers, typically a spring connector is employed for the outer
conductor and a setscrew is used for the inner conductor. Both the
125 kHz for the Stand-Alone device and the digital power/signaling
signals of the combination device need to be isolated from the body
and especially the heart in a fail-safe manner. Advantageously, in
one embodiment of the present invention, the active conductor is
the inner conductor of a coaxial lead and a spring connector is
used for the inner conductor in the IS1 header 316. This assures
that, even in a damaged lead or leaking setscrew seal, all leakage
paths to the body are completely surrounded by the common coax
outer conductor, and therefore isolated from the body.
[0287] In one embodiment, the system is designed to operate in at
least two different configurations, and in at least two modes of
operation. A first mode is the "Stand-Alone Configuration." A
second mode is "the CRM Combination" (or "Combination
Configuration"). One advantage of a multi-configuration system is
that it allows the device to be implanted as a Stand-Alone system
for CHF therapy and later to be upgraded for use with a CRM device
if the patient's condition changes. In the Combination
Configuration, in one embodiment, the sensor module 320 acts as a
pace/sense electrode for the CRM device.
[0288] In one embodiment, there are three modes of operation based
on the configuration: (1) A "Power-Up Mode" which is used to
automatically detect whether the Stand-Alone Configuration or the
Combination Configuration is present. This mode is entered into
when the power is applied to the sensor module 320. As described
below by way of example, at least two alternative methods are
described for detecting the configuration. Alternative methods will
be apparent to one skilled in the art; (2) A Stand-Alone
Configuration; and (3) A Combination configuration.
[0289] In one embodiment, the CRM module logic includes logic to
detect any problems with the sensor module 320. Should any
unrecoverable problem be detected, the CRM module (which in one
embodiment can optionally be limited to be under physician
supervision) stops the power pulses to the sensor module 320 and
restarts, thus allowing for a new power-up sequence.
[0290] Communication Block:
[0291] In one embodiment, a communication block 304 is provided. In
one embodiment, the communication block 304 is responsible for the
bidirectional communication. The Mode and PwrUp inputs define how
the device operates. Incoming communication in a preferred
embodiment is by FSK on the 125 kHz carrier for the Stand-Alone
Configuration and by digital command signals between power pulses
for the Combination Configuration. Outgoing communication in one
embodiment is by reflected impedance for the Stand-Alone
Configuration and by digital signals between power pulses for the
Combination Configuration. During the power-up mode, all outgoing
communication is suppressed. The figure for Combination
Configuration signals depicts a RZ code. One skilled in the art
will understand that other encoding methods, such as NRZ,
Manchester, etc., can also be used in accordance with several
embodiments of the current invention.
[0292] Voltage Detector Block:
[0293] In one embodiment, a voltage detector block 322 is provided.
In one embodiment, the voltage detector block 322 detects the
operating configuration after power is applied (during the power-up
mode). In one embodiment, it only needs to be powered during this
brief time and can be disabled to conserve power. The voltage
detector block 322 detects whether or not there are 125 kHz
excursions above Vdd, which may occur in the Stand-Alone
Configuration.
[0294] Clock Detector Block:
[0295] In one embodiment, a clock detector block 308 is provided.
In one embodiment, this block 308 is a comparator with two
thresholds that outputs a digital clock signal from the signal on
the lead. In the Stand-Alone Configuration, the threshold is set to
Vdd and the output is a 125 kHz square wave. In both the
Combination Configuration and Power-Up Mode, the threshold is set
to approximately 0.5V above Vss (although other thresholds may be
used) and the output is used to recover the frame sync which are
the power pulses in the combination mode and 125 kHz during the
power-up mode in the Stand-Alone Configuration. One reason for the
0.5 V threshold is to allow signaling pulses to have lower
amplitude than the power pulses and will not be erroneously
detected as clock pulses (and will also dissipate less power).
Alternatively, the midpoint supply voltage may be used as a
threshold, with equal amplitude power and signaling pulses,
provided that the DPLL 310 and related timing provides for a
defined gap between the last signaling pulse and the next power
pulse.
[0296] Clock Divider Block:
[0297] In one embodiment, a clock divider block 314 is provided. In
one embodiment, this block 314 divides down the 125 kHz to provide
a bit clock in the Stand-Alone configuration. It is disabled in the
CRM configuration.
[0298] Oscillator Block:
[0299] In one embodiment, an oscillator block 311 is provided. In
one embodiment, this block 311 contains a capacitor that is charged
up from Vss to a settable threshold voltage. A short reset pulse is
provided to fully discharge the capacitor after the threshold
reached and if a reset pulse is provided. The threshold is
determined by the oscillator control lines that specify to either
to increase or to decrease the threshold by a small delta V. In an
alternative embodiment, the capacitor is arranged in a binary array
and the DPLL 310 is an up/down counter.
[0300] Clock Select Block:
[0301] In one embodiment, a clock select block 314 is provided. In
one embodiment, this block 314 switches the bit clock to the sensor
module's internal oscillator output for the CRM Combination
Configuration and during the power-up mode. For the Stand-Alone
Configuration, the bit clock 314 is switched to the output of the
125 kHz clock divider.
[0302] Bit Counter Block:
[0303] In one embodiment, a bit counter block 312 is provided. In
one embodiment, this block 312 is a divide by N counter that is
reset by the Frame sync in the CRM configuration and during
power-up. It provides the bit timing sequence for each frame.
During power-up, in the Stand-Alone Configuration, it is
substantially held reset by the 125 kHz "frame sync" pulses.
[0304] DPLL Block:
[0305] In one embodiment, a DPLL block 310 is provided. In one
embodiment, the DPLL 310 provides the feedback to control the
internal oscillator frequency to be N times the frame sync. In one
embodiment, it also determines the configuration during power-up
mode by detecting that the Bit counter 312 is stuck reset.
[0306] Rectifier Block:
[0307] In one embodiment, a rectifier block 300 is provided. Two
alternative embodiments are shown in greater detail in FIGS. 26C-D.
In the embodiment of FIG. 26C, Vdd is tied to the outer lead
winding which is tied to the Indifferent Electrode. A schottky
diode is provided to protect the CMOS from the positive swing on
the inner "Lead" winding in the Stand-Alone configuration.
Alternatively, a full wave rectifier could be used. A separate
charge pump and pacing output voltage storage cap is provided to
generate and store the pace voltage. In the second rectifier
embodiment, which is illustrated in FIG. 26D, the charge pump and
storage cap are omitted from the sensor module. Instead, a MOS
switch is provided between Vdd and the Indifferent. This switch is
normally ON but is switched OFF during a pacer pulse so that the
pace voltage is stored in the CRM device and switched out to the
distal electrode. Additional circuitry is provided to handle
start-up and well switching issues.
[0308] Control Circuit Block:
[0309] Referring back to FIG. 26B, in one embodiment, a control
circuit block 324 is provided. In one embodiment, this block 324
provides substantially all the memory storage, logic and timing
required for operation.
[0310] Measurement Circuit Block:
[0311] In one embodiment, a measurement circuit block 326 is
provided. In one embodiment, this block 326 provides substantially
all the measurement circuitry to measure pressure, temperature,
etc.
[0312] Input Amp & Filter Block:
[0313] In one embodiment, an input amp & filter block 328 is
provided. In one embodiment, this block 328 contains an AC coupled
amplifier, filter and window comparator for the detection of heart
depolarization signals (P-wave and/or R-wave). The circuits for
this function are well known in the art. This block 328 is shown
connected to a separate sensing electrode. Normally the pacing and
sensing electrode are the same, which is still possible in this
invention by merely shorting these points together. Advantageously,
one embodiment provides for the possibility of separate pacing and
sensing electrodes without having to have a separate lead conductor
and extra connector pin. This allows each electrode to be optimized
independently for each electrode. In addition, the recovery
discharge voltage is eliminated on the sensing electrode, allowing
for sensing of the induced P or R-wave for capture verification
and/or threshold tracking. This advantage is due to the inclusion
of the pacing & sensing electronics remotely in the sensor
module. If two distinct electrodes are employed, additional
defibrillator protection may be needed for the sense amplifier.
This protection is relatively easy because the impedances can be
much higher and the induced currents are easily handled.
[0314] Defibrillation Protection Block:
[0315] In one embodiment, a defibrillation protection block 330 is
provided. In one embodiment, this block 330 is composed of two
back-to-back zener diodes or other method as is known in the
art.
[0316] One embodiment of an upgradeable system illustrated in FIG.
28 and FIG. 29. The system of FIG. 28 illustrates a "Stand-Alone"
embodiment, and includes an implantable housing 400 coupled to an
implantable lead 402 with a connector 404. In one embodiment, the
housing 400 is the housing 7 as described above. In another
embodiment, the lead 402 is the lead 318 or lead 10 as described
above. In one embodiment, connector 404 is the IS1 header 316, IS1
port 317, or connector 10, as described above. The connector 404
may be any connector known to those of skill in the art used to
couple an implantable lead to an implantable housing.
[0317] The lead 402 is connected to a sensor module (not shown) as
described in greater detail above. The lead 402 is also
electrically coupled to an indifferent electrode 406, as is well
known to those of skill in the art. The implantable housing 400 of
the Stand-Alone embodiment includes an antenna 408. In one
embodiment, the antenna 408 is the antenna 162 or coil 302 as
described in greater detail above. The antenna 408 may be any coil
of wire as is known to those of skill in the art, which may be used
for telemetry communications with an external device, such as a
patient advisory module (not shown), as described in greater detail
above with reference to FIGS. 4 and 5. In one embodiment, the
antenna 408 is coupled to the lead 402 via the connector 404, and
functions as described above.
[0318] One embodiment of a "combination" unit is described with
reference to FIG. 29. As described above, in one embodiment, when
the Stand-Alone unit is upgraded to provide CRM functionality in
addition to left atrial pressure sensing and patient feedback, the
housing of the Stand-Alone system may be exchanged with the housing
of a combination system without having to provide an additional
lead for cardiac rhythm management.
[0319] As illustrated in FIG. 29, in one embodiment, the housing
400 of the combination unit is coupled to a lead 402 via a
connector 404 as described above. In one embodiment, the lead is
coupled to an indifferent electrode 406, also as described above.
In one embodiment, the housing 400 of the combination unit is the
same as the housing 400 of a Stand-Alone unit, or CRM housing 306,
as described in greater detail above.
[0320] The housing 400 of the combination unit includes an antenna
408, battery 410, telemetry module 412, communication and power
pulses module 414, programming module 416, and pacing circuitry
418. The battery 410 provides power to the components within the
housing 410, as well as those within the sensor module (not shown),
as describe above. The telemetry module 412 provides communication
between the combination unit and the patient advisory module (not
shown). The communication and power pulses module 414 control
communication between the sensor module (not shown) and the housing
400 components as well as power distribution to the sensor module
from the battery 410. Programming module 416 provides programming
control over the system, including the pacing module 418, which
control the transmission of electrical pulses or stimuli as
required by the CRM device.
[0321] FIG. 29 illustrates one embodiment of a CRM Combination
configuration. In this configuration, the housing 400 contains a
battery 410 that powers both the CRM device and the sensor module
(not shown). The communication and power pulse circuit 414 provides
power to and communicates with the sensor module via the lead
conductor 402 using, in one embodiment, for example, the coding
scheme described with respect to FIG. 24. The communication circuit
414 also decodes physiological sensor signals, such as pressure
signals, a-wave and/or p-wave sense signals received from the
sensor module via the lead 402. Sense signals received by the
communication circuitry 414 are passed to the pacing circuitry 418
where they are used to determine if and when to provide a pacing
stimulus.
[0322] In one embodiment, the pacing circuitry 418 triggers a
pacing stimulus by sending a signal to the communication circuitry
414, which sets the appropriate pulse trigger bit to the sensor
module as described above with respect to FIG. 24. In one
embodiment, the pacing circuitry 418 delivers the pacing stimulus
to the lead 402 a predetermined interval after setting the pulse
trigger bit, and commanding the sensor module to allow the pacing
stimulus to pass from the lead 402 through the sensor module
electronics to the pacing electrode. In another embodiment, the
pacing stimulus is applied to the pacing electrode from a storage
capacitor within the sensor module when a pulse trigger bit is
received by the sensor module from the communication circuitry
414.
[0323] In one embodiment, various operational modes and parameters
are programmed using an external programming device (not shown)
that communicates with the implanted pacemaker transcutaneously
using telemetry system 412, which decodes programming commands from
a programmer and passes them to the programming circuitry 416. In
one embodiment, physiological sensor signals, such as but not
limited to pressure, temperature, or internal electrocardiogram
signals, are passed from the communication circuitry 414 to the
telemetry circuitry 412 for telemetry to the external patient
advisory module, such as the patient advisory module illustrated
and described above with reference to FIG. 4. In one embodiment,
physiological sensor signals are also communicated from the
communication circuitry 414 to the programming circuitry 416, where
they are used to at least partially to control the operation of the
pacemaker in response to the patient's condition.
[0324] 3. Automated Therapy
[0325] According to one embodiment of the current invention, a
method for treating cardiovascular disease in a medical patient
includes implanting a physiological sensor package and a therapy
delivery unit (e.g., the "treatment system") within the patient's
body, operating the physiological sensor package to generate a
signal indicative of a physiological parameter, communicating the
signals indicative of the physiological parameters to a signal
processing apparatus, operating the signal processing apparatus to
generate a signal indicative of an appropriate therapeutic
treatment, and communicating to the patient the signal indicative
of the appropriate therapeutic treatment. The patient may then
administer to him or herself the prescribed therapeutic treatment
indicated by the signal or instructions. In another embodiment, the
signal indicative of the appropriate therapeutic treatment is
communicated to an automated therapy unit to generate an automatic
therapy regime.
[0326] a. Dynamic Prescription
[0327] In one embodiment, the automatic therapy regime is based
upon a programmed dynamic prescription. "Dynamic prescription," as
used herein, shall mean the information that is provided to the
patient for therapy, including instructions on how to alter therapy
based on changes in the patient's physiologic parameters. The
instructions may be provided by a physician, practitioner,
pharmacist, caregiver, automated server, database, etc. The
information communicated to the patient includes authorizing new
prescriptions for the patient and modifying the patient's medicinal
dosage and schedule. The "dynamic prescription" information also
includes communicating information which is not "prescribed" in its
traditional sense, such as instructions to the patient to take bed
rest, modify fluid intake, modify physical activity, modify
nutrient intake, modify alcohol intake, perform a "pill count,"
measure additional physiological parameters, make a doctor's
appointment, rush to the emergency room, call the paramedics, etc.
One skilled in the art will understand that numerous other
instructions may be beneficially provided to the patient predicated
at least in part upon measurement of one or more physiological
parameters in accordance with various embodiments of the present
invention.
[0328] b. Therapy Delivery Units
[0329] According to another embodiment, a therapy delivery unit is
provided, including but not limited to a system for releasing
bioactive substances from an implanted reservoir, a system for
controlling electrical pacing of the heart, and cardiac assist
devices including pumps, oxygenators, artificial hearts, cardiac
restraining devices, ultrafiltration devices, intravascular and
external counterpulsation devices, continuous positive airway
pressure devices, and a host of related devices for treating
cardiovascular conditions where knowledge of the left atrial
pressure would be beneficial for optimal therapy delivery. Cardiac
electrical pacing may be controlled in response to changes in
physiological parameters in accordance with the present invention
by, for example, AV delay optimization or any number of other
methods, as are well known to one skilled in the art of
cardiology.
[0330] According to one embodiment of the invention, the therapy
delivery unit is implanted according to the methods described
herein for the pressure transducer.
[0331] i. Drug Infusion
[0332] In one embodiment of the invention, a drug delivery unit is
provided. In this embodiment, intravenous or subcutaneous, bolus or
continuous infusion of drug from an implantable drug delivery unit
can be triggered or regulated by the signal processing apparatus
when certain predefined conditions are met. In one embodiment,
automatic drug delivery or other therapeutic measure is used as a
last resort "rescue mode" when the monitored physiological
parameters indicate the patient's condition requires urgent
therapeutic response. Typically, in "rescue mode", the patient's
condition is not amenable to a change in oral medication dose (see
"Dynamic Prescription"). Thus, in one embodiment, this invention
includes both the dynamic prescription with patient signaling, and
automated therapy via electrical stimulation, drug infusion, or
other therapy delivery unit. Drugs that may be so administered
include but are not limited to natriuretic peptides (e.g.,
Natricor), diuretics (e.g., furosimide), and inotropes (e.g.,
epinephrine, norepinephrine, dopamine, dobutamine, milrinone). In
one embodiment, rescue mode emergency drug infusion,
defibrillation, or other therapy is performed automatically based
at least in part on signals indicative of the patient's condition
derived from the one or more sensors of the invention. In another
embodiment, rescue mode therapy is initiated by the present
invention only after receiving doctor authorization to deliver the
therapy. In one embodiment, doctor authorization is given by
entering a password into the external patient
signaling/communication module. This permits potentially dangerous
emergency therapy to be delivered only after consultation with and
authorization by a qualified healthcare professional.
[0333] In one embodiment, dosimetry for multiple drugs or other
associated therapeutic devices is relayed based on parameter values
as input to a parameter-driven prescription. In one embodiment, the
system essentially replicates, in the home setting, the way
inpatients are managed based on their doctor's standing orders in
the Intensive Care Unit (ICU) of a hospital. In the ICU, nurses
periodically look at real-time physiologic values from diagnostic
catheters, and administer medications based on predetermined orders
by the patient's attending physician. One embodiment of the present
invention accomplishes the same thing. In one embodiment, wireless
communications technology is integrated with diagnostic and
treatment methods that are well established in cardiology. As such,
the system is designed to be convenient and time-efficient for both
the patient and his physician. The combination of monitoring key
physiologic parameters and the patient's own physician's
prescription drive a real-time feedback loop control system for
maintaining homeostasis. Thus, in one embodiment, the system
comprises an integrated patient management system tightly and
directly linking implantable sensor diagnostics with pharmacologic
and other therapies. As a result, this therapeutic approach enables
better, more cost effective care, improves out-of-hospital time,
and empowers patients to play a larger and more effective role in
their own healthcare.
[0334] In one embodiment, a portable system for continuously or
routinely monitoring one or more parameters indicative of the
condition of a patient is provided. Depending upon changes in the
indicated condition, the system determines, based on
parameter-driven instructions from the patient's physician, a
particular course of therapy. The course of therapy is designed to
manage or correct, as much as possible, the patient's chronic
condition. In one embodiment, the system communicates the course of
therapy directly to the patient or to someone who assists the
patient in the patient's daily care, such as, for example, but not
limited to, a spouse, an aid, a visiting nurse, etc.
C. Telemetry
[0335] In one embodiment of the invention, one or more signals are
communicated between the permanently implanted components of the
system and a component of the system external to the patient's
body. In one embodiment, signaling from the implanted to the
external components is achieved by reflected impedance using radio
frequency energy originating from the external device, and
signaling from the external components to the internal components
is achieved by frequency or amplitude shifting of radio frequency
energy originating from the external device. Thus, in this
embodiment, the current invention allows for telemetry of data from
within the heart without transmitting radio frequency energy from
the implanted device, advantageously resulting in significantly
reduced power consumption compared to implants that perform
telemetry by transmitting signals from within the body.
[0336] In another embodiment, signaling from the implanted to the
external components is achieved through the metal housing of the
implanted device using the method of Silvian (U.S. Pat. No.
6,301,504) incorporated by reference in its entirety herein.
[0337] In yet another embodiment, signaling from the implanted
housing containing components of a CRM device is achieved via an
antenna embedded within a dielectric around the periphery of the
housing, as taught, for example, by Amundson et al. in U.S. Pat.
No. 6,614,406, included herein by reference.
D. Power
[0338] In one embodiment of the invention, the implanted apparatus
is powered by a battery located within an implanted housing,
similar to that of a cardiac pacemaker, as is well known in the art
of cardiac pacing. In another embodiment, the implanted apparatus
is powered by an external power source through inductive,
acoustical or RF coupling. In one embodiment, power is provided to
the implanted device using 125 kHz emissions emitted from an
electrical coil placed outside the body. In one embodiment power
and data telemetry are provided by the same energy signal. In one
embodiment of the system a second electrical coil is implanted
inside the body at a location under the skin near the patient's
collarbone, similar to the placement of the generator housing of an
implantable pacemaker.
E. Physical Location of System Components
[0339] In one embodiment of the present invention, the apparatus
for diagnosing and treating cardiovascular disease is modular and
consists of a plurality of modules. Each module contains hardware,
and may contain one or more software programs. The component
modules can be physically located in different places and their
functions can differ dependent on the particular design of the
modules. FIG. 4 shows one embodiment of the current invention, in
which the first implantable module 5 of the apparatus is implanted
within the patient. A patient advisory module 6 is located external
to the patient's body and generally resides with the patient or his
direct caregivers. A third module (not shown in FIG. 4) may reside
with the physician. Each module performs multiple functions and
some of the functions may be performed on multiple modules. In one
embodiment, the modules consist of component sub-modules that
perform a particular function, such as described above.
[0340] 1. Leads
[0341] Although the pressure transducer in the embodiment produces
an electrical signal indicative of pressures in its vicinity and,
accordingly, an electrical lead is used to transmit the signals to
the electronic circuitry, other types of pressure transducers may
be used as well. For example, the pressure transducer and lead
might comprise a tube filled with an incompressible fluid leading
from the site in the body where the pressure is to be measured back
to a transducer in another location. Signals in the form of
pressures in the incompressible fluid indicate pressures at the
site of interest, and those pressures are sensed by the transducer
and utilized by the electronic circuitry in generating signals
indicative of appropriate therapeutic treatments. Signals in other
forms may be used as well and may be transmitted, for example, by
fiber optic means, or by any other suitable electrical,
electromechanical, mechanical, chemical, or other mode of signal
transmission.
[0342] Moreover, although the signal lead in one embodiment is of
an appropriate length so that the housing containing the electronic
circuitry can be implanted in the region of the patient's shoulder,
in alternative embodiments the lead may be of virtually any useful
length, including zero. In one embodiment, an integrated unit is
used in which the pressure transducer is disposed directly on the
housing and the entire device is implanted inside or very near to
the site at which pressure measurement is desired, for example the
left atrium of the patient's heart.
II. SYSTEM OPERATION
A. Signal Processing
[0343] FIG. 27 is a schematic diagram of operational circuitry that
in one embodiment is located inside the housing 7 and is suitable
for use in accordance with one embodiment of the present invention.
The apparatus depicted in FIG. 27 includes digital processors, but
the same concept could also be implemented with analog circuitry,
as is well known to those of skill in the art.
[0344] As described above, in one embodiment, the system of the
invention includes a pressure transducer 73 permanently implanted
to monitor fluid pressure within the left atrium of the patient's
heart. Moreover, the system may include one or more additional
sensors 75 configured to monitor pressure at a location outside the
left atrium, or a different physical parameter inside the left
atrium or elsewhere. For each sensor 73, 75, a sensor lead 77, 80
conveys signals from the sensor 73, 75 to a monitoring unit 82
disposed inside the housing of the unit. Alternatively, several
sensors may be located in a compact sensor package or sensor module
as, for example, illustrated in FIGS. 1, 2, 4, 22 and 23. In this
case, the several sensors may share a single sensor lead for
conveying signals from the sensors to the monitoring unit or a
telemetry antenna. It should also be noted that the sensor lead
connecting the pressure transducer to the monitoring apparatus
might also be combined with or run parallel to another lead such as
an electrical EKG sensor lead or a cardiac pacing lead, either of
which might be placed in or near the left atrium.
[0345] In one embodiment, when the signal from the left atrial
pressure transducer 73 enters the monitoring unit 82, the signal is
first passed through a low-pass filter 85 to smooth the signal and
reduce noise. The signal is then transmitted to an
analog-to-digital converter 88, which transforms the signals into a
stream of digital data values, which are in turn stored in digital
memory 90. From the memory 90, the data values are transmitted to a
data bus 92, along which they are transmitted to other components
of the circuitry to be processed and archived. The stream of binary
digital values may be immediately transmitted to a telemetry device
external to the patient one bit at a time as they are generated
from the most significant bit to the least significant bit by a
successive approximation analog-to-digital converter. An additional
filter 95, analog-to-digital converter 97, and digital memory area
100 may be provided as shown for each optional sensor 75 whenever
such a sensor 75 is present. In another embodiment, several sensors
share one analog-to-digital converter.
[0346] In one embodiment, the digital data on the data bus 92, are
stored in a non-volatile data archive memory area 103. The archive
103 stores the data for later retrieval, for example, by a
physician at the patient's next regularly scheduled office visit.
The data may be retrieved, for example, by transcutaneous telemetry
through a transceiver 105 incorporated into the unit. The same
transceiver may serve as a route for transmission of signals into
the unit, for example, for reprogramming the unit without
explaining it from the patient. The physician may thereby develop,
adjust, or refine operation of the unit, for example, as new
therapies are developed or depending on the history and condition
of any individual patient. By way of an additional example,
reprogramming the implanted device could include changing the
sampling frequency for digitizing the pressure, IEGM or other
waveforms, or selecting which sensor data is to be monitored.
Devices for transcutaneous signal transmission are known in the art
in connection with pacemakers and implantable cardiac
defibrillators (collectively known as cardiac rhythm management
apparatus), and the transceiver used in the present invention may
be generally similar to such known apparatus.
[0347] In one embodiment of the present invention, the digital data
indicative of the pressure detected in the left atrium, as well as
data corresponding to the other conditions detected by other
sensors, where such are included, are transferred via the data bus
92 into a central processing unit 107, which processes the data
based in part on algorithms and other data stored in non-volatile
program memory 110. The central processing unit 107 then, based on
the data and the results of the processing, sends an appropriate
command to a patient signaling device 113, which sends a signal
understandable by the patient and based upon which the patient may
take appropriate action such as maintaining or changing the
patient's drug regimen or contacting his or her physician.
[0348] Circuits for extracting relevant components from a pressure
waveform are familiar to those skilled in the art. For example, a
low pass filter element may be used to extract the long-term
average, or "DC" component. In one embodiment, the outputs of
overlapping low pass filters, one designed to include only
frequencies lower than respiratory cycle frequencies, and the other
designed to include respiratory but not cardiac cycle frequencies,
are sampled at a fixed time in each cardiac cycle and subtracted to
derive the respiratory component. In general, the respiratory
contribution to the waveform is negative during inspiration and
positive during expiration, with a mean contribution of zero. Thus,
the long-term average of the pressure waveform is equal to the
average of the cardiac component. The term of the long-term average
is chosen to be long compared to the respiration rate but short
compared to the rate of mean pressure change due to changes in a
change in the patient's condition, so that slowly changing
physiological information relevant to managing the patient's
condition is not lost.
B. Signal Communication
[0349] In several embodiments of the invention, the patient
signaling device 113 comprises a mechanical vibrator housed inside
the housing of the system. In one embodiment, the vibrator delivers
a small, harmless, but readily noticeable electrical shock to the
patient. In some embodiments, a low power transmitter configured to
transmit information transcutaneously to a remote receiver, which
could include a display screen or other means for communicating
instructions to the patient. In one embodiment, the system includes
communication devices for communicating information back to a base
location. These communication devices include, but are not limited
to cellular or land-line telephone equipment or a device connected
to the Internet, for communicating information back to a base
location. In one embodiment, this is used, to transmit information
concerning the patient's condition back to a hospital or doctor's
office, or to transmit information concerning the patient's
prescription usage back to a pharmacy.
[0350] In one embodiment, the signal processing and patient
signaling components of the invention are combined into a patient
advisory module, external to the patient's body. The patient
advisory module further comprises a telemetry module to receive
pressure and other physiological data from the implanted sensor
system via wireless telemetry. This configuration has the advantage
that the external device may be based in part on a general purpose
computer such as a personal data assistant (PDA), allowing
increased flexibility and complexity in signal processing and
prescription algorithms. An additional advantage is that it
provides essentially unlimited storage for digital physiological
data from the patient, as well as for information on medications
and other relevant information to help the patient and physician
manage congestive heart failure.
[0351] Yet a further advantage of the externalized patient
signaling device component is that a much richer and easier to use
interface with the patient is facilitated using a display screen
and/or audio communication with the patient. In one embodiment, a
reminder function is incorporated in the external device such that
the patient is prompted to initiate measurement just prior to
scheduled medications or other therapy. The patient is then advised
of the appropriate doses of medications and/or other therapies
based on the measurements and his physician's dynamic
prescription.
[0352] In one embodiment, the patient advisory module is external
and serves as a treatment and medications record. In this use, the
patient will be asked to verify which of the prescribed medications
were taken and which were, for whatever reason, were skipped, thus
creating a record of compliance with the dynamic management
program. This function will permit the physician to better manage
the patient and, additionally, will improve patient compliance. Yet
another advantage of the externalized patient advisory module is
that it can be easily integrated with a cellular telephone or
PDA/cell phone combination, allowing automated telemetry of alerts
and/or physiological data to a remote health care provider such as
the patient's physician, hospital, nursing clinic, or monitoring
service.
[0353] Apparatus as described herein may also be useful in helping
patients comply with their medication schedule. In that case, the
patient advisory module could be programmed to signal the patient
each time the patient is to take medication, e.g., four times
daily. This might be done via an audio or vibratory signal as
described above. In versions of the apparatus where the patient
signaling device includes apparatus for transmitting messages to a
hand held device, tabletop display, or another remote device,
written or visual instructions could be provided. In one
embodiment, apparatus generates spoken instructions, for example,
synthesized speech or the actual recorded voice of the physician,
to instruct the patient regarding exactly what medication is to be
taken and when.
[0354] Where the system includes apparatus for communicating
information back to a base location, e.g., the hospital, doctor's
office, or a pharmacy, the system in one embodiment, tracks the
doses remaining in each prescription and to reorder automatically
as the remaining supply of any particular drug becomes low.
[0355] In one embodiment of this invention, the external device
communicates with a personal computer (PC) in the doctor's office
either directly when the patient is present for an office visit, or
via electronic communications, including, but not limited to, a
telephone modem or the internet. During this communication, data is
uploaded from the external device to the PC, including the records
of physiological measurements, symptoms, and medication compliance,
as well as information regarding the operation and calibration of
the implanted device. Software on the PC displays the patient
information, and the doctor enters a new dynamic prescription or
edits the existing one. The PC then downloads the new or edited
dynamic prescription to the external device. Re-calibration of the
pressure transducer in the external device may be performed
relative to a reference manometer in the physician's office.
[0356] In one embodiment, the physician's PC maintains a database
of all the patients under medical management by the physician using
the device of this invention. The database includes the patients
identifying, demographic, and medical information, the implantable
device's unique identification number. For each patient, the
database maintains a record of all data uploaded from the external
device, device calibration records, patient dynamic prescription
records, and compliance records.
[0357] In one embodiment, data stored in the external patient
advisory module is uploaded to the physician's PC at the time of
the patient's regular office visit. The external device is placed
in a data interface cradle connected to the PC, and the data is
transferred. In one embodiment of the data transfer, the external
device is a modified personal data assistant such as a Palm Pilot,
and the data interface cradle is the cradle used by such PDA
devices for data synchronization with a personal computer.
[0358] In another embodiment, the data from the external device is
uploaded to the physician PC via the Internet, telephone, or
cellular telephone network. In this case, the data may be uploaded
at regular intervals, or whenever the patient or physician
determines there is a need for physician review of the patient's
management.
[0359] The prescription editor is a software program on the
physician's PC that allows the physician to create, view, and
modify the dynamic prescription for each patient. The dynamic
prescription may consist of sets of prescribed treatments depending
on the values of one or more physiological measurements, and/or
patient symptoms, and/or changes and/or rates of change of
measurements or symptoms (collectively, input parameters). A
prescription editor allows the physician to define thresholds for
each input parameter and to define the combination of treatments to
be administered for each possible combination of input parameters.
In one embodiment, the prescription editor has a graphical user
interface that displays the possible combinations of input
parameter ranges and the corresponding treatments in a way that the
physician can clearly see that all possibilities have been defined
according to his intended management of the patient. In another
embodiment, the prescription editor provides for the entry and/or
editing by the physician of a set of rules relating data collected
from the patient and treatments to be administered or instructions
to be followed by the patient.
[0360] In one embodiment, the revised dynamic prescription and/or
calibration data is downloaded from the physician's PC to the
external device in the same way that data is uploaded from the
external device to the physician's PC. In one embodiment, a unique
identification number from the external device is used to verify
the correct match between the prescription and the patient. This
unique identification number is obtained by the external device
from the implanted device, which has a unique identification number
programmed into its integrated processor chip at the time of
manufacture. In one embodiment, a 27-bit unique identification code
is permanently programmed into the implanted device at the time of
manufacture. This identification number is sent along with data
communicated from the implanted device to the external device to
uniquely identify the implanted device to the external device
software.
C. Power Management
[0361] In one embodiment, the circuitry of the invention may also
include a power management module 115 configured to power down
certain components of the system between times when those
components are in use. Such components include, but are not limited
to, analog-to-digital converters 88, 97, digital memories 90, 100,
and central processing unit 107, as shown in FIG. 27. This helps to
conserve battery power and thereby extend the useful life of the
device so that it can remain operational inside the patient's body
for extended periods between maintenance or replacement. Other
circuitry and signaling modes may be devised by one skilled in the
art.
[0362] In one embodiment, the implanted pressure monitor operates
on transmitted power from outside the body, eliminating the need
for an implanted battery. This approach is particularly well suited
when periodic, as opposed to continuous, monitoring is required. In
one embodiment, 125-kHz radio-frequency energy is transmitted from
an external coil, through the patient's skin, and received by an
implanted antenna coil connected to the electronics package of the
implantable pressure monitor, as described above. The signal in the
antenna coil is rectified and used to charge a capacitor, which in
turn powers the measurement electronics. Low power telemetry of the
measured data is performed by varying the impedance of the antenna
coil circuit. In still another embodiment, the coil antenna is
incorporated into or immediately adjacent to the pressure sensor
within the heart.
III. EXAMPLES OF SYSTEM APPLICATION
A. Example 1
[0363] Exemplary modes of operation for an embodiment of the system
of the invention are described as follows. The following Example
illustrates various embodiments of the present invention and is not
intended in any way to limit the invention.
[0364] In one embodiment, the system is programmed to power up once
per hour to measure the left atrial pressure and other conditions
as dictated by the configuration of the particular system and any
other sensors that might be present. Left atrial pressure
measurements are taken at a 20-Hertz sampling rate for sixty
seconds, yielding 1200 data values reflective of the fluid pressure
within the left atrium. The central processing unit then computes
the mean left atrial pressure based on the stored values. Then, if
the mean pressure is above a threshold value predetermined by the
patient's physician, the central processing unit causes an
appropriate communication to be sent to the patient via the patient
signaling device.
[0365] A set of coded communications to the patient can be devised
by the treating physician and encoded into the device either at the
time of implantation or after implantation by transcutaneous
programming using data transmission into the non-volatile program
memory 110 via the transceiver 105. For example, assume that the
physician has determined that a particular patient's mean left
atrial pressure can be controlled at between 15 and 20 mm Hg under
optimal drug therapy. This optimal drug therapy might have been
found to comprise a drug regimen including 5 milligrams (mg) of
Lisinopril, 40 mg of Lasix, 20 milliequivalents (mEq) of potassium
chloride, 0.25 mg of Digoxin, and 25 mg of Carvedilol, all taken
once per day.
[0366] The patient is implanted with the device and the device is
programmed as follows. The device includes a pressure transducer
implanted across the atrial septum such that the transducer
responds to the difference in pressure between the right and left
atria. This differential pressure is independent of changes in
atmospheric pressure, and in most circumstances is well correlated
with, and thus indicative of, the left atrial pressure. The
device's programming provides for four possible "alert levels" that
are specified according to mean differential atrial pressure
detected by the transducer and computed in the central processing
unit, and that the patient signaling device is a mechanical
vibrator capable of producing pulsed vibrations readily discernable
by the patient.
[0367] At predetermined intervals, for example, hourly, daily,
weekly, monthly, 3-4 times per day, or in response to a detected
event, in response to a symptom, or in response to an instruction,
the device measures the patient's mean left arterial pressure as
described above, and determines the appropriate alert level for
communication to the patient according to programming specified by
the physician. For example, a mean left atrial pressure of less
than 15 mm Hg could be indicative of some degree of over-medication
and would correspond to alert level one. A pressure between 15 and
20 mm Hg would indicate optimal therapy and correspond to alert
level two. A pressure between 20 and 30 mm Hg would indicate mild
under-treatment or mild worsening in the patient's condition, and
would correspond to alert level three. Finally, a mean left atrial
pressure above 30 mm Hg would indicate a severe worsening in the
patient's condition, and would correspond to alert level four.
[0368] When the proper alert level is determined, the device sends
a two-second vibrating pulse to notify the patient that the device
is about to communicate an alert level through a sequence of
further vibrations. A few seconds later, a sequence of one to four
relatively short (one second) vibratory pulses, the number
corresponding to the applicable alert level, are made by the device
and felt by the patient. The patient can easily count the pulses to
determine the alert level, then continue or modify his own therapy
with reference to a chart or other instructions prepared for him by
the physician.
[0369] For example, two pulses corresponds to alert level two, an
optimal or near optimal condition for that particular patient. In
that case, the doctor's instructions tell the patient to continue
his or her therapy exactly as before. The signal for alert level
two is given once every 24 hours, at a fixed time each day. This
serves mainly to reassure the patient that the device is working
and all is well with his therapy, and to encourage the patient to
keep taking the medication on a regular schedule.
[0370] One pulse, in contrast, corresponds to alert level one, and
most likely some degree of recent over-medication. The doctor's
orders then notify the patient to reduce or omit certain parts of
his therapy until the return of alert level two. For example, the
doctor's instructions might tell the patient temporarily to stop
taking Lasix, and to halve the dosage of Lisinopril to 2.5 mg per
day. The coded signal is given to the patient once every twelve
hours until the return of the alert level two condition.
[0371] Three pulses indicates alert level three, a condition of
mild worsening in the patient's condition. Accordingly, the
doctor's instructions notify the patient to increase the diuretic
components of his therapy until alert level two returned. For
example, the patient might be instructed to add to his to his
normal doses an additional 80 mg of Lasix, twice daily, and 30 mEq
of potassium chloride, also twice daily. The level three alert
signal would be given every four hours until the patient's
condition returned to alert level two.
[0372] Four pulses indicates alert level four, indicating a serious
deterioration in the patient's condition. In this case, the patient
is instructed to contact his physician and to increase his doses of
diuretics, add a vasodilator, and discontinue the beta-blocker. For
example, the patient might be instructed to add to his therapy an
additional 80 mg of Lasix, twice daily, an additional 30 mEq of
potassium chloride, twice daily, 60 mg of Imdur, twice daily, and
to stop taking the beta-blocker, Carvedilol. The signal
corresponding to alert level four would be given every two hours,
or until the physician was able to intervene directly.
B. Example 2
[0373] In one embodiment, the system is configured as an externally
powered implantable device with a sensor implanted in the
intra-atrial septum. The pressure transducer of the sensor is
exposed to the pressure in the left atrium. In one embodiment, the
sensor is anchored in the septum such that the pressure transducer
is substantially flush with the left atrial wall in fluid contact
with blood in the left atrium. In another embodiment, the anchor is
designed such that the pressure sensor extends a predetermined
distance into the left atrium. In both these embodiments, the
pressure sensor package is located in the septum with its proximal
end extending back into the right atrium. A flexible lead extends
from the proximal end of the sensor package back through the right
atrium, into the superior vena cava, up to a subclavian vein, and
out through the wall of the subclavian vein, terminating at an
antenna coil assembly located in a subcutaneous pocket near the
patient's clavicle, similar to a pacemaker generator housing.
[0374] The temperature at the site of the sensor and an internal
electrocardiogram (IEGM) are also detected by the sensor. A digital
signal is communicated to an external telemetry device via an
antenna coil implanted under the patient's skin and connected to
the sensor by a flexible lead. The sensor is powered by radio
frequency energy received by the implanted coil from an external
coil connected to the external telemetry device. The external
telemetry device forms part of an external patient advisory module,
that also includes a battery power source, a signal processor, and
a patient signaling device that consists of a personal data
assistant (PDA) with a display screen and software for
communicating with the patient.
[0375] The external patient advisory module is programmed to alert
the patient at times determined by the physician, preferably at the
times the patient is scheduled to take prescribed medications,
typically one to three times per day. In one embodiment, the alert
consists of an audible alarm and the appearance of a written
message on the graphical interface of the patient-signaling device.
The message instructs the patient to perform a "heart check," that
is to obtain physiological measurements from the implanted device.
Instructions to the patient may include instructions to establish
certain standard conditions, such as sitting quietly in a chair,
prior to beginning the measurements. The patient is instructed to
place the external telemetry/power coil over the implanted antenna
coil, then to press a button to initiate the measurement sequence.
Once the patient presses the button, the external device begins
emits energy via the external coil to power and communicate with
the implanted device. In one embodiment the external device emits
an audible signal while communication is being established, then
emits a second audible signal distinct from the first when
communication has been established and while the measurement is
taking place. Once the measurement is concluded, typically after 5
to 20 seconds, a third audible signal, distinct from the first two,
is emitted to signal the patient that the measurement is
complete.
[0376] In one embodiment, the external device will further instruct
the patient, using its graphical interface, to enter additional
information relevant to the patient's condition, such as weight,
peripheral blood pressure, and symptoms. The signal processing
apparatus of the external device then compares the measured
physiological parameters from the implanted device, together with
information entered by the patient, with ranges and limits
corresponding to different therapeutic actions as predetermined by
the physician and stored in the external device as a "DynamicRx."
The prescribed therapeutic action will then be communicated to the
patient on the graphic display.
[0377] In one embodiment, the patient signaling apparatus will
prompt the patient to confirm that each prescribed therapy has been
performed. For example, if the therapy is taking a specific dose of
oral medication, the patient will be prompted to press a button on
the graphical interface when the medication has been taken. In one
embodiment of the invention, this information is used to keep track
of the number of pills remaining since the last time the patient's
prescription was filled, so that the patient or caregiver can be
reminded when it is time to refill the prescription.
[0378] As an example of a DynamicRx for a congestive heart failure
patient, the level and rate of change of left atrial blood pressure
(LAP) may be used by the physician to determine the dosage of
diuretic. If the LAP remains in the normal range for that patient,
the patient signaling device would display the normal dosage of
diuretic. As in Example 1 above, if the LAP falls below the
patient's normal range, the doctor may prescribe a reduction or
withholding of diuretic, and that instruction would appear on the
graphical interface. In another embodiment of DynamicRx the patient
may be instructed to take some other kind of action, such as
calling the physician or caregiver, altering diet or fluid intake,
or getting additional rest. Thus, the apparatus and methods of the
present invention allow the physician to conditionally prescribe
therapy for the patient, and to communicate the appropriate therapy
to the patient in response to dynamic changes in the patient's
medical condition.
[0379] In one embodiment, the physician enters the therapeutic plan
for the patient, e.g., the DynamicRx, on a personal computer and
the DynamicRx is then loaded from the PC into the patient advisory
module. In one embodiment, the patient advisory module is a PDA
using the PalmOS operating system, and the DynamicRx is loaded from
the physician's PC via the HotSync facility of PalmOS. Loading of
the DynamicRx from the physician's PC could be performed in the
physician's office, or could be performed over a telephone modem or
via a computer network, such as the Internet.
[0380] In one embodiment, DynamicRx software running on the PC
contains treatment templates that assist the physician in creating
a complete DynamicRx, such that appropriate therapies/actions are
provided for all possible values of the patient's physiological
parameters.
[0381] In one embodiment of the present invention, the DynamicRX
includes a patient instruction. In one embodiment, the patient
instruction may includes directions or instructions to take
medications, instructions to call 911, instructions to rest; or
instructions to call a physician or medical care provider. In
another embodiment of the present invention, one or more devices
are provided to enable a physician or medical care provider to
provide instruction to the patient. These devices include, but are
not limited to, workstations, templates, PC-to-Palm hotsync
operations, uploading processes, downloading processes, linking
devices, wireless connections, networking, data cards, memory
cards, and interface devices that permit the physician instruction
to be loaded onto a patient's signal processor. In another
embodiment, a user instruction is provided, where the user includes
a patient, a physician, or a third party.
C. Example 3
[0382] Heart failure patients implanted with the embodiments
described in the above two examples may at the time of such
implantation, or subsequently develop a medical indication for
concurrent implantation of a CRM device. For example, required
heart failure treatment with beta-blocking medication may slow the
heart rate sufficiently to induce symptoms such as fatigue, or may
prevent the heart rate from increasing appropriately with exertion,
a condition known as chronotropic incompetence. These conditions
are recognized indications for atrial pacing or atrial pacing with
a rate responsive type of pacemaker. Normally this involves the
placement of a pacemaker generator and an atrial pacing lead
usually positioned in the right atrial appendage. In many cases, a
dual chamber pacemaker is placed to synchronously pace the right
atrium via one lead and the right ventricle via a second pacing
lead. In other cases, such heart failure patients may have an
abnormality of electrical conduction within the heart such as is
known to occur with a condition called left-bundle branch block
that causes dysynchronous left ventricular contraction thereby
worsening heart failure. Implantation of a biventricular pacemaker
has been shown to improve many of these patients. Because severe
heart failure also carries an increased risk of sudden cardiac
death due to a ventricular cardiac tachyarrhythmia, many of these
patients are now being treated with implantable cardiac
defibrillators (ICD's). In some cases combination rhythm management
devices comprised of a biventricular pacemaker and an ICD are
implanted.
[0383] In such cases where a CRM device is needed, it would be
beneficial to the patient if the rhythm management device were
integrated with the heart failure management devices described by
Eigler, et al., in U.S. Pat. No. 6,328,699 and U.S. Patent
Application Publication Nos. 2003/0055344 and 2003/0055345, all of
which are incorporated by reference in their entireties, to utilize
the sensing lead yielding a pressure indicative of left atrial
pressure additionally as an atrial pacing lead. It would be further
beneficial if the LAP sensing lead system described in Example 2
could be upgraded to integrated with the heart failure management
device without removing or changing the LAP sensing lead.
[0384] In one embodiment, the implanted heart failure device of
Example 2 above is modified by replacing the implanted
communications coil with an appropriately integrated CRM generator
and additional pacing/ICD leads. The LAP sensing lead is connected
as the atrial pacing lead to the generator. The generator has
appropriate circuitry to power the sensing circuitry of the atrial
lead. LAP is read out by telemetry between the external PDA and the
telemetry coil in the housing of the integrated rhythm management
generator. If clinically appropriate, right and left ventricular
pacing or defibrillation leads can be placed and connected to the
generator. There are many potential benefits from such a combined
rhythm and heart failure management system in addition to the
clinical benefits from each individual system. Fewer leads need to
be placed in the heart and a single venous insertion site can be
used with the combined system. Atrial pacing from the intra-atrial
septum has been show to inhibit paroxysmal atrial fibrillation, an
arrhythmia common in heart failure patients. Patients can be
titrated to higher or more appropriate beta-blocker dose levels
with potentially increased survival benefits. Additionally, the LAP
sensor can be used to control pacing parameters. As described
above, the LAP waveform may be helpful in adjusting mechanical
left-sided AV delay to optimize LV filling. Also, when LAP is
within the desired normal range and thus the patient is not in
acute heart failure, synchronous ventricular pacing can be
inhibited to prolong battery life. It is understood by those
skilled in the art, such as cardiologists and cardiac surgeons,
that there may be additional clinical benefits bestowed by the
combination of heart failure and rhythm management devices.
[0385] While this invention has been particularly shown and
described with references to embodiments thereof, it will be
understood by those skilled in the art that various changes in form
and details may be made therein without departing from the scope of
the invention. For all of the embodiments described above, the
steps of the methods need not be performed sequentially.
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