U.S. patent application number 11/636404 was filed with the patent office on 2007-07-12 for methods and systems for measuring cardiac parameters.
Invention is credited to Joseph M. Ruggio, Mark Zdeblick.
Application Number | 20070161914 11/636404 |
Document ID | / |
Family ID | 32825223 |
Filed Date | 2007-07-12 |
United States Patent
Application |
20070161914 |
Kind Code |
A1 |
Zdeblick; Mark ; et
al. |
July 12, 2007 |
Methods and systems for measuring cardiac parameters
Abstract
Methods and systems of the present invention provide for
measurement of various cardiac parameters. Methods generally
involve causing a change in volume and/or pressure in a heart
chamber, measuring the change, and calculating at least one cardiac
parameter based on the change. Systems typically include at least
one actuator, at least one sensor, and a catheter or other device
for positioning at least partially in a heart chamber. In some
embodiments, the system may also include a controller, such as a
computer or other processor, an external actuator, an external
sensor, and/or an ECG device. Methods and systems of the invention
may be used to more accurately diagnose cardiac conditions in order
to make more informed treatment decisions.
Inventors: |
Zdeblick; Mark; (Portola
Valley, CA) ; Ruggio; Joseph M.; (Laguna Hills,
CA) |
Correspondence
Address: |
BOZICEVIC, FIELD & FRANCIS LLP (PRTS);(PROTEUS BIOMEDICAL,INC)
1900 UNIVERSITY AVENUE, SUITE 200
EAST PALO ALTO
CA
94303
US
|
Family ID: |
32825223 |
Appl. No.: |
11/636404 |
Filed: |
December 8, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10764127 |
Jan 23, 2004 |
7204798 |
|
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11636404 |
Dec 8, 2006 |
|
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|
60442441 |
Jan 24, 2003 |
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Current U.S.
Class: |
600/486 |
Current CPC
Class: |
A61B 5/02158 20130101;
A61B 5/1107 20130101; A61B 5/0205 20130101; A61B 5/6882 20130101;
A61B 5/029 20130101; A61B 5/02028 20130101; A61B 5/1473
20130101 |
Class at
Publication: |
600/486 |
International
Class: |
A61B 5/02 20060101
A61B005/02 |
Claims
1-78. (canceled)
79. A system for measuring one or more parameters of a heart, the
system comprising: a catheter comprising at least one sensor and at
least one actuator for introducing a known volume of fluid into at
least one chamber of the heart at a selected time during a heart
cycle to effect a volume change in the heart chamber; a fluid
source coupled with the catheter for providing fluid to the
actuator; and a processor coupled with the catheter for processing
data sensed by the at least one sensor.
80. A system as in claim 79, wherein the at least one sensor
comprises at least one of a pressure sensor and a volume
sensor.
81. A system as in claim 80, wherein the at least one sensor
further comprises at least one of a flow sensor for measuring blood
flowing from the heart and a vascular pressure sensor for measuring
pressure in a vessel extending from the heart.
82. A system as in claim 81, wherein the at least one flow sensor
or pressure sensor is disposed in a location to measure flow or
pressure in at least one of an aorta, a pulmonary artery, and a
coronary artery.
83. A system as in claim 79, wherein the at least one sensor
comprises at least one hydrophone.
84. A system as in claim 79, wherein the at least one sensor
comprises at least one ultrasound transducer for measuring a
distance within a chamber of the heart.
85. A system as in claim 84, wherein the at least one ultrasound
transducer comprises: a first pair of ultrasound transducers
coupled with the catheter in parallel with a longitudinal axis of
the catheter for measuring a first distance between the transducers
and the wall of the chamber of the heart; a second pair of
ultrasound transducers coupled with the catheter in an orientation
90-degrees rotated from the first pair of transducers for measuring
second and third distances to a wall of the heart chamber; and a
third pair of ultrasound transducers coupled with the catheter in
an orientation 90-degrees rotated from the first and second pairs
of transducers for measuring fourth and fifth distances to a wall
of the heart chamber.
86. A system as in claim 79, wherein the at least one actuator
comprises at least one of a fluid outlet port and an expandable
balloon, the expandable balloon being expandable by introducing the
fluid into the balloon.
87. A system as in claim 79, further comprising an
electrocardiogram device coupled with the processor for measuring
the heart cycle.
88. The system as in claim 79, wherein said system is configured to
cause a change in at least one of volume and pressure in a heart
chamber at a selected time during a heart cycle; measure a change
in at least one characteristic of the heart chamber which occurs in
response to the change in at least one of volume and pressure; and
calculate at least one cardiac performance parameter based on a
ratio of the measured change in the characteristic to the caused
change.
89. The system as in claim 88, wherein said system is configured to
repeat the causing a change, measuring and calculating steps over a
series of two or more consecutive heart cycles.
90. The system as in claim 88, wherein said system is configured to
measure a change in at least one pressure within the heart
chamber.
91. The system as in claim 88, wherein said system is configured to
measure a change in at least one volume within the heart
chamber.
92. The system as in claim 88, wherein said system is configured to
measure a change in at least one pressure and a change in at least
one volume within the heart chamber.
93. The system as in claim 88, wherein said system is configured to
measure a change in at least one flow rate of blood flowing out of
the heart chamber which occurs in response to the volume and/or
pressure change; and calculate at least one flow-related parameter
of the heart chamber based on a ratio of the measured change in the
flow rate to the volume and/or pressure change.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims the priority benefit of U.S.
Provisional Patent Application No. 60/442441 (Attorney Docket No.
21308-000800US), filed Jan. 24, 2003, the full disclosure of which
is hereby incorporated by reference. The present application is
related to U.S. patent application Ser. Nos.: 10/______ (Attorney
Docket No. 21308-000710US); and 10/______ (Attorney Docket No.
21308-001110US); both of which are filed concurrently with the
present application, and both of which are hereby incorporated
fully by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to medical devices
and methods. More particularly, the present invention relates to
medical devices, systems, and methods for determining cardiac
performance parameters based on data obtained from an intravascular
or intracardiac catheter device.
[0004] Intravascular and intraluminal interventions and monitoring
have become essential in modem cardiology and other medical fields.
Of particular interest to the present invention, a variety of
intravascular and intracardiac catheters, implantable sensors, and
other devices and systems have been developed for monitoring
cardiac performance.
[0005] The ability to adequately treat patients suffering from or
at risk of cardiovascular diseases can be greatly enhanced by
frequent, or real time continuous, monitoring of cardiac
performance and function. For example, patients suffering from
congestive heart failure could titrate dosages of certain
medications if more information were available and information were
available more often, relating to cardiac performance and function
and how they have responded to drug treatment. Additionally, the
need for surgical intervention could also be better assessed if
better cardiac performance data were available. For example, it is
often difficult to distinguish compromised cardiac valvular
function due principally to aortic stenosis or mitral regurgitation
from other heart conditions such as myocardial insufficiency that
causes reduced pumping ability, especially when moth conditions
co-exist.
[0006] For these reasons, it would be desirable to provide improved
devices, systems, and methods for monitoring cardiac performance
and function both in and outside of medical facilities. Such
improved devices, systems, and methods should allow for measuring a
variety of mechanical, biological, and chemical parameters related
to cardiac performance and function and analyzing calculated
cardiac performance values based on such measured performance
characteristics. Preferably, the devices and apparatus will include
one or more intravascular catheters which allow for periodic or
continuous collection of in situ cardiac performance data. The
systems may then calculate physiodynamic cardiac performance
parameters based on the measured internal and external performance
data which has been collected. At least some of these objectives
will be met by the inventions described hereinafter.
[0007] 2. Description of the Background Art
[0008] Catheters and other intravascular and intracardiac devices
for measuring various cardiac, physiological parameters are
described in co-pending U.S. patent application Ser. No.
10/734,490, (Attorney Docket No. 21308-000510US), entitled "Method
and System for Monitoring and Treating Hemodynamic Parameters,"
filed on Dec. 11, 2003, and commonly assigned with the present
application, the full disclosure of which is hereby incorporated by
reference. Other catheters and implantable sensors capable of
measuring various physiologic parameters in the heart and/or
vasculature are described in U.S. Pat. Nos. 5,814,089; 6,328,699
B1; 6,438,408 B1; U.S. Patent Publication Nos. 2001/0053882 A1;
2001/0047138 A1; 2002/0077568 A1; 2002/0111560 A1; 2002/0151816 A1;
2002/0156417; 2002/0169445; and PCT Publication WO 02/065894 A2.
The full disclosures of each of these patents and patent
publications are incorporated herein by reference.
BRIEF SUMMARY OF THE INVENTION
[0009] Methods and systems of the present invention provide for
measurement of various cardiac parameters. Methods generally
involve causing a change in volume and/or pressure in a heart
chamber, measuring the change, and calculating at least one cardiac
parameter based on the change. Systems typically include a catheter
or other device for positioning at least partially in a heart
chamber and including at least one actuator and at least one
sensor. A monitoring device such as those described in U.S. patent
application Ser. No. 10/734,490, which was previously incorporated
by reference, may be used. In some embodiments, an implantable
device such as those described in U.S. patent application Ser. No.
60/442,441, which was previously incorporated by reference, may
also be used. In some embodiments, the system may also include a
controller, such as a computer or other processor, an external
actuator, an ECG device, an injector device and/or the like.
Methods and systems of the invention may be used to more accurately
diagnose cardiac conditions as well as precisely establish disease
severity and likely response to therapeutic interventions in order
to make patient specific treatment decisions.
[0010] In one aspect of the present invention, a method for
measuring a cardiac performance parameter includes: causing a
change in at least one of volume and pressure in a heart chamber at
a selected time during a heart cycle; measuring a change in at
least one characteristic of the heart chamber which occurs in
response to the volume change and/or the pressure change; and
calculating at least one parameter of the heart chamber based on a
ratio of the measured change in the characteristic to either the
volume change or the pressure change. Similar measurements of
various hemodynamic parameters may be made after changes induced by
alterations in heart rate, electrochemical coupling,
electrophysiological timing, and peripheral vascular changes.
[0011] In some embodiments, causing the change involves introducing
a volume of fluid into the heart chamber during diastole. The fluid
may be constrained or unconstrained. For example, introducing the
volume of fluid may involve releasing the fluid within the heart
chamber via one or more apertures in a catheter positioned in the
chamber. More specifically, introducing the volume of fluid may
involve inflating an expandable balloon coupled with a catheter
positioned in the heart chamber. For example, inflating the balloon
may involve inflating the balloon during systole of the heart and
deflating the balloon during diastole of the heart immediately
following the systole. Alternatively, introducing the volume of
fluid involves: inflating a balloon within the heart chamber during
systole; deflating the balloon during diastole imnediately
following the systole; and releasing an amount of unconstrained
fluid within the heart chamber during the diastole. For example,
the balloon may be deflated by a volume equal to the amount of the
released fluid. Alternatively, the balloon may be deflated by a
volume greater than the amount of the released fluid. In some
embodiments, causing the change comprises activating a hydrophone
at least once during diastole. The hydrophone may be activated at
any suitable frequency, but in some embodiments it is activated at
a frequency of about 200 Hz. Further embodiments involve changes in
diastolic filling period and post-extrasystolic potentiation
related measurements, as occurs with spontaneously or exogenously
induced paroxysmal ventricular tachycardia ("PVCs"). Still other
embodiments involve measuring changes induced by exercise,
alteration in heart rate and loading or unloading conditions, and
predicting response to electrophysiological or pharmacological
stimuli or interventions.
[0012] Optionally, a method may further include measuring the heart
cycle using an electrocardiogram device, with the selected time
during the heart cycle being selected using the electrocardiogram
measurement. In another embodiment, the method may comprise
measuring the heart cycle using at least one sensor on a catheter
positioned in the heart chamber, wherein the selected time during
the heart cycle is selected using the sensor measurement. The
timing of various steps may be different in different embodiments.
For example, in one embodiment, the measuring step is performed
immediately after causing a change in at least one of volume and
pressure. In another embodiment, the measuring step is performed
during at least a portion of the heart cycle after the change in at
least one of the volume and pressure. Optionally, the method may
further comprise causing a change, measuring and calculating steps
over a series of two or more consecutive heart cycles.
[0013] In one embodiment, measuring the change comprises measuring
a change in at least one pressure within the heart chamber. For
example, measuring the change in pressure may involve measuring a
change in end-diastolic pressure and a change in end-systolic
pressure. In such embodiments, calculating the at least one
parameter may involve calculating a cardiac pressure reserve,
comprising: calculating a first difference between a first
end-systolic pressure and a second end-systolic pressure;
calculating a second difference between a first end-diastolic
pressure and a second end-diastolic pressure; and dividing the
first difference by the second difference. The method may
optionally further include providing at least one of the
end-diastolic pressures, the end-systolic pressures and the cardiac
pressure reserve for display on a display device. For example, the
providing step may involve providing data in the form of a plot,
with at least one end-diastolic pressure on one axis of the plot
and at least one end-systolic pressure on a perpendicular axis of
the plot. Characteristics and parameters may be measured and
calculated in any heart chamber, but in one embodiment, measuring
the change comprises measuring a change in left ventricular
end-diastolic pressure and a change in left ventricular
end-systolic pressure.
[0014] In another embodiment, measuring the change involves
measuring a change in at least one volume within the heart chamber.
For example, measuring the change may include measuring a change in
end-diastolic volume and a change in end-systolic volume. In some
embodiments, calculating the parameter comprises calculating a
volume reserve, which involves: calculating a first difference
between a first end-systolic volume and a second end-systolic
volume; calculating a second difference between a first
end-diastolic volume and a second end-diastolic volume; and
dividing the first difference by the second difference. The method
may optionally further include providing at least one of the
end-diastolic volumes, the end-systolic volumes and the volume
reserve for display on a display device. For example, the providing
step may involve providing data in the form of a plot, with at
least one end-diastblic volume on one axis of the plot and at least
one end-systolic volume on a perpendicular axis of the plot.
Measuring the change, in some embodiments, involves measuring a
change in a left ventricular end-diastolic volume and a change in a
left ventricular end-systolic volume.
[0015] In some embodiments, measuring the change comprises
measuring a change in at least one pressure and a change in at
least one volume within the heart chamber. Measuring the change,
for example, may involve measuring a change in end-diastolic volume
and a change in end-diastolic pressure. The end-diastolic moment
may be determined using the volume sensor, as ventricular volume is
at a maximum at end-diastole. In this embodiment, the method may
further include providing pressure and volume data as a plot, with
at least one volume on one axis of the plot and at least one volume
on a perpendicular axis of the plot. Calculating the at least one
parameter may involve calculating a lusitropic stiffness of the
heart chamber, which involves: calculating a first difference
between a second end-diastolic pressure and a first end-diastolic
pressure; calculating a second difference between a second
end-diastolic volume and a first end-diastolic volume; and dividing
the first difference by the second difference. The method may
further involve providing at least one of the volumes, the
pressures and the lusitropic stiffness for display on a display
device. In another embodiment, calculating the at least one
parameter comprises calculating a lusitropic compliance of the
heart chamber, which involves: calculating a first difference
between a second end-diastolic volume and a first end-diastolic
volume; calculating a second difference between a second
end-diastolic pressure and a first end-diastolic pressure; and
dividing the first difference by the second difference. In various
embodiments, methods may further include providing at least one of
the volumes, the pressures and the lusitropic compliance for
display on a display device. In some embodiments, measurements may
be taken during isovolumetric relaxation and isovolumetric
contraction.
[0016] In yet another embodiment, measuring the change comprises
measuring a change in end-systolic volume and a change in
end-systolic pressure. The end-systolic moment may be determined
using the volume sensor, as ventricular volume is at a minimum at
end-systole. Some embodiments may further comprise providing volume
and pressure data as a plot, with at least one volume on one axis
of the plot and at least one pressure on a perpendicular axis of
the plot. Calculating the at least one parameter, in one
embodiment, comprises calculating an inotropic stiffness of the
heart chamber, which involves: calculating a first difference
between a second end-systolic pressure and a first end-systolic
pressure; calculating a second difference between a second
end-systolic volume and a first end-systolic volume; and dividing
the first difference by the second difference. This method may also
include providing at least one of the volumes, the pressures and
the inotropic stiffness for display on a display device.
[0017] In another embodiment, calculating the at least one
parameter comprises calculating an inotropic compliance of the
heart chamber, which includes: calculating a first difference
between a second end-systolic volume and a first end-systolic
volume; calculating a second difference between a second
end-systolic pressure and a first end-systolic pressure; and
dividing the first difference by the second difference. Again, any
of the volumes, the pressures and the inotropic compliance may be
provided for display on a display device.
[0018] In another embodiment, the measuring and calculating steps
include: continuously measuring a pressure and volume in the heart
chamber during at least two heart cycles, a first of the heart
cycles occurring before the change-causing step; calculating a
first integral of the product of the pressure and the volume as the
volume increases due to the change-causing step; calculating a
second integral of the product of the pressure and the volume as
the volume decreases; and calculating a myocardial work of the
heart chamber by subtracting the second integral from the first
integral. Optionally, this method may further include: calculating
a first myocardial work for the first heart cycle; calculating a
second myocardial work for a second heart cycle; measuring a first
end-diastolic pressure for the first heart cycle and a second
end-diastolic pressure for the second heart cycle; and calculating
a myocardial reserve by dividing a difference between the second
and first myocardial works by a difference between the second and
the first end-diastolic pressures. Such a method may further
include: calculating a body surface area; and calculating a
myocardial reserve index by dividing the myocardial reserve by the
body surface area. Myocardial work may be calculated for a left
ventricle of a heart, the right ventricle of a heart, or any other
chamber.
[0019] In yet another embodiment, a method as described above may
further include: measuring a change in at least one flow rate of
blood flowing out of the heart chamber which occurs in response to
the volume and/or pressure change; and calculating at least one
flow-related parameter of the heart chamber based on a ratio of the
measured change in the flow rate to the volume and/or pressure
change. In such embodiments, measuring the change in the flow rate
may involve measuring at least one flow rate in an aorta.
Alternatively, measuring the change in the flow rate may involve
measuring at least one flow rate in at least one pulmonary
artery.
[0020] In one embodiment, calculating the flow-related parameter
comprises calculating at least one stroke volume of a heart from
which the flow rate is measured, and the method further includes:
estimating a first cardiac output for the heart; measuring a pulse
rate of the heart; calculating a first stroke volume by dividing
the first cardiac output by the heart rate; calculating a first
integral of the flow rate over a number of heart cycles;
calculating a second stroke volume by dividing the first integral
by the number of heart cycles; calculating a scaling factor by
dividing the first stroke volume by the second stroke volume;
calculating a selected integral of the flow rate during a selected
heart cycle; and calculating the selected stroke volume by
multiplying the selected integral by the scaling factor. In some
embodiments, the first cardiac output is estimated using at least
one of Fick's method and a dilution method. In some embodiments,
the method further includes determining a selected cardiac output
by dividing the selected stroke volume by a time of duration of the
selected heart cycle. The purpose of this calibration procedure is
to allow the catheter system to measure the stroke volume and
effective cardiac output of each heart cycle. Current methods of
Fick or dilution average the cardiac output over many heart cycles.
Such embodiments may additionally involve, for example measuring a
body surface area, and calculating a cardiac index by dividing the
selected cardiac output by the body surface area.
[0021] Some embodiments further include: determining a first
selected cardiac output and a second selected cardiac output for
first and second heart cycles; measuring first end-diastolic
pressure and a second end-diastolic pressure for the first and
second heart cycles; and calculating a cardiac reserve by dividing
a difference between the second and first selected cardiac outputs
by a difference between the second and first end-diastolic
pressures. For example, the method may further involve: measuring a
body surface area, and calculating a cardiac reserve index by
dividing the calculated cardiac reserve by the body surface
area.
[0022] In one embodiment, the method further comprises: calculating
a first stroke volume and a second stroke volume for first and
second cardiac cycles; measuring first end-diastolic pressure and a
second end-diastolic pressure for the first and second heart
cycles; and calculating a stroke reserve by dividing a difference
between the second and first calculated stroke volumes by a
difference between the second and first end-diastolic pressures.
This method may further include: measuring a body surface area; and
calculating a stroke volume reserve index by dividing the
calculated stroke volume reserve by the body surface area.
Optionally, it may further comprise: measuring an average systolic
pressure in at least one outflow artery adjacent the heart;
measuring an average diastolic pressure in the heart chamber;
calculating a difference between the average systolic pressure and
the average diastolic pressure; and calculating a stroke work by
multiplying the difference by the stroke volume.
[0023] In some embodiments, the method further comprises:
calculating a first stroke work and a second stroke work for first
and second cardiac cycles; measuring first end-diastolic pressure
and a second end-diastolic pressure for the first and second heart
cycles; and calculating a stroke work reserve by dividing a
difference between the second and first calculated stroke works by
a difference between the second and first end-diastolic pressures.
Optionally, the method may further include: measuring a body
surface area; and calculating a stroke work reserve index by
dividing the calculated stroke work reserve by the body surface
area. The method may also optionally include measuring
post-systolic potentiation and its ability to estimate myocardial
reserve.
[0024] In the above embodiments, the at least one outflow artery
may be an aorta, at least one pulmonary artery, or any other
suitable outflow artery. The above embodiments may optionally
further involve calculating a cardiac efficiency by dividing the
stroke work by the myocardial work.
[0025] In one embodiment, a method includes: calculating a first
stroke volume and a second stroke volume for first and second
cardiac cycles; measuring first end-diastolic volume and a second
end-diastolic volume for the first and second heart cycles; and
calculating a cardiac amplification by dividing a difference
between the second and first calculated stroke volumes by a
difference between the second and first end-diastolic volumes.
[0026] In another aspect of the invention, a system for measuring
one or more parameters of a heart includes: a catheter comprising
at least one sensor and at least one expandable element, usually
comprising an actuator for introducing a known volume of
constrained or unconstrained fluid into at least one chamber of the
heart at a selected time during a heart cycle to effect a volume
change in the heart chamber; a fluid source coupled with the
catheter for providing fluid to the actuator; and a processor
coupled with the catheter for processing data sensed by the at
least two sensors. In some embodiments, the sensor may include at
least one of a pressure sensor and a volume sensor. Optionally, the
sensor may further comprises at least one of a flow sensor for
measuring blood flowing from the heart and a vascular pressure
sensor for measuring pressure in a vessel extending from the heart.
Alternatively, the catheter could comprise a means for deforming a
heart chamber, such as a pusher for outwardly deflecting or
otherwise mechanically reshaping the heart chamber to induce a
change in pressure or change in volume. In one embodiment, a flow
meter may be included to measure distensibilty characteristics of a
heart chamber.
[0027] In some embodiments, the flow sensor or pressure sensor is
disposed in a location to measure flow or pressure in at least one
of an aorta and a pulmonary artery. In some embodiments, at least
one sensor comprises a hydrophone. In some embodiments, the sensor
comprises at least one ultrasound transducer for measuring a
distance within a chamber of the heart. In some embodiments, for
example, the ultrasound transducer comprises: a first pair of
ultrasound transducers coupled with the catheter in parallel with a
longitudinal axis of the catheter for measuring a first distance
between the transducers and the wall of the heart chamber; a second
pair of ultrasound transducers coupled with the catheter in an
orientation 90-degrees rotated from the first pair of transducers
for measuring second and third distances to a wall of the heart
chamber; and a third pair of ultrasound transducers coupled with
the catheter in an orientation 90-degrees rotated from the first
and second pairs of transducers for measuring fourth and fifth
distances to a wall of the heart chamber.
[0028] Any actuator may be suitable for use in the system. For
example, an actuator may comprise at least one of a fluid outlet
port and an expandable balloon, the expandable balloon being
expandable by introducing the fluid into the balloon. In some
embodiments, the system further includes an electrocardiogram
device coupled with the processor for measuring the heart cycle
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] FIG. 1 illustrates a catheter-based cardiac performance
monitoring system in accordance with the principles of the present
invention.
[0030] FIG. 2 is a schematic illustration of the system according
to FIG. 1, including interfaces between various components of the
system.
[0031] FIG. 3 illustrates a patient's heart with a catheter in
place, having multiple sensors and an actuator, according to one
embodiment of the present invention.
[0032] FIG. 4A illustrates a pressure/volume curve which may be
derived according to principles of the present invention in some
embodiments.
[0033] FIG. 4B illustrates a stroke work/pressure curve which may
be derived according to principles of the present invention in some
embodiments.
[0034] FIG. 5A illustrates an induced change in pressure/volume
curves which may be derived in some embodiments, according to
principles of the present invention.
[0035] FIG. 5B illustrates the induced change according to FIG. 5A
in a stroke work/pressure curve.
[0036] FIG. 6 illustrates a change in pressure in a heart chamber
over time, the change induced by an actuator according to
principles of the present invention.
[0037] FIG. 7. illustrates data such as shown in FIG. 7 after
passing through a low-pass filter according to principles of the
present invention.
[0038] FIG. 8 illustrates data such as shown in FIGS. 6 and 7 after
passing through a high-pass filter according to principles of the
present invention.
[0039] FIG. 9 illustrates stiffness of a heart chamber over time,
as derived from data such as that illustrated in FIGS. 6-8
according to principles of the present invention.
[0040] FIG. 10 illustrates a sensor having multiple ultrasound
transducers, as may be used in an embodiment of the present
invention.
[0041] FIG. 11 illustrates a catheter in place in a patient's
heart, having an ultrasound sensor such as the one illustrated in
FIG. 10.
DETAILED DESCRIPTION OF THE INVENTION
[0042] The present invention is directed at methods, systems, and
apparatus for monitoring one or more patient parameters,
particularly cardiac performance parameters. The apparatus of the
present invention typically includes a catheter having one or more
sensors and one or more actuators. One such catheter, for example,
is described in U.S. patent application Ser. No. 10/734,490,
entitled "Method and System for Monitoring and Treating Hemodynamic
Parameters," previously incorporated by reference. Systems of the
present invention typically include a catheter, an external
actuation device, and a controller. In some embodiments, systems
may also include an electrocardiogram (ECG) device, other similar
heart monitoring device(s), thermistors, cardiac output measuring
consoles, injector devices, phonocardiography devices or the like
for use in conjunction with the catheter. Additionally, some
embodiments may employ one or more implantable devices, such as
those described in A monitoring device such as those described in
U.S. patent application Ser. No. 10/734,490, entitled "Method and
System for Remote Hemodynamic Monitoring," which was previously
incorporated by reference. Methods of the present invention
generally involved causing a change in a characteristic of a heart,
measuring the change, and calculating a cardiac parameter based on
the change.
[0043] Referring now to FIG. 1, an exemplary system 100 constructed
in accordance with the principles of the present invention
comprises a catheter device 102 placed in a heart H of a patient P,
a controller 108 coupled with catheter device 102, and an external
actuator 110 coupled with controller 108 and catheter device 102.
As will be described further below, catheter device 102 typically
includes one or more sensors 104 and one or more actuators 106 and
can be placed in any suitable location in the heart H or
vasculature. Sensors 104 may be adapted to measure a variety of
physiological parameters characteristic of heart function, while
actuators 106 may be adapted to effect a change within a chamber,
multiple chambers, or other areas in or around the heart H.
Controller 108 typically receives data from sensors 104 and also
activates various components of catheter 102, as well as external
actuator 110. Controller 108 may also receive data from other
various components, such as an ECG device. External actuator 110
generally activates one or more actuators 106 on catheter 102, via
instructions from controller 108.
[0044] Systems according to the present invention may take a
variety of specific forms, including both specialized and
off-the-shelf equipment. Components shown in FIG. 1 may be combined
and/or additional components may be added to system 100. Usually,
the catheter device 102 will be specially fabricated in accordance
with the principles of the present invention, although it may be
possible, in some instances, to employ more conventional sensor
devices which may be commercially acquired now or in the future.
Furthermore, the external controller 108 or external actuator 110
may at least partly comprise commercially available equipment.
Often, general purpose computers and workstations may be programmed
to perform many of the functions and calculations of the systems
and methods of the present inventions.
[0045] Referring now to FIG. 2, the various components of system
100 illustrated in FIG. 1, as well as an ECG device 210, are shown
with arrows designating directions in which data may flow between
components of system 100 in some embodiments. For example, data may
flow from controller 108 to catheter 102, such as data activating
one or more sensors, energy may be transmitted from controller 108
to catheter 102 and the like. Catheter 102 may, in turn, transmit
sensed data to controller 108. External actuator 110 may receive
data from controller 108, telling it when to activate one or more
actuators on catheter 102. An ECG device 112 may be activated by
controller 108 and may provide cardiac data to controller 108 which
may be used by controller 108 to operate other components of system
100. Generally, any suitable connectivity and transmission of data,
energy, and the like between any suitable components of system 100
is contemplated within the scope of the present invention.
[0046] The external controller 108 may provide direct user
input/output capabilities, i.e., including screens, printer
interfaces, read/write data storage capabilities, etc. Optionally,
the external controller 108 may require interface with a further
computer, workstation, or other device which interfaces directly
with the user and provides the input/output capabilities. In all
cases, the external controller 108 may provide data input/output
connections shown schematically as line 120.
[0047] Referring now to FIG. 3, catheter 102 for placement in a
heart H may take a variety of forms. Again, for further description
of an exemplary catheter which may be used in the methods of the
present invention, reference may be made to U.S. patent application
Ser. No. 10/734,490, entitled "Method and System for Monitoring and
Treating Hemodynamic Parameters," previously incorporated by
reference. In other embodiments, other catheters may be used and/or
multiple catheters may be used simultaneously or in conjunction.
Catheter 102 may be placed in any suitable location. In FIG. 3,
catheter 102 is shown descending through the aorta into the left
ventricle of the heart H, with sensors both in the aorta and in the
left ventricle. Alternatively, catheter could be placed in the
right side of the heart, sensors could be positioned in multiple
heart chambers, actuators could be placed in the aorta, pulmonary
artery, or inferior vena cava, and/or the like. Thus, although
catheter 102 is shown in the left ventricle and is often described
below in terms of measuring left ventricular function, catheter 102
and system 100 of the present invention may be placed in any
suitable portion of the heart and/or structures surrounding the
heart.
[0048] Catheter 102 may generally include any suitable combination
of sensors and actuators, and the sensors and actuators may be
disposed along catheter 102 at any desired locations. In FIG. 3,
for example, sensors include a flow sensor 130, an electrical
conductivity sensor 131, multiple pressure sensors 132 aligned in a
linear array, an ultrasound sensor 134 comprising a rotated cube
having multiple ultrasound transducers, and a hydrophone 138. Also
included on catheter is an actuator, which may comprise a volume
actuator, pressure actuator or the like. Volume actuators may
include one or more fluid injection ports, one or more fluid
aspiration ports, an inflatable balloon, a combination thereof,
and/or the like. Some embodiments may also include one or more
thermistors.
[0049] Methods of the present invention generally involve inducing
a change in a characteristic of a heart or heart chamber, measuring
the change, and calculating a parameter that changes due to the
measured change. Oftentimes, the changed characteristic will be
either pressure, volume, or both, and the change will typically be
induced by one or more actuators on the catheter. Of course,
multiple changes and/or other types of changes may be induced and
measured, and multiple parameters may be calculated in any given
procedure or method. Such other types of changed characteristics
may include but are not limited to changes in flow, oxygen content,
content of any other suitable gas such as carbon dioxide,
dimensions of a chamber or wall thickness or the like, temperature,
and the like. The calculated parameter (or parameters) will often
provide valuable diagnostic information regarding a patient's heart
function and performance, to allow a physician to make accurate
diagnoses and patient specific treatment decisions, such as whether
to treat a patient pharmaceutically, with device intervention, with
surgery, or with none or some combination thereof.
[0050] In some embodiments, the catheter system is used to measure
various properties of the heart throughout a cardiac cycle,
changing the volume and pressure of a cardiac chamber using
actuation means, and measuring the immediate and cyclical responses
to this change. Some myocardial properties are described by the
response at a single point in time to the actuation means: the
ratio of the change of one parameter over the change of some other
parameter induced by the actuation means. Ventricular compliance,
for example, is the immediate change in ventricular pressure
induced by a change in ventricular volume. Aortic valvular gradient
reserve, a further example, is the change in the maximum aortic
trans-valvular pressure gradient measured at the point of maximum
aortic flow, the change of which results from a modified LVEDP.
Other cardiac properties are described by the cyclical output of
the heart following two different "initial" conditions. In this
context, "initial conditions" is defined as those conditions that
exist in the ventricle (or other heart chamber) at End Diastole,
the point in time when the ventricle begins to contract. Cardiac
Reserve, for example, is the increase in cardiac output induced by
an increase in LVEDP. Similarly, methods of the present invention
may be used to derive the "reserve" of a number of cardiac
properties. In this context, "reserve" describes the change in a
property due to a change in the inducing conditions.
[0051] For example, in one embodiment a catheter may be used to
measure in real-time the pressure and volume of the left ventricle.
The catheter may also be capable of measuring in real-time the
blood flow rate through the aorta. From these measurements the
catheter system can calculate the left ventricular end-diastolic
pressure (LVEDP), left ventricular end-diastolic volume LVEDV, left
ventricular end-systolic pressure LVESP, left ventricular
end-diastolic volume LVESV, cycle time (heart rate), change in
pressure divided by change in time (dP/dt), regurgitation in the
aortic and mitral valves, and/or the ejection fraction of the heart
for each cycle. Based on the data sensed by the catheter, the
system may also calculate, display and record the Pressure-Volume
loop of the left ventricle. An optional right catheter, when used,
allows simultaneous measurements of the right atrial and/or
right-sided ventricular pressure. With these measurements, the
system may be used to determine the pulmonary vascular resistance
(PVR) and the systemic vascular resistance (SVR) for each
cycle.
[0052] Methods of the present invention also typically involve
effecting a change in the volume or pressure in a heart chamber. By
effecting such a change and measuring the change, various cardiac
parameters may be measured in furtherance of accurate cardiac
diagnosis and characterization. In one embodiment, the catheter is
used to add fluid to the ventricle during diastole to increase end
diastolic pressure and volume. Alternatively or additionally, a
balloon placed in the ventricle may be inflated or deflated during
diastole to adjust the end-diastolic pressure and volume. In
another embodiment, a hydrophone transmitter may be used to alter
volume in a heart chamber. An actuator such as a hydrophone may be
used to effect volume changes at a rapid rate, such as 100 or more
times per second. In still other embodiments, the afterload of a
heart may be modified, either in addition to one of the methods
described above or alone. For example, an inflatable balloon
positioned in the aorta may be inflated to increase afterload.
Similarly, preload may be modified, using apparatus such as an
inflatable balloon positioned in the inferior vena cava or right
atrium. Finally, the initial conditions of the heart may be
modified pharmaceutically by injecting various agents into the
blood stream or by exercising the patient through, for example,
lifting saline bags or by generating Preventricular Contractions,
(PVC's) which in general have a lower than usual end diastolic
volume and the cycle immediately following PVC's, which in general
have a higher than usual end-diastolic volume and more vigorous
contraction. This latter method, cardiac response to a PVC,
illustrates the value of the ability to measure stroke volume on a
per-cycle basis. The many suitable methods may be used to effect a
volume and/or pressure change in one or more chambers of a heart,
in order to arrive at useful cardiac parameter data.
[0053] By effecting a change in volume or pressure in a heart
chamber, measuring the change in a parameter that is effected by
the change, and calculating a parameter based on the change,
methods of the present invention may be used to derive novel
parameters that may be used to help characterize a patient's heart
in quantitative terms. By calculating a ratio of the increase in
stroke volume over the increase in end-diastolic pressure, for
example, the system calculates a measure of cardiac reserve. In
another example, a parameter called cardiac amplification may be
measured as the ratio of the increase in stroke volume to the
increase in end-diastolic volume. In yet another example,
continuous measurement of compliance may be obtained by calculating
the ratio of change in pressure caused by a change in volume.
[0054] As discussed above, any suitable combination of sensors may
be disposed along a catheter of the present invention to measure
any of a number of suitable cardiac parameters. For example,
absolute pressure may be measured by one or more sensors. Such
pressure sensors, for example, may have a frequency response of at
least 100 Hz in some embodiments. In one embodiment, at least one
pressure sensor is located near the distal end of the catheter, a
second pressure sensor is located on the catheter to allow the
sensor to be positioned just proximal to the aortic valve (when the
catheter is positioned in the left ventricle), and a third pressure
sensor is located outside the body of the patient to detect
atmospheric pressure. In other embodiments, the third, atmospheric
sensor may be eliminated, atmospheric pressure may be alternatively
measured on the external computation device (the interface "box"),
additional sensors may be added, positions of sensors may be
changed, and/or the like. In some embodiments, for example, one or
more sensors may be used to measure transthoracic pressure, which
changes when breathing, which is particularly important when
diagnosing tamponade, or to measure a finer spatial pressure
gradient across the aortic valve and into the left ventricle, which
is particularly important when differentially diagnosing aortic
stenosis (AS) and hypertrophic obstructive cardiomyopathy (HOCM) as
well as hypertrophic non-obstructive cardiomyopathy (HNOCM).
[0055] Volume measurement in a heart chamber such as the left
ventricle may be accomplished by any of a variety of sensors and
methods. In one embodiment, a sensor comprising six ultrasound
transducers mounted orthogonal to each other is used to measure six
orthogonal radii of curvature of an assumed ovoid shape of the
heart. These measurements may be used to determine multiple
estimates of the ventricular volume at any suitable interval, such
as once every heart cycle or even multiple times per second. An
alternative embodiment uses a phased array ultrasonic system to
measure the cross-sectional area of a heart chamber at multiple
points along it's axis throughout a heart cycle to compute a
measurement of volume using Taylor's theorem. Yet another
embodiment employs the release of a known amount of dye or
electrically conductive liquid, whose concentration is then
measured to estimate the volume of blood into which it was diluted.
A further method involves the measurement of the conductivity of
the blood in the ventricle, commonly referred to as conductance
plethysmography.
[0056] Catheters and systems of the invention can be used to
calculate cardiac output, which may be averaged over a number of
cycles. Such calculations may be made using any suitable method,
such as thermal dilution, dye dilution, conduction dilution, or
Fick's method using oxygen consumption.
[0057] Another parameter which may be measured is blood velocity,
such as blood velocity in the aorta or in one or more pulmonary
arteries. Any suitable measurement method may be used, including
thermal dilution, shear force measurement, a pitot-tube method
(stagnant v. dynamic flow), Doppler ultrasound, or any other
suitable methods, including methods not yet discovered. By
integrating blood velocity throughout a cardiac cycle, the system
may be used to derive a stroke volume for each cycle. Stroke volume
per cycle may then be used, with measured heart rate, to calculate
per-cycle cardiac output. This per-cycle value of cardiac output
may be calibrated using the cardiac output measuring system.
[0058] In many embodiments, a catheter has the ability to modify
the volume and/or pressure in a heart chamber by introducing and/or
removing fluid via actuator 106. In some embodiments, fluid may be
introduced and/or removed during diastole to change the end
diastolic pressure and/or volume. In other embodiments, actuator
106 may rapidly expand or contract or introduce and remove the same
amount repeatedly during an entire cycle of the heart. In some
embodiments, such rapid introductions/removals may occur at a rate
of greater than 100 Hz but less than 1000 Hz, although other rates
are contemplated within the scope of the invention. In one
embodiment, external volume actuator 110, such as a pump, is
coupled with catheter 102 to perform the introduction and/or
removal functions. Altematively, external actuator 110 may perform
introduction or withdrawal of large quantities of fluid to alter
cardiac output, while actuator 106 on the catheter performs a
higher frequency modulation.
[0059] As is discussed above, various embodiments of devices and
methods of the present invention may include any suitable
combination of one or more actuator and one or more sensor. For
example, a catheter that includes one pressure sensor 104 and one
actuator 106, the latter coupled to an external actuator 110, may
be used to measure at least an increase in left ventricular
end-systolic pressure with increasing left ventricular
end-diastolic pressure. This measurement provides one means for
characterizing cardiac reserve, referred to above as pressure
reserve. Thus, the preceding and following descriptions of specific
systems, devices, and/or methods for measuring and calculating
cardiac parameters should not be interpreted to limit the scope of
the invention in any way, but are provided for exemplary purposes
only.
[0060] Actuator 106 may be used to modify the pressure and/or
volume in a heart chamber at one or more precise times during a
cardiac cycle. In one embodiment, actuator 106 provides such
modifications by delivering a fluid (gas or liquid) into or out of
the chamber. Delivery may comprise direct delivery of fluid into
the chamber, such as through one or more apertures in actuator 106.
Alternatively, fluid may be introduced via an inflatable balloon or
similar structure. The timing of fluid deliveries and/or
withdrawals may be coordinated by controller 108, which may use
data from one or more sensors 104, an optional ECG system 112,
and/or the like. The controller 108 may also perform other digital
signal processing, memory, and display functions. A display may be
used to present one or more novel parameters to a doctor or other
user, including but not limited to the various property and reserve
parameters described below.
[0061] In addition to many known cardiac parameters, such as
cardiac output and ventricular pressure, catheter devices and
methods of the present invention provide for measurement of
additional parameters that have not been previously measured. A
table (Table 1) summarizing some of these is presented below.
Others parameters may also be measured or calculated, such as the
inverse of a parameter or the use of the parameter for a specific
chamber or valve. Thus, the following table is not exhaustive.
TABLE-US-00001 TABLE 1 Name Variable Equation Description Left
Ventricle Pressure LVP Measured directly Gauge pressure in Left
Ventricle Left Ventricular Volume LVV Measured directly Volume of
left ventricle End diastolic volume EDV Measured directly Volume of
chamber when volume is maximum End systolic volume ESV Measured
directly Volume of chamber when volume is minimum End diastolic
pressure EDP Direct measurement Gauge Pressure in chamber when
volume is maximum End systolic pressure ESP Direct measurement
Gauge Pressure in chamber when volume is minimum Aortic Pressure
AOP Direct measurement Gauge Pressure in aorta just distal to
Aortic Valve Ejection Fraction EF (EDV-ESV)/EDV Describes the
percentage of blood ejected from a chamber (usually LV) during a
cycle Cardiac Output CO Fick or dilution Total amount of blood or k
* .intg.Velocity * HR pumped by the heart per minute Cardiac Index
CI CO/BSA Cardiac output normalized by Body Surface Area Stroke
Volume SV CO/HR Net amount of blood or ejected into aorta in one k
* .intg.Velocity cycle. Measured either from cardiac output or from
the integral of calibrated blood velocity during a cycle. Stroke
Volume Index SVI SV/BSA Stroke volume normalized by Body Surface
Area Pressure Reserve PR d(LVESP)/d(LVEDP) Marginal change in end
systolic pressure due to a marginal change in end- diastolic
pressure Volume Reserve VR d(LVESV)/d(LVEDV) Marginal change in end
systolic volume due to a marginal change in end- diastolic volume
Cardiac Reserve CR d(CO)/d(LVEDP) Marginal increase in cardiac
output due to a marginal increase in LVEDP Cardiac Reserve Index
CRI d(CI)/d(LVEDP) Cardiac Reserve normalized by Body Surface Area
Stroke Reserve SR d(SV)/d(LVEDP) Marginal increase in stroke volume
due to a marginal increase in LVEDP Stroke Reserve Index SRI
d(SVI)/d(LVEDP) Stroke Reserve normalized by Body Surface Area
Myocardial Work MyW .intg. dV / dt < 0 .times. P .times. .times.
d v - .intg. dV / dt > 0 .times. P .times. .times. d v ##EQU1##
Work performed by myocardial tissue during a single cycle
Myocardial Work Moment MyWM .intg. dV / dt < 0 .times. PV
.times. .times. d v - .intg. dV / dt > 0 .times. PV .times.
.times. d v ##EQU2## Work moment performed by myocardial tissue
during a single cycle Myocardial Work Index MyWI MW/BSA Myocardial
work normalized by Body Surface Area Myocardial Reserve MyR
d(MW)/d(LVEDP) Marginal increase in myocardial reserve due to a
marginal increase in LVEDP Myocardial Reserve Index MyRI
d(MWI)/d(LVEDP) Myocardial Reserve normalized by Body Surface Area
Stroke Work SW SV * ( AOP Systole _ - LVP Diastole _ ) ##EQU3##
Hemodynamic work performed by the left ventricle during a single
cycle Stroke Work Index SWI SW/BSA Stroke Work normalized by Body
Surface Area Stroke Work Reserve SWR d(SW)/d(LVEDP) Marginal
increase in Stroke Work due to a marginal increase in LVEDP Stroke
Work Reserve SWRI SWR/BSA Stroke Work Reserve Index normalized by
Body Surface Area Systolic Ejection Period SEP Direct measurement
Time during which blood is ejected from LV into Aorta Stroke Power
SP SW/SEP Power performed by heart against circulatory system
Stroke Power Index SPI SP/BSA Stroke Power normalized by Body
Surface Area Stroke Power Reserve SPR d(SP)/d(LVEDP) Marginal
increase Stroke Power due to a marginal increase in LVEDP Stroke
Power Reserve SPRI SPR/BSA Stroke Power Reserve normalized by body
surface areas Myocardial Power MyP MyW/SEP Power performed by the
myocardia during systole Myocardial Power Index MyPI MyP/BSA
Myocardial Power normalized by body surface area Myocardial Power
Reserve MyPR d(MyP)/d(LVEDP) Marginal increase in myocardial power
due to a marginal increase in end diastolic pressure Myocardial
Power Reserve MyPRI MyPR/BSA Myocardial Power reserve Index
normalized by body surface area Myocardial Power MyPSV MyP/SV Power
required to deliver Requirement unit stroke volume Ejection
contractility EC P 2 .times. V 2 - P 1 .times. V 1 ( t 2 - t 1 )
.times. .intg. t 1 t 2 .times. Q .times. .times. d t ##EQU4##
Instantaneous power over instantaneous stroke volume (units: dP/dt)
Cardiac Efficiency CE SW/M.sub.YW Efficiency of the heart in
converting myocardial work into circulatory work Cardiac
Amplification CA d(SV)/d(LVEDV) Marginal increase in stroke volume
due to a marginal increase in LVEDV Valvular Gradient VG
.DELTA.Pmax Maximum (during a cycle) pressure gradient across a
valve Valvular Gradient Reserve VGR d(VG)/d(LVEDP) Increase in VG
as a function of increase in LVEDP. Valvular Area VA 0.11 * SV
.DELTA.P Standard calculation of valvular area using mean pressure
gradient and mean flow rate Valvular Area Reserve VAR
d(VA)/d(LVEDP) Increase in valvular area as a function of increase
in LVEDP Valvular Regurgitation VR .intg.Q.sub.REGURGITATION
Cumulative regurgitanT flow during a cycle Valvular Regurgitation
VRR d(VR)/d(LVEDP) Increase in regurgitanT Reserve flow as a
function of increase in LVEDP
[0062] Some of the methods for measuring and calculating cardiac
parameters according to principles of the present invention are
described below. These methods are not an exhaustive list of the
methods which may be employed according to the present invention as
described in the appended claims.
[0063] Exemplary Methods for Determining Left Ventricular
End-Diastolic Pressure (LVEDP), Left Ventricular End-Systolic
Pressure (LVESP), and Aortic Pressure (AOP)
[0064] In one embodiment, catheter 102 maybe used in a left heart
catheterization procedure, and thus measure cardiac parameters
relating to the left ventricle. Other embodiments, however, may be
optimized for other chambers of the heart and, thus, may measure
parameters in one or more of the other three chambers of the heart.
Thus, LVEDP and EDP (End Diastolic Pressure) may be occasionally
used interchangeably in this application, as LVEDP is merely one
example of EDP.
[0065] In one embodiment, LVP (Left Ventricular Pressure) may be
measured using a microfabricated pressure sensor attached to the
catheter and introduced into the left ventricle. In alternate
embodiments, an external pressure sensor is hydraulically linked by
a lumen in the catheter to the body fluids of the left ventricle.
Similarly, AOP is measured in some embodiments using a second
microfabricated pressure sensor attached to the catheter. In
alternate embodiments, AOP may be measured with the first
microfabricated sensor or an external pressure sensor hydraulically
linked to the aorta.
[0066] One method of determining LVEDP is to record left
ventricular pressure (LVP) at point in time when left ventricular
volume (LVV) is at a maximum, that is, just as the ventricle is
about to contract. An alternate method comprises recording LVP at
the "R" wave of the Q-R-S complex of an electrocardiogram (ECG).
Another alternative comprises monitoring the left ventricular
pressure continuously and using a pattern recognition algorithm to
find the pressure when change in pressure divided by change in time
equals zero (dP/dt=0) and d.sup.2P/dt.sub.2 is >0 just before
dP/dt becomes maximum. Still another alternative method for
determining LVEDP is to measure the pressure when the "first" heart
sound "S1" stops, which occurs when the mitral valve is closed. To
obtain the heart sounds, a pressure sensor may be used to sample
the pressure signal at about 2000 times per second (or any other
suitable frequency) and filter out the lower frequency components
associated with increase in blood pressure. Alternatively, the
catheter may employ a dedicated hydrophone for monitoring acoustic
signals emanating from valves, intracaridac defects which produce
shunts, regurgitant lesions or the like.
[0067] One method of determining LVESP is to record LVP when LVV is
at a minimum, which is the point of minimum left ventricular
volume. Another method of determining LVESP is to record LVP when
the blood velocity in the aorta first becomes zero after reaching a
maximum positive number, which is the point at which blood first
stops flowing into the aorta. A significant difference between
these two values might indicate and allow quantification of mitral
regurgitant flow (or flow through shunts to the right side) after
the aortic valve closes. An alternative method would be to record
LVP when the "T" wave on the ECG has just ended. The pressures
measured these three ways should give nearly identical results;
therefore a comparison of any differences might help indicate a
physiological abnormality. Another alternative method involves
calculating a regurgitant fraction.
[0068] Method for Determining Left Ventricular End-Diastolic
Volume
[0069] One currently used method for determining LVEDV employs one
or more x-ray images of the heart and a manual drawing of the
ventricular perimeter using an electronic cursor. These outlines
are then used in conjunction with an empirical estimating formula
to calculate an estimate of the heart's volume at end diastole.
This technique is cumbersome and time consuming, making it
impractical for estimating numerous end-diastolic volumes. In
addition, since only one or two projections of the heart are used,
a significant error is implied in the measurement. Furthermore, the
formulae used in such techniques for calculating volume do not
accurately reflect true volume.
[0070] Another currently available technique uses an external
ultrasound transducer to image the whole heart and also measure
volume. This is a fairly accurate technique, but since the
ultrasound transducer is outside the body, it is incapable of
simultaneously measuring pressure or changing end diastolic
pressure. In addition, not all patients have anatomy which is
amenable to an ultrasonic imaging system transthoracically.
Nevertheless, this approach could be used in conjunction
(simultaneously) with a catheter that doesn't feature the
volume-measuring capability.
[0071] In one embodiment of the present invention, a method of
measuring volumes in body cavities such as a heart chamber,
involves using six ultrasound transducers mounted orthogonally to
each other, as shown in FIG. 10. Two of the transducers are mounted
parallel to the catheter and thus measure a distance perpendicular
to the axis of the catheter. The other four transducers are mounted
in pairs on surfaces that are axially 90 degrees rotated from the
first pair of sensors but also tilted 45 degrees up or down. Thus,
the latter four transducers measure the distance between them and
the wall of a heart chamber in four directions which are all
orthogonal to each other. Another way of describing the arrangement
is that of six transducers each mounted on a face of a cube. The
cube is then rotated 45 degrees about one of the faces and mounted
over a catheter body. To facilitate manufacturing of the catheter
while keeping a slim profile, the cube may be "disassembled," i.e.,
the transducer pairs are not necessarily contiguous. The transducer
assembly might also be part of an inflatable or expandable assembly
to project into the ventricle somewhat during measurement.
[0072] An alternative method for measuring ventricular volumes is
to use a phased array ultrasonic imaging system with circular
electrodes, i.e. rings about the catheter. These rings may be
excited slightly out of phase with each other to send the wave up
or down relative to the perpendicular of the catheter. The signals
returning to the rings would be distributed over time, depending
upon the distance from the catheter to the ventricular wall in the
various segments of the ring. Thus, the amplitude over time of the
reflected signal would correspond to the various radial distances
between the catheter and the wall of the heart chamber. Making
numerous measurements at various angles from normal in a very short
period, the system makes multiple cross-sectional area measurements
of the ventricle that are then added using Taylor's method for
estimating volumes (similar to what is done using external
ultrasonic arrays). Yet a third method of measuring ventricular
volumes would be to use two pairs of planar phased array sensors,
each parallel pair perpendicular to the other, so that four sides
of a catheter are mounted with a phased array transducer. Each of
the sensors may, as above, measure a distance to the wall in order
to measure, at any given angle from the transducers, four radii to
the ventricular wall. Taylor's method is then used as before to
estimate true ventricular volume.
[0073] One method of estimating LVEDV is to record LVV, measured
using one of the above methods, at the point of time when it is at
a maximum. In an alternative method, an array of electrical
conductance sensors on the catheter is used to determine the
average conductance of the ventricular blood. A volume of liquid
with a known and different electrical conductivity is dispersed
into the left ventricle during diastole. At end diastole and during
systole, the conductivity in the ventricle is monitored. These
measurements produce an estimate of the diluted electrical
conductance of the ventricular blood. Then, knowing the volume of
injected blood (V.sub.I), the electrical conductance of the
injected blood (k.sub.I), the conductance of the undiluted blood
(k.sub.B), and the conductance of the diluted blood (k.sub.D), one
may compute the end diastolic volume using the following equation:
V D = V I .times. k I - k B k D - k B ##EQU5##
[0074] Another method of estimating end diastolic volume uses an
array of temperature sensors on the catheter to determine the
temperature of the blood. A quantity of blood at a lower
temperature is injected into the ventricle during diastole. The
temperature of the diluent may be measured just before it leaves
the catheter, to improve accuracy. Then, knowing the volume of
injected blood (V.sub.I), the specific heat of the blood (C.sub.B),
the specific heat of the diluent (C.sub.I), the undiluted
temperature of blood (T.sub.B), the temperature of the diluent
(T.sub.I), and the average temperature of the diluted blood at end
diastole (T.sub.D), the end diastolic volume (V.sub.D) is given by
the following equation: V D = V I .function. ( 1 + C I .function. (
T D - T I ) C B .function. ( T B - T D ) ) ##EQU6##
[0075] In another embodiment, a method of estimating end diastolic
volume uses an array of light sources and optical sensors, perhaps
incorporating optical fibers. A volume of a solution containing a
dye of a known concentration is injected and dispersed into the
ventricle during diastole. The concentration of dye in the blood
may be measured using either absorption or fluorescent techniques.
A dye may be any marker, such as a liquid, gas, other fluid or the
like. A fluorescent technique, for example, would entail shining
light of one wavelength into the blood and detecting the intensity
of light at a different (fluorescent) wavelength. The concentration
of dye in the blood would be a linear function of the ratio of the
intensity of the fluorescent light over the intensity of the
exciting light. Then, knowing the volume of injected blood
(V.sub.I), the concentration of dye in the undiluted blood
(D.sub.B), the concentration of dye in the diluent (D.sub.I), and
the average concentration of dye in the diluted blood at end
diastole (D.sub.D), the end diastolic volume (V.sub.D) is given by
the following equation: V D = V I .times. D B - D I D B - D D
##EQU7##
[0076] In other embodiments, it may be useful to determine an
end-diastolic volume without introducing fluid to the ventricle. In
some embodiments, it may even be useful to reduce the end-diastolic
volume or end-diastolic pressure from the resting value. To
accomplish this, a catheter may include a balloon that can hold at
least as much volume as the diluent (either thermal, conductive, or
dye diluent or none if ultrasound is used to measure volume, as in
the preferred method). The balloon is first inflated in the
ventricle during the systolic phase of the previous cycle, helping
to eject a corresponding amount of blood from the ventricle. To
determine the end-diastolic volume without influencing it, the
balloon is simultaneously and completely deflated during diastole
by a volume equal to the volume of diluent injected into the
ventricle at the same time. Thus, as the balloon shrinks, the
diluent is added to the ventricle without increasing or decreasing
the pressure in the ventricle. It may be useful to decrease the
end-diastolic volume and/or end-diastolic pressure from an at-rest
state while determining the end-diastolic volume. This may be
accomplished by first inflating the balloon during the systolic
phase or, in the case of repeated cycles, just after the aortic
valve has closed. Then, during diastolic filling of the ventricle,
an amount of diluent is dispersed into the ventricle. The balloon
is simultaneously and completely deflated by a volume greater than
the volume of diluent added, reducing the end diastolic pressure
and volume. The end-diastolic volume is determined using one of the
dilution methods described above. In one embodiment, one or more
ultrasound transducers are used to measure the ventricular volume
continuously while the balloon is inflated during systole and
deflated in diastole to reduce the end-diastolic pressures and/or
volumes.
[0077] Methods for Determining End-Systolic Volume
[0078] One method for measuring LVESV is to record LVV when it is
at a minimum, using one of the continuous volume measuring systems.
An alternative method for measuring for LVESV is that LVV when
aortic flow rate is first zero following its maximum. The
difference in volumes of these two recordings is equal to the
combination of mitral regurgitant flow and left-to-right shunt flow
after the aortic valve is closed.
[0079] Methods for Determining Ejection Fraction
[0080] Ejection Fraction is typically defined as the ratio of the
difference between end-diastolic volume and end-systolic volume
over end-diastolic volume. This calculation may be made, using any
of the above-described methods of measuring EDV and ESV.
[0081] Methods for Determining Cardiac Output Cardiac Index, Stroke
Volume, and Stroke Volume Index on a Per-Stroke Basis
[0082] In one embodiment, a blood velocity or flow rate sensor is
coupled with the catheter and inserted into the aorta. This sensor
samples the velocity of blood at regular intervals, such as
approximately once every millisecond, and transmits that
information to a controller or other processor. The controller then
determines the average blood velocity by averaging the readings
taken over a second (or some other similar period of time that is
representative of the next step). During that sampling time, the
cardiac output is independently measured using one of the accepted
methods, such as Fick's Law using oxygen consumption or a dilution
method (thermal dilution, conductance dilution or dilution with a
marker, such as a gas, other fluid, liquid, dye or the like).
(Grossman's Cardiac Catheterization and Angiography, pp. 101-117
describes these methods in detail). The cardiac output thus
measured is divided by the average velocity or flow rate to
determine a scaling coefficient. This coefficient assumes that the
aortic cross section near the velocity or flow rate sensor is
reasonably constant during the sampled cycle and successive cycles.
A number of different methods of measuring blood velocity or flow
rate are possible, including thermal dilution, shear force
measurement, a pitot-tube method (stagnant versus dynamic flow),
Ultrasound Doppler, and/or any other suitable method. Once the
scaling factor has been determined, the stroke volume may be
determined for any given cycle and is equal to the product of the
scaling factor and the integral of velocity through that cycle. The
stroke time is also calculated as that period between successive
end-diastolic events. Cardiac output is then calculated as the
ratio between stroke volume over stroke time, adjusted to correct
units. Cardiac index is cardiac output divided by body surface area
(BSA), which is a known value based on a patient's height and
weight. Stroke volume index is stroke volume divided by BSA.
[0083] Methods for Determining Cardiac Reserve and Cardiac Reserve
Index
[0084] In one embodiment, a method for measuring cardiac reserve
involves first measuring LVEDP and/or LVEDV at the beginning of one
cardiac cycle and then measuring the cardiac output during that
cycle using the methods described above. This measurement may be
repeated any number of times and multiple data pairs (LVEDP, CO)
may be taken. Then, an amount of fluid is injected into the left
ventricle during a diastole period and the resulting end-diastolic
pressure recorded. The cardiac output for that cycle is recorded
using the methods described above and a new data point (LVEDP, CO)
is recorded. This process is repeated as desired to create a set
(n>=2) of data pairs. A line of regression is then fit through
the data points using a least-squares technique. The slope of that
line is equal to cardiac reserve. Cardiac reserve index is equal to
cardiac reserve divided by BSA.
[0085] Methods for Determining Stroke Reserve and Stroke Reserve
Index
[0086] One method of measuring cardiac reserve is to first measure
the LVEDP and the beginning of one cardiac cycle and then measuring
stroke volume during that cycle using the methods described above.
This measurement may be repeated any number of times and multiple
data pairs (LVEDP, SV) taken. Then, an amount of fluid is injected
into the left ventricle during a diastole period and the resulting
end-diastolic pressure recorded. The stroke volume for that cycle
is recorded using the methods described above and a new data point
(LVEDP, SV) is recorded. This process is repeated as desired to
create a set (n>=2) of data pairs. A line of regression is then
fit through the data points using a least-squares technique. The
slope of that line is equal to stroke reserve (SR). Stroke reserve
index (SRI) is equal to SR divided by BSA.
[0087] Methods for Determining Myocardial Work, Myocardial Work
Index, Myocardial Work Reserve, and Myocardial Work Reserve
Index
[0088] Myocardial work (M.sub.YW) comprises the work performed by
the myocardium against the blood in the heart during a single heart
cycle. It is mathematically defined as the integral of Pressure and
dV as V varies from V(max) to V(min) minus the integral of Pressure
and dV as V varies from V(min) to V(max). Thus it is the work
performed by the heart tissue during systole minus the work
performed on the heart tissue by the body during diastole.
Myocardial work may thus be expressed as the difference between the
integral of the pressure and volume while the volume is decreasing
from the integral of the pressure and volume while the volume is
increasing: SW = .intg. d V / d t < 0 .times. P .times. d v -
.intg. d V / d t > 0 .times. P .times. d v ##EQU8## Myocardial
work index (MWI) is equal to the myocardial work divided by
BSA.
[0089] In some embodiments, it may also be advantageous to
calculate the first moment of work, which could also be useful for
optimization. The first moment of work is calculated as: SW =
.intg. d V / d t < 0 .times. PV .times. d v - .intg. d V / d t
> 0 .times. PV .times. d v ##EQU9## Myocardial work index (MWI)
is equal to the myocardial work divided by BSA.
[0090] In one embodiment, myocardial work reserve is calculated by
first recording the LVEDP of a given heart cycle and then
calculating the myocardial work during that cycle. This measurement
may be repeated any number of times and multiple data pairs (LVEDP,
M.sub.YW) taken. Then, an amount of fluid is injected into the left
ventricle during a diastole period and the resulting end-diastolic
pressure recorded. The myocardial work for that cycle is recorded
using the methods described above and a new data point (LVEDP,
M.sub.YW) is recorded. This process is repeated as desired to
create a set (n>=2) of data pairs. A line of regression is then
fit through the data points using a least-squares technique. The
slope of that line is equal to Myocardial reserve (M.sub.YR).
Myocardial reserve index (MRI) is equal to myocardial reserve
divided by BSA.
[0091] Methods for Determining Stroke Work, Stroke Work Index,
Stroke Work Reserve, Stroke Work Reserve Index, and Cardiac
Efficiency
[0092] Stroke work (SW) is typically defined the work performed by
the left ventricle on the circulatory system. This relationship is
displayed in graphic form in FIGS. 4A and 4B. In one embodiment of
the present invention, stroke work is determined by calculating the
integral of the product of volume ejected into the aorta and
pressure increased by the ventricle. In some embodiments, the
average filling pressure is determined and subtracted from the
ventricular pressure during systole. This difference is then
multiplied by the quantity of blood flowing into the aorta. This
product is then integrated over a single stroke to calculate stroke
work. SW = .intg. cycle .times. V Aorta .function. ( P systole - P
diastole _ ) ##EQU10##
[0093] Thus, SW is distinguishable from myocardial work. The
difference between these two parameters involves a difference in
how regurgitant flow plays into the measurements. Myocardial work
measures the work that the heart muscle performs, while SW measures
the work the heart performs against the circulatory system. Cardiac
efficiency (CE), yet another parameter which may be measured
according to the present invention, is defined as the ratio of SW
over myocardial work and is a measure of the efficiency with which
the heart converts myocardial work into stroke work. This parameter
may be used, for example, by biventricular pacing devices,
pharmaceutical intervention, and other interventions to optimize
their performance.
[0094] In an alternative embodiment, stroke work may be calculated
by taking the integral of the product of aortic pressure and aortic
flow rate minus the integral of the product of left atrial pressure
and flow through the mitral valve. With either of the two methods
described above, the stroke work index is equal to stroke work
divided by BSA. A similar set of calculations is possible for the
right ventricle, where stroke work would be the integral of the
product of the pressure in the Pulmonary Artery times the systolic
volume flowing into the Pulmonary Artery minus the integral of the
right atrial pressure times the diastolic volume flowing into the
right ventricle.
[0095] In some embodiments, stroke work reserve is calculated by
first recording the LVEDP of a given heart cycle and then
calculating the stroke work during that cycle. This measurement may
be repeated any number of times and multiple data pairs (LVEDP, SW)
taken. Then, a predetermined amount of fluid is injected into the
left ventricle during a diastole period and the resulting
end-diastolic pressure recorded. The stroke work for that cycle is
recorded using the methods described above and a new data point
(LVEDP, SW) is recorded. This process is repeated as desired to
create a set (n>=2) of data pairs. A line of regression is then
fit through the data points using a least-squares technique. The
slope of that line is equal to stroke work reserve (SWR). Stroke
work reserve index (SWRI) is equal to SWR divided by BSA.
[0096] Methods for Determining Cardiac Amplification
[0097] Cardiac amplification (CA) may be defined as the marginal
increase in stroke volume due to a marginal increase in
end-diastolic volume. In one embodiment, cardiac amplification is
calculated by first recording the LVEDV of a given heart cycle and
then calculating the stroke volume during that cycle. This
measurement may be repeated any number of times and multiple data
pairs (LVEDV, SV) taken. Then, an amount of fluid is injected into
the left ventricle during diastole and the resulting end-diastolic
volume is measured. The stroke volume for that cycle is measured
using the methods described above and a new data point (LVEDV, SV)
is recorded. This process is repeated as desired to create a set
(n>=2) of data pairs. A line of regression is then fit through
the data points using a least-squares technique. The slope of that
line is equal to cardiac amplification.
[0098] Methods for Determining Valvular Gradient, Valvular Gradient
Reserve, Valvular Area, Valvular Area Reserve, Valvular
Regurgitation, Valvular Regurgitation Reserve, and Valvular
Resistance
[0099] In one embodiment, valvular pressure gradient (VG) may be
measured directly using two pressure sensors one upstream and the
other downstream of a heart valve, as in the aortic valvular
pressure gradient. In another embodiment, VG may be measured
somewhat indirectly, as in the case of the mitral valve, where
upstream pressure may be measured using a known pulmonary capillary
wedge pressure measurement technique and downstream pressure is
measured in the left ventricle. In either case, a pressure gradient
across a valve may be measured throughout the appropriate filling
period while the flow through the valve is simultaneously
determined. In the case of an aortic valve, the flow through the
valve is measured using the aforementioned scaled velocity sensor
in the aorta; in the case of the mitral valve, the flow is measured
as the diastolic change in ventricular volume minus any regurgitant
aortic flow measured by the scaled velocity sensor in the aorta.
Throughout the filling period, multiple data pairs are recorded in
the form of (.DELTA.P, Q), where .DELTA.P is the pressure gradient
and Q is the instantaneous volumetric flow rate through the valve.
The maximum pressure gradient (.DELTA.P) and mean pressure gradient
during any cycle may then be recorded as the VG for that cycle.
[0100] The total regurgitant flow through the valve in a
cycle--valvular regurgitation (VR) may be calculated as the
integral of the reverse volumetric flow rate during a cycle. In the
case of aortic, pulmonic or tricuspid regurgitation, this flow may
be directly determined using the output of the scaled velocity
sensor, and is the scaled integral of all negative volumetric flow
rates during a cycle. In the case of the mitral valve, regurgitant
flow may be determined by subtracting the stroke volume (measured
in the aorta using the scaled velocity sensor) from the difference
between the maximum and minimum left ventricular volumes
(LVEDV-LVESV). Thus mitral regurgitant flow, in the absence of
shunts, is equal to LVEDV-LVESV-SV. In some embodiments,
measurement of mitral regurgitation may include factoring in any
aortic regurgitation that is present. Since calculating stroke
volume includes subtracting regurgitant (diastolic) aortic flow
from the total amount of blood ejected into the aorta during a
given cycle, in some embodiments the amount of aortic regurgitation
is added back in to give a more accurate measurement of mitral
regurgitation. Therefore, MR=LVEDV-LVESV-SV+AR, where MR is the net
systolic mitral regurgitant flow, and AR is the net (diastolic)
aortic regurgitant flow.
[0101] To calculate the effective area of a valve, one embodiment
uses a known formula (the Gorlin Formula--see Grossman's Cardiac
Catheterization and Angiography, p143). Using the known formula,
average flow rates such as cardiac output and mean pressure
gradients are used to calculate a mean orifice area So, this
embodiment uses these mean values to calculate the effective
valvular area. The equation for mean mitral valve area ( MMVA )
.times. .times. is .times. .times. CO / ( HR * DFP ) ( 44.3 * 0.85
) .times. .DELTA. .times. .times. P , ##EQU11## where CO is Cardiac
Output in cc/min, HR is beats/min, DFP is filling period in
seconds/beat, and .DELTA.P is the mean pressure gradient across the
mitral valve in mm Hg. This technology enables the real time
estimate of valvular area by using instantaneous measures of flow
rate and pressure gradient. Thus mitral valve area ( MVA ) .times.
.times. is .times. .times. Q ( 44.3 * 0.85 ) .times. .DELTA.
.times. .times. P , ##EQU12## where Q is the volumetric flow rate
through the valve at any point in time and .DELTA.P is the pressure
gradient at approximately the same point in time. (This pressure
gradient is typically measured with the assistance of a right heart
catheter and is the difference between the pulmonary capillary
wedge pressure from the left ventricular pressure). With this
equation--modified from Gorlin and Gorlin's original--it is
possible to measure orifice diameter as a function of time.
[0102] A similar equation is found for the aortic valve: mean
aortic valve area ( MAVA ) .times. .times. is .times. .times. CO /
( HR * SEP ) ( 44.3 ) .times. .DELTA. .times. .times. P , ##EQU13##
where SEP is the Systolic Ejection Period and .DELTA.P is this time
the pressure gradient across the aortic valve. Similarly, a real
time measurement of aortic valve area ( AVA ) .times. .times. is
.times. .times. Q ( 44.3 ) .times. .DELTA. .times. .times. P ,
##EQU14## where Q is the instantaneous volumetric flow rate through
the aortic valve, as measured using the scaled velocity sensor in
the aorta and .DELTA.P is the pressure gradient across the aortic
valve.
[0103] In one embodiment, variations in the above-described
parameters (regurgitant flow, valvular area, and pressure gradient)
with increasing cardiac output, are measured. One method for
measuring such variations comprises first measuring LVEDP for a
given heart cycle. At the completion of that cycle, additional
parameters related to a valve are measured--for example, valvular
regurgitation(VR), valvular area (VA), and valvular pressure
gradient (VG). Any number of these cycles may be recorded, so that
multiple measurements may be averaged together. On a successive
cardiac cycle, an amount of fluid is introduced into the left
ventricle during diastole to increase end-diastolic pressure and
the resultant values are again measured, typically (but not always)
with a higher cardiac output (resulting from the higher LVEDP).
Multiple data sets are thus generated. To obtain the valvular
gradient reserve (VGR), a least squares method is used to fit a
line is fit between the multiple data pairs (LVEDP, VG). The slope
of that curve is VGR. As cardiac output doubles, the pressure
gradient should quadruple, so VGR would be expected to increase
with increasing cardiac output. It nevertheless represents the
marginal increase in gradient with increasing LVEDP within the
corresponding range of LVEDP.
[0104] In various embodiments, valvular area reserve (VAR) may be
obtained by using a least squares method to fit a line between the
various data pairs (LVEDP, VA). The slope of that fit line is VAR,
which represents the marginal increase in valvular area due to a
marginal increase in LVEDP. There are some patient populations
(some disease states) where the effective area decreases with
increasing cardiac output, and this value would be negative for
that class of patient.
[0105] Similarly, valvular regurgitation reserve (VRR) may be
obtained by using a least squares method to fit a line between the
various data pairs (LVEDP, VR). The slope of this line is VRR,
which represents the marginal increase in valvular regurgitation
due to a marginal increase in LVEDP. Any of these "reserve"
measurements could be made relative to cardiac output (or LVEDV, or
any other variable), instead of LVEDP.
[0106] Methods for Generating Frank-Starling Curves
[0107] A Frank-Starling (F-S) curve has many definitions in the
literature. They all generally relate to the change in hemodynamic
output of the left ventricle due to changes in the left ventricular
end-diastolic volume (LVEDV) or left ventricular end-diastolic
pressure (LVEDP). The most common types of F-S curves are: Cardiac
Output v. LVEDP, Cardiac Output v. LVEDV, Stroke Work v. LVEDP,
Stroke Work v. LVEDV, and LVESP/LVEDP v. LVEDV.
[0108] In some embodiments, an F-S curve places Cardiac Output (CO)
on a vertical axis and LVEDP on a horizontal axis. The catheter
system records the LVEDP at the beginning of one or more heart
cycles and then calculates the CO at the end of each corresponding
cycle. By introducing and/or removing fluid (or increasing or
reducing the volume of an inflatable balloon), the system adjusts
the end-diastolic pressure to a new value and measures that value.
It then calculates the resulting cardiac output for that cycle. By
repeating this process over several cardiac cycles, each using a
different LVEDP as it's starting point, a graph of CO v. LVEDP is
generated, recorded, and displayed to be seen by the physician.
[0109] In other embodiments, an F-S curve that represents Cardiac
Output v. LVEDV may be generated. Any of the above-described
methods may be used for measuring CO on a per stroke basis and
LVEDV on a per stroke basis. Then, by introducing and/or
withdrawing amounts of fluid from the ventricle during diastole,
one may vary the LVEDV for one or more cycles of the heart. If a
reduced starting volume of the heart is desired, for example to
simulate a reduction in preload, a balloon may be attached to the
catheter and inflated during the systolic phase of the previous
heart cycle. The balloon is then deflated during diastole to
simulate a reduction in preload.
[0110] Another variation of an F-S curve is to have either
myocardial work (MyW) or stroke work (SW), both defined above, on
the vertical axis and LVEDP on the horizontal axis. The difference
between the two measures is an important indicator of valvular
disease related to the left ventricle. In a manner similar to that
described above for CO v. LVEDP, the system may be used
simultaneously calculate MyW and SW for each LVEDP. Cardiac
efficiency (CE), the ratio of SW over MyW, may also be calculated
and displayed, showing how the efficiency of the heart changes at
increasing levels of LVEDP and perhaps correspondingly increasing
levels of cardiac output. Any of the above-described parameters may
be plotted against any other suitable parameter or parameters, as
desired.
[0111] In one embodiment, to generate a CO v LVEDP curve, a
real-time cardiac output sensor is coupled with the catheter so
that it resides in the aorta. This real time sensor may be
calibrated using one or more of several accepted methods of
measuring cardiac output, such as Fick's method based on oxygen
consumption or the dilution method. The CO sensor may be used to
measure the volume of blood ejected from the left ventricle during
each cycle. At the same time, another sensor on the catheter
measures pressure inside the left ventricle. During diastole, the
catheter system introduces saline or other fluid into the left
ventricle and measures the resulting LVEDP. Then, as the heart
completes its cycle, the CO sensor measures the output of the heart
during that cycle. The result represents a single point on the CO v
LVEDP curve. After some period of time, a second point is plotted
on the curve by injecting a second bolus of saline or other liquid
into the left ventricle during diastole. The cardiac output and
LVEDP are then measured for that cycle and the second point is
plotted. Additional points are generated during successive cycles
and as various LVEDP conditions are created, as desired.
[0112] In another embodiment, an F-S curve based on a different
definition of stroke work is generated using a method similar to
the one just described. Stroke work is calculated simultaneously
(or nearly simultaneously) with cardiac output (i.e. during the
same cycle). One definition of stroke work which may be used is the
integral of the product of pressure and stroke volume during a
single cycle. Another definition uses the change in volume of the
ventricle to determine the work performed by the heart. This latter
measurement, however, includes work required to pump regurgitant
flow retrograde against the mitral valve as well as work lost to
regurgitant aortic flow. In an additional embodiment, the stroke
work is the product of the volume of blood ejected into the aorta
multiplied by the pressure gradient between the ventricle and the
aorta. The volume of blood ejected into the aorta is measured by
the blood velocity sensor and the pressure gradient is measured
using the difference between two pressure sensor, one in the
ventricle and the other in the aorta near the velocity sensor.
[0113] As previously discussed, catheters in many embodiments of
the present invention include means for effecting end-diastolic
pressure and/or volume by introducing and/or withdrawing an amount
of fluid (such as saline, glucose, or any other suitable fluid)
into or from the ventricle at a desired time during a heart cycle,
such as during diastole. In one embodiment, fluid introduction is
achieved by driving an external actuator, such as a pump, coupled
with the catheter using control signals from the controller, such
as a computer or other data processor. The timing of fluid
introduction and/or withdrawal may be based upon measurements taken
via a pressure sensor in the heart chamber. Such measurements may
be taken at any suitable interval, but in some embodiments they are
taken at a rate of about 1000 Hz.
[0114] Methods for Generating Pressure/Volume Loops
[0115] With reference now to FIGS. 4-9, information which may be
generated and optionally displayed according to one embodiment of
the invention is shown. This information is generally referred to
as "pressure-volume loops," and such information may be displayed
in various forms. In one embodiment, a catheter is used to generate
pressure-volume loops by measuring on a simultaneous or
near-simultaneous basis intracavitary pressure and volume. The
volume may be measured, for example, using six orthogonally
oriented ultrasound transducers, as described in detail above.
Referring to FIGS. 10 and 11, one embodiment of such a
six-transducer device 162 on a catheter 102 is shown. As designated
by the arrows in FIG. 11, the six transducers may be used to
measure six distances from the transducer device 162 to various
locations on the inner wall of the heart chamber. These six
distances represent radii of curvature to an inscribed ovoid. One
or more phased array transducers may alternatively be used to
measure volume. In one embodiment, multiple phased array
transducers have at least two arranged axially about the axis of
the catheter. In another embodiment, four phased array sensors are
arranged axially around the catheter.
[0116] Pressure may be measured using readings from one or more
pressure sensors located inside the cavity (i.e., the left
ventricle in FIG. 11, but any other suitable heart chamber or other
cavity is contemplated). In some embodiments, the pressure sensor
used in the heart chamber comprises an absolute pressure sensor, so
that a pressure sensor sampling the ambient pressure is often used
as well, to enable the calculation of a gauge pressure with which
most physicians are familiar. This gauge intracavitary pressure
comprises the absolute intracavitary pressure minus the absolute
ambient pressure. In various embodiments, an ambient absolute
pressure sensor may be coupled with the catheter outside of the
body or, alternatively or additionally, may be coupled with a
controller, a console, and/or the like.
[0117] Referring now to FIGS. 5A and 5B, one method of the present
invention involves introducing fluid (or inflating an expandable
balloon) inside a heart chamber such as the left ventricle during
diastole to cause a shift in a pressure/volume loop. The original
loop is shown as the points a, b, and c, while the shifted loop (up
and to the right) is shown as points a', b', and c'. Generally,
introducing a fluid into the left ventricle during diastole may
result in a different end-diastolic pressure and/or volume, which
may be measured and shown graphically as a shifted pressure/volume
curve.
[0118] By introducing and/or withdrawing fluid into/from the
ventricle during diastole, various end-diastolic pressure and
volume conditions for the ventricle are created. The resulting
pressure and volume of the ventricle may then be measured
continuously as the heart completes its cycle. The integral of
pressure multiplied by volume (as measured during one heart cycle)
is equal to the stroke work, as shown by the area inside the curve
in FIG. 5A and on the vertical axis in FIG. 5B. Stroke work as a
function of end diastolic pressure is one measure of ventricular
performance. Pressure/volume loops, as in FIGS. 4A and 5A, may be
used to generate Frank-Starling curves, which may include any of a
number of various parameters, as described in detail above. This is
a vast improvement over conventional methods for generating
Frank-Starling curves, which involve measurements taken over a
period of days using a Swan-Ganz catheter to measure cardiac
output, as well as administration of one or more medications to
vary the LVEDP.
[0119] Referring again to FIGS. 5A and 5B, in some embodiments of
the invention, methods may be used to calculate myocardial
stiffness and/or compliance of the heart chamber in which a
catheter is positioned. In one embodiment, a method of calculating
myocardial stiffness involves first measuring pressure and volume
when volume is at a maximum (i.e., at end of diastole) and then
again when volume is at a minimum (i.e., end of systole). During a
subsequent heart cycle, end-diastolic pressure and volume are
increased (or decreased) using one or more actuator on the
catheter, and the two sets of data points are recorded again. Any
suitable number of such pairs of data points may be measured, and
they may then be used to generate a pressure/volume curve. A least
squares routine may then be used for each set of data pairs (i.e.,
the end-diastolic set and the end-systolic set) to fit a straight
line between each set of points. The slope of the line through the
end-diastolic points is the lusitropic stiffness of the heart, and
the inverse of that slope is the lusitropic compliance. The slope
of the line through the end systolic points is the inotropic
stiffness and the inverse of that slope is the inotropic
compliance. These measurements and equations used for calculations
are shown as labels on FIG. 5A.
[0120] In another embodiment, a method of measuring the compliance
of a heart chamber involves continuously varying the volume in the
chamber and simultaneously measuring pressure in the chamber to
give a continuous measure of chamber wall stiffness. In this
method, a hydrophone may be used to vary the volume inside the
ventricle at any suitable frequency, such as approximately 200
times per second. A pressure sensor is used to measure pressure
change at approximately the same frequency at which it is being
effected by the hydrophone. By filtering the pressure signal at 200
Hz, one obtains a signal whose amplitude is proportional to the
stiffness of the heart throughout the cycle. The inverse of this
number is the compliance of the heart throughout the cycle. When
either valve to the ventricle is open, the method measures the
effective stiffness and compliance of the hydraulically linked
chamber. Thus, when the mitral valve is open, the stiffness and
compliance of both the left atria and the left ventricle, as well
as some of the pulmonary vein, may be measured. When the mitral
valve is closed and the aortic valve is open, the combined
stiffness of the left ventricle and the aorta may be measured. When
both valves are closed, as in isovolumic contraction or isovolumic
relaxation, then the stiffness of the left ventricle alone may be
measured. Since the pressure/volume slope is rather steep during
either isovolumic phase, it may be desired to use a higher
frequency such as 1000 Hz or even 5000 Hz to measure stiffness and
compliance and how those values change during contraction or
relaxation.
[0121] FIGS. 6-9 show various ways in which changes in pressure,
and thus stiffness, may be displayed over a period of time. FIG. 6
shows a change in pressure when an actuator is used to effect an
oscillating volume change. FIG. 7 shows the same change, after
being processed through a low-pass filter. FIG. 8 shows the same
change, after being processed through a high-pass filter. Finally,
FIG. 9 shows the same data as it relates to systolic and diastolic
stiffness of the heart chamber.
[0122] Methods for Determining Dose/Response Characteristics of
Medications
[0123] In yet another embodiment, a method of the present invention
may be used to measure one or more dose/response characteristics of
a medication on various cardiac and/or circulatory functions.
Because most patients have somewhat unique responses to a given
medication, knowing the dose/response curve of any medication
allows for a quantitatively based selection among similar
medications, quantitative prediction of optimal dosing levels of
the chosen medication, and quantitative comparison of the short
term effects of combinations of medications.
[0124] In one embodiment of the invention, a method involves
administering a nitrate-type medication to a patient in small,
increasing doses, while one or more various hemodynamic parameters
and performance ratios are monitored. Measured parameters may then
be plotted on one axis of a graph, while the dose concentration of
the medication is plotted on the opposing axis. For example,
Cardiac Reserve (CR) (y-axis) as a function of nitrate dose
(x-axis) may be plotted. A three dimensional plot may be used to
express, for example, Cardiac Reserve (z-axis) against LVEDP
(x-axis) and Nitrate Dose (y-axis), where the x, y, and z axes are
isometrically presented as if a corner of a cube.
[0125] In a further example, a new "set point," or optimal
hemodynamic parameter set for a patient, may be produced by some
combination of medications at concentration levels determined
during the catheterization. (For example, the LVEDP may be lowered
to some value, the cardiac output may be increased to some value,
and the SVR may be lowered to some value, each of which is expected
to have a therapeutic benefit.) The patient could then be given a
"prescription" using similar-acting oral medications to maintain
that set point long after the catheterization has ended.
[0126] In a further example, the catheter may be placed in the
aorta, where the stiffness and compliance of the aorta may be
directly measured. This type of measurement might be used before
and after a drug treatment (for example, EDTA may be infused into
the femoral vein) to test the effectiveness of that medication in
increasing aortic compliance. Similarly, the catheter may be placed
in the left ventricle and the patient given an inotropic agent
whose purpose is to modify the compliance of the ventricle. Without
changing the end diastolic pressure, the effect of the medication
on ventricular compliance as a function of dosing levels may be
directly measured, recorded and displayed.
[0127] Although the foregoing description is a complete and
accurate description of the invention, it is offered for exemplary
purposes only and should not be interpreted to limit the scope of
the present invention as it is defined in the claims. Various
changes, additions, substitutions, and/or the like may be made to
many of the methods, devices, and systems described above, without
departing from the scope of the invention as claimed. For example,
in some embodiments one or more pharmalogical classes such as
inotropic agents, phosphodiesterase inhibitors, Beta and calcium
channel blockers, diuretics, afterload reduction agents, cardiac
glycosides and neurohormonal agents may be administered and various
hemodynamic parameters may be measured. Such methods may be
performed at rest or with exercise, with or without alterations in
cardiac electrical stimulation, as with a pacemaker or
biventricular pacing device. Many other embodiments and variations
are contemplated within the scope of the invention.
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