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Description  |
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BACKGROUND OF THE INVENTION
I. Field of the Invention
This invention relates generally to implantable cardiac rhythm management
apparatus, and more particularly to such an apparatus and method that
automatically establishes an optimum A-V delay interval for a DDD
pacemaker.
II. Discussion of the Prior Art
With present day state-of-the-art, programmable, implantable pacemakers, a
cardiologist is able to periodically program into the device an A-V delay
value that yields an optimum stroke volume by, for example, using external
instrumentation like a Doppler flow meter to measure changes in cardiac
output as the A-V delay interval for the pacer is systematically changed.
Such an approach at optimization is not only time consuming, but may only
be appropriate for the patient at the time that the testing and setting of
the A-V delay interval is made. In the literature, the optimum value of
the A-V delay has generally been defined as that delay value that produces
the maximum stroke volume for a fixed heart rate or the maximum cardiac
output for a sinus node driven heart rate. For patients suffering from
congestive heart failure (CHF), the A-V delay interval can be varied over
a wide range without any measurable change in stroke volume. Studies which
we have conducted suggest that CHF patients would have a very narrow range
for the optimum A-V delay, meaning that small deviations, e.g., only 10
milliseconds, from the optimum can diminish the clinical benefit obtained
using DDD pacing.
To explain these apparently contradictory results, one needs to understand
that the body regulates the heart directly, such as by changing the heart
rate and contractility, through the sympathetic and parasympathetic tones
and indirectly through the load. A major role in this regulatory scheme is
played by the baroreceptors. The baroreceptors, located in the major
thoracic arteries, are pressoreceptors that compare the arterial pressure
with a reference value. If the pressure exceeds the reference value, the
baroreceptors emit signals that enter the tractus solitarius of the
medulla. Secondary signals also inhibit the vasoconstrictor center of the
medulla and excite the vagal center. The net effects are vasodilation of
the veins and the arterioles throughout the peripheral circulatory system
and decreased heart rate and strength of heart contractions. Therefore,
excitation of the baroreceptors by pressure in the arteries reflexly
causes the arterial pressure to decrease because of both a decrease in
peripheral resistance and a decrease in cardiac output. Conversely, low
pressure (a pressure lower than the reference value) has opposite effects,
reflexly causing the pressure to rise back toward normal.
When it is recognized that A-V delay only effects the timing of the atrial
contraction in relationship with the next following ventricular
contraction, a change in A-V delay will only change the hemodynamic
performance of the heart as a mechanical pump. If a patient is not already
using his/her compensation mechanisms, a less than optimal A-V delay would
mechanically impair the pump performance. If this impairment is of a
sufficient degree to produce a pressure change, the baroreceptor mechanism
can come into play to increase the contractility and cancel the
hemodynamic effect that the less than optimum A-V delay would have
produced. The more seriously that the heart of a CHF patient is impaired,
the more his/her organism will use these compensation mechanisms and the
less his/her regulatory system will be able to compensate for a less than
optimum A-V delay. This tends to explain the finding of very narrow ranges
of optimum A-V delays in sick patients.
In 1981, M. Heilman and M. Mirowski proposed a method and apparatus for
maximizing stroke volume through atrioventricular pacing using an
implanted cardioverter/pacer which accomplishes A-V sequential pacing with
an A-V delay tailored to the particular patient. One of its disadvantages
is that it attempted to control the A-V delay on a beat-by-beat basis,
measuring the beat-by-beat stroke volume. However, the beat-by-beat
variation of the peak-to-peak impedance proved not to be a reliable enough
approach to be used as a parameter to determine the A-V delay, since its
amplitude is going to be affected by motion artifacts, electric noise,
etc. Another disadvantage of that method and apparatus is that it does not
provide any way to identify the origin of the stroke volume change, which
could have been produced by a change in heart rate, by a change in the
systemic or peripheral resistance or by a change in the venous return.
Also, any affect of the A-V delay on the stroke volume tends to be masked
by physiologic feedback mechanisms that try to maintain cardiac output
constant so as to satisfy metabolic needs.
We hypothesize that the clinical findings, obtained while using stroke
volume as the variable to optimize A-V delay, have been affected by the
feedback mechanisms that the body normally applies to maintain the supply
of blood during load changes. If this hypothesis is correct, the A-V delay
changes operate to modify the pump performance, but its actual output has
been kept constant by the feedback introduced by the sympathetic and
parasympathetic systems. In patients with a very narrow range for the
optimum A-V delay, it is possible that their feedback mechanisms were
either impaired or already used and, therefore, unable to completely
compensate for the effect produced in the pump efficiency by the A-V
delay.
SUMMARY OF THE INVENTION
The method and apparatus to continuously optimize the A-V delay in
accordance with the present invention is based upon the fact that for
optimum A-V delay, the ratio between the activity of the sympathetic
system and the activity of the parasympathetic system should be a minimum.
This ratio is referred to as the heart rate variability index (HRV.sub.i).
The system of the present invention comprises a conventional implantable
DDD or DDDR cardiac rhythm management device having a telemetry
capability, plus added software or firmware to perform an analysis of the
heart rate variability. In particular, the system comprises a means for
sensing both atrial and ventricular depolarization signals and a means for
stimulating ventricular tissue all under the control of a
microprocessor-based controller that is programmed to determine a
HRV.sub.i during a predetermined time interval. The microprocessor-based
controller responds to the detection of an atrial depolarization signal
and establishes an optimum A-V delay interval corresponding to a minimum
HRV.sub.i. The controller then causes this optimum A-V delay to be used in
timing the occurrence of a ventricular stimulating pulse following the
sensing of an immediately preceding atrial depolarization signal.
To compute the HRV.sub.i, cyclic variations in the R-R interval are
determined during a defined interval and then a frequency domain (power
spectrum) analysis is performed. The power spectrum analysis decomposes
the heart rate signal into its frequency components and quantifies them in
terms of their relative intensity, i e., "power". It is found that the
power spectrum includes a low frequency band and a high frequency band.
HRV.sub.i is the ratio of low frequency power to high frequency power.
It is accordingly a principal object of the present invention to provide in
a single system the ability for automatically programming an optimum A-V
delay interval and a pacing mode for a DDD pacemaker with respect to a
minimum ratio between sympathetic and parasympathetic tones.
Another object of the invention is to provide an apparatus and method for
automatically programming an optimum A-V delay interval and pacing mode
for a patient that does not require external equipment, such as a Doppler
flow meter, since the hardware and software embedded in the implantable
cardiac rhythm management device is itself sufficient to achieve the
optimization.
Yet another object of the invention is to provide a cardiac rhythm
management device for use by patients suffering from CHF that has the
capability of maintaining an optimum A-V delay even when the mode of
pacing is changed.
DESCRIPTION OF THE DRAWINGS
The foregoing features, objects and advantages of the invention will become
apparent to those skilled in the art from the following detailed
description of a preferred embodiment, especially when considered in
conjunction with the accompanying drawings in which:
FIG. 1 illustrates an implantable cardiac rhythm management device coupled
to a patient's heart via appropriate sensing/pacing leads;
FIG. 2 is a general block diagram of the circuitry incorporated in the
cardiac rhythm management device of FIG. 1;
FIG. 3 is a more detailed block diagram of the implementation of the
microprocessor-based controller shown in FIG. 2; and
FIG. 4 is a flow diagram of the software executed by the
microprocessor-based controller shown in FIG. 2 for automatically
maintaining the A-V delay at an optimum value for the particular patient
in whom the system is implanted and used.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring first to FIG. 1, there is indicated generally by numeral 10 a
cardiac rhythm management device, here shown as a DDD bradycardia
pacemaker 12, which is operatively coupled to a patient's heart 14 by
means of a conventional pacing lead 16 having atrial pacing and sensing
electrodes 18 and 20 and ventricular pacing and sensing electrodes 22 and
24.
Referring now to FIG. 2, the atrial sensing electrode 20 disposed in the
right atrium of the heart 14 is coupled by a wire in the lead 16 to an
atrial sense amplifier 26 and, similarly, the ventricular sensing
electrode 24 is connected by a wire in the lead 16 to a ventricular sense
amplifier 28 contained within the pacemaker 12. Thus, when the SA node in
the right atrium depolarizes, the resulting signal is picked up by the
atrial sense amplifier 26 and applied to the microprocessor-based
controller 30. Ventricular depolarization signal (R-Waves) are likewise
amplified and applied as an input to the microprocessor-based controller
30.
As will be more fully explained, the algorithm employed is operative at a
time that the patient is at rest or asleep and to establish that fact,
motion indicative of activity is sensed by an accelerometer 33 and that
information, coupled with heart rate, is used to establish the "at rest"
state.
The microprocessor-based controller is connected in controlling
relationship to a pulse generator 32 to cause a ventricular stimulating
pulse to be applied, via lead 16 and the tip electrode 22, to tissue
located proximate the apex of the right ventricle to initiate ventricular
depolarization that spreads as a wave across both the right and left
ventricles. The microprocessor-based controller 30 not only controls the
rate at which cardiac stimulating pulses are produced, but also the timing
thereof relative to a preceding atrial depolarization signal to thereby
define the A-V interval. An external programmer 34 is arranged to send
radio frequency signals transcutaneously to the implanted pacemaker and
also to receive signals originating in the pacemaker. In this fashion, a
physician is capable of programming such parameters as rate, pulse width,
pulse amplitude, sensitivity, etc., in a fashion known in the art. The
external programmer may also be used to receive signals and to pass them
on to an external monitor (not shown).
Referring next to FIG. 3, there is shown a more detailed block diagram of
the microprocessor-based controller 30. It is seen to include a
microprocessor chip 36 and associated RAM and ROM memory modules 38 and 40
connected to the microprocessor by an address bus and a data bus.
Generally speaking, and without limitation, the RAM memory 38 is capable
of storing data words/operands used in the execution of one or more
programs that may be stored in the ROM memory 40. An input/output
interface module 42 is used to couple a transceiver 44 to the
microprocessor 36 whereby information can be exchanged between the
microprocessor 36 and an external programmer 34, as previously described.
An analog-to-digital (A/D) converter 46 receives inputs from the sense
amplifiers 26 and 28 of FIG. 2 and is effective to digitize the analog
voltage signals for further processing by the microprocessor 36.
The microprocessor 36 provides a control output on line 31 to the pulse
generator 32.
As will be explained in greater detail below, the microprocessor 36 is also
coupled to a Fast Fourier Transform chip 48 which is used in forming the
heart rate variability index, HRV.sub.i. In a paper entitled "Heart Rate
Variability--Frequency Domain Analysis" by Zsolt Ori et al. appearing in
Cardiology Clinics, vol. 10, No. 3, August 1992, there are described, in
detail methods of computing the heart rate a variability by determining
the power in a low frequency portion of the power spectrum and dividing it
by the high frequency power in that same power spectrum. This ratio
corresponds to the ratio of sympathetic tone to parasympathetic tone. An
Appendix to the Ori et al. paper provides the mathematical formula for
estimating the energy distribution over frequency using the classical
power spectrum analysis employing the Fast Fourier Transform (FFT).
Further information on measuring heart rate variability is contained in a
paper by Kleiger et al. entitled "Stability Over Time of Variables
Measuring Heart Rate Variability in Normal Subjects", Am J Cardiol,
68:626-630, 1991. The FFT chip 48 is especially adapted to providing
frequency domain analysis and when applied to the cyclic changes in the
sinus rate over time, HRV.sub.i is computed. A paper entitled "Heart Rate
Variability as a Prognostic Tool in Cardiology" by Maximilian Moser et
al., Circulation, Vol. 90, No. 2, August 1994, describes a method in which
respiratory sinus arrhythmia (RSA) is used to measure parasympathetic tone
and because the standard deviation (SD) of R-R intervals over a
predetermined period of time is a measure of sympathetic and
parasympathetic tone, the heart rate variability index (HRV.sub.i) can be
estimated as:
HRV.sub.i =SD/RSA.
Referring next to FIG. 4, there is shown a software flow diagram of the
algorithm embodied in the microprocessor-based controller 30 for
optimizing the A-V interval of a pacemaker based upon derived minimum
values of HRV.sub.i. The program starts with a first test to determine
whether the patient is in a resting state at block 50. Information from
the accelerometer 33 contained within the implantable pacemaker 12 is
processed to assess the level of physical activity of the patient.
If the patient has been active within a predetermined period of time,
control loops back, via path 52, until a determination is made that he/she
is asleep and control exits on path 54 where a determination is made at
block 56 whether the patient suffers from second or third degree A-V
block. If neither type of heart block is present, the programmable
controller sets the A-V interval to a value that is greater than the
intrinsic PR interval of the heart (block 58) to allow for intrinsic
conduction. Next, variations in the R-R interval of the heart are analyzed
for a predetermined period, such as five minutes (block 60) and the heart
rate variability ratio HRV.sub.i is computed by determining from the FFT
derived power spectrum the low frequency power and high frequency power
components. The ratio thereof is then formed as is more further explained
in the aforereferenced Ori et al. paper. Had it been determined at block
56 that the patient was suffering from second or third degree heart block,
the A-V interval for the pacer would be set to a predetermined initial
value A-V.sub.i at block 62 before the heart rate variability index was
determined at block 60.
Next, the A-V interval of the pacer is set to the initial value A-V.sub.i
plus a time increment equal to a count index, n, times a predetermined
time increment T. The effect of incrementing the A-V interval from its
initial value to the changed value on heart rate variability is again
analyzed over a programmable interval, e.g., five minutes, followed by the
incrementation of the count index at block 68. Each time a heart rate
variability index is computed, it is associated with the particular A-V
interval value existing at the time that the HRV.sub.i value in question
had been determined. Both of these values are temporarily stored in the
RAM memory 38 (FIG. 3).
A test is made at block 70 to determine whether the A-V interval has been
incremented to the point where it exceeds a predetermined limiting value,
e.g., 300 milliseconds. If not, control returns via path 72 to block 56
followed by the iterative execution of the operations defined by blocks
58-68 until the test at block 70 reveals that the incremented value of the
A-V interval reaches 300 milliseconds. At that point, the memory is
searched for the A-V interval value associated with the minimum HRV.sub.i
value and that A-V delay value is then determined to be optimum and used
in controlling the pulse generator 32.
At the same time, the iteration count value, n, is set to zero. Also, a
quality HRV.sub.p referring to the immediately preceding computed heart
rate variability index is set to its maximum. See operation block 72.
Periodically, it is desirable to repeat the "at rest" optimization sequence
just discussed so the algorithm includes the ability to program in a time
value measured in units of days, weeks or months, and then that time value
is decremented by regularly occurring clock signals from the
microprocessor. When the time value is decremented to zero, the "YES"
output of block 74 is followed and the previously described A-V interval
optimization sequence is again executed.
Assuming that it is not time to repeat the "at-rest" sequence, control out
of block 74 follows path 76 and a cycle timer has its contents set to zero
as represented by block 78. Next, the A-V interval of the pulse generator
is set to the previously determined optimum value established at block 72
plus an increment, nT, at block 80. A test is made at block 82 to
determine whether the time value has reached 24 hours and, if not, the
time value is incremented at block 84 on repetitive passes until the test
at block 82 indicates that a 24-hour interval has expired. When it has,
the HRV ratio, determined over the preceding 24-hour period, is calculated
in the fashion already described (block 86). That is to say, data is
gathered over a 24-hour period relating to cyclic variations in the
heart's R-R interval and a frequency domain analysis involving the FFT
signal processing is carried out to locate the low frequency and high
frequency peaks in the power spectrum. The energy associated with the low
frequency peaks is then divided by that associated with the high frequency
peaks in arriving at the HRV ratio.
Next, a test is made at block 88 to determine whether the calculated HRV
ratio exceeds the previous HRV ratio that had been established at block
72. If it does not, a test is made at block 90 to determine whether a flag
bit, F, is set to "decrement". On the first pass through the loop, the
answer will be "no" and the value of n of incremented at block 92 and the
flag bit, F, is toggled to "increment". Next, the previous heart rate
variability index (HRV.sub.p) is set equal to the value computed at block
86. See block 94.
The operation performed at block 96 insures that the index value, n, is
limited to lie between programmable limits, e.g., .+-.5. Control then
returns via path 98 to block 74.
This sequence is repeated at 24 hour intervals later and a new HRV ratio
value is computed each time at block 86 and tested at block 88 to see if
the newly computed value is greater than the previous HRV value. Assuming
it is not, the result of the test at block 90 on the second pass will
again be "NO" because the flag bit, F, had been set to "increment" on the
previous pass. The count value, n, will again be incremented and the
previous HRV value will be replaced by the just calculated value at block
94. The value of "n" is again tested at block 96 to see if it is within
limits. When "n" exceeds its limit (i.e., 5) in the positive direction, on
the next pass, "n" at block 11, will be set to its limit rather than any
value greater than it.
Let it be assumed that on the next pass, the HRV value calculated at block
86, based upon the new value of the A-V delay entered at block 80, exceeds
the previous HRV value. A test at block 100 will result in a "NO" response
since on the previous pass, the flag bit, F, was set to "increment" at
block 92. As a result, n, will be decremented (block 102) and Flag bit is
set to "decrement". Then, the previous value of heart rate variability
index, HRV.sub.p, is replaced with the newly calculated value. If the new
value of n is between the limits (i.e., .+-.5), that value of n will be
used on the next pass.
Next assume that operation continues and a point is reached where the
change in the A-V delay interval causes the calculated HRV.sub.i to exceed
its previous value and the F bit is set to "decrement". Under these
circumstances, control passes to block 104 and the value of n is
incremented by one while the Flag bit, F, is set to "increment" prior to
HRV.sub.p being set equal to the value calculated at block 86.
It can be seen from the above explanation that at 24-hour intervals, a new
A-V delay value (AV.sub.opt +nT) is used by the pacer and HRV ratio, based
on that change,is calculated. If the new value exceeds the previous value,
the counter index, n, is decremented so that on the next pass the quantity
(AV.sub.opt +nT) will be decreased. If on this next pass, the same result
occurs, i.e., HRV is greater than HRV.sub.p, another decrementation cycle
occurs. If a point is reached where further decrementation of the A-V
value results in worsened (larger) HRV ratio than on a preceding cycle,
then n will again be incremented. Thus, the A-V interval value will
oscillate back and forth about an optimum value that yields a minimum HRV
ratio.
In another embodiment, the 25-hour optimization period can be an integer
number of days, weeks, or even months. In still another embodiment, a
measurement of HRV.sub.i during sinus rhythm between two consecutive AV
delays or mode changes can be used to obtain a reference HRV.sub.i. In
this case, the optimum setting would be the one that provides the maximum
decrease in HRV.sub.i with respect to the HRV.sub.i obtained during
intrinsic sinus rhythm. In case of second or third degree AV block, a
standard AV delay and pacing mode can be used for this reference.
A DDD pacemaker having a microprocessor-based controller programmed in
accordance with the flow diagram of FIG. 4 allows the optimum A-V delay of
the pulse generator to be automatically set without the need for
intervention of any external equipment. Furthermore, the approach
described can be extended to optimize the pacing mode of such a cardiac
rhythm management device. In a DDD or a DDDR pacing system, there are four
possible modes of pacing:
(a) sensing in the atrium and sensing in the ventricle;
(b) sensing in the atrium and pacing in the ventricle;
(c) pacing in the atrium and sensing in the ventricle;
and
(d) pacing in the atrium and pacing in the ventricle.
One of the problems faced by a cardiologist in trying to set the A-V delay
of the pacemaker is that the optimum delay is dependent on the current
pacing mode. This is due to the fact that it takes a different time for an
electrical stimulus to propagate from the right atrium to the left atrium,
depending on whether it is a paced beat or a normally generated (sinus
node) beat. At the same time, it will take a greater time for an
electrical stimulus to propagate from the right ventricle (paced
ventricle) to the left ventricle if it is a paced apical stimulus than if
it a normal conducted beat (using the specialized conduction system
composed by the His bundle and purkinje fibers). The method of the present
invention addresses the problem of finding the optimum A-V delay for all
of the above pacing modes for a particular patient, by providing the means
to compensate for the difference in inter-atrial propagation times that
exists between pacing modes (b) and (d) above, by programming the optimum
A-V delay with an A-V delay offset. Those skilled in the art will
appreciate that the present invention is capable of repeating the
above-described procedure for atrial paced beats as well as intrinsic SA
node activity and can program into the device the optimum offset between
atrial paced and sensed beats. The A-V delay scanning window (0-300 ms) is
also programmable and can be divided into time intervals of programmable
length, e.g., five milliseconds.
This invention has been described herein in considerable detail in order to
comply with the Patent Statutes and to provide those skilled in the art
with the information needed to apply the novel principles and to construct
and use such specialized components as are required. However, it is to be
understood that the invention can be carried out by specifically different
equipment and devices, and that various modifications, both as to the
equipment details and operating procedures, can be accomplished without
departing from the scope of the invention itself.
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