Cardiac pacemaker adaptive to physiological requirements

A cardiac pacemaker has a pacing pulse generator whose rate is adjusted as a function of the cardiac output requirements of the body that are commensurate with the activity of the individual. The length of the ventricular preejection period (PEP) is governed by body hormones as well as direct nerve action upon the heart in relation to stress. The PEP is determined by marking occurrence of the onset of a natural ECG signal or artificial pacing pulse, whichever is first to occur in a heart cycle, and detecting left or right ventricular ejection by a pressure or flow pulse in the arterial system or a volume change in the right ventricle. The length of time between the onset of a natural or artificial stimulus and onset of ventricular ejection is the PEP. An electric signal that depends on the PEP is used to regulate the pulse generator rate and escape mechanisms in any of the conventional pacing modes including the AAI, VVI, DVI, VDD and DDD modes.

BACKGROUND OF THE INVENTION 
The invention disclosed herein is a cardiac pacemaker that responds to 
varying physiological or metabolic requirements of the body by 
automatically adjusting the stimulus or pacing rate and, hence, the blood 
pumping rate of an abnormal heart to the same extent that the body would 
naturally adjust the rate of a normal heart for equivalent physiological 
requirements. 
The body maintains a hormone level in the blood that is related to the 
prevailing amount of physical activity and emotional stress. When a person 
increases physical activity voluntarily or is subjected to a challenge 
that results in stress, the level of the activating hormones increases. By 
a complex but short duration chain of events, the heart responds to the 
hormone level or direct nerve action by beating at a higher rate so as to 
pump a sufficient volume of blood for coping with the increased demand. 
The converse of the foregoing occurs when the person goes from a 
physically active state to a resting state. 
Normally, changes in physical activity alter the rate of the nerve impulses 
to the sino-atrial (SA) node of the heart. This node depolarizes in 
response to receiving said nerve impulses and causes an electric signal to 
be propagated over the atrium which causes it to contract and discharge 
blood into the ventricles. The atrial signal is conducted to the 
atrio-ventricular (AV) node which, after a short delay, causes a 
depolarizing signal to be propagated over the ventricles, thus causing the 
ventricles to contract and to discharge blood to the aorta and pulmonary 
artery. Simultaneously with increased rate, ventricular contractility is 
enhanced. 
The electrical system of the heart is subject to various kinds of failures. 
In some cases, the natural or intrinsic electric signals of the atrium 
occur at a rate in correspondence with hormone levels and physiological 
requirements but the signals are not propagated to or through the Purkinje 
fibers which conduct the signals from the AV node to the ventricles. 
Hence, the ventricles do not depolarize immediately in which case 
ventricular contraction is delayed and falls out of synchronism with the 
atrium. The ventricles have an escape capability which is to say that even 
though they do not receive a conducted signal they will depolarize by 
themselves eventually and cause ventricular contraction. This slow 
ventricular rate results in an inadequate supply of blood to the organs 
which reduces patient's work capacity and can result in a patient 
fainting, especially if an attempt is made to increase activity. 
In some individuals, the defect in the electrical system of the heart is 
such that the heart generates natural or intrinsic stimulus signals some 
of the time but fails to generate them at other times. Pacemakers that 
provide artificial electric stimuli on demand are usually implanted in the 
subject when ventricular contractions are missed or unduly delayed 
periodically. The latest demand pacemaker designs can be programmed from 
outside of the body to operate in any of several modes. For instance, a 
pacemaker may be controlled to pace the atrium only, or to pace ventricles 
only, or to pace the heart chambers synchronously, first the atrium, then 
delay, then ventricle stimulation. In demand pacemakers, the pacing rate 
is set sufficiently high to assure that enough blood will be pumped to 
permit a limited amount of physical activity above a resting state. 
In some cases the pacemaker is operated in the atrial synchronous mode. The 
atrial signal is detected and used to adjust the artificial stimulus or 
pacing rate of the pacing pulse generator in the ventricle to match 
physiological requirements. This is based on the assumption that the nerve 
impulses to the SA node increase and decrease faithfully in response to 
changes in demand. There is coordination between the natural atrial signal 
timing and variable physiological requirements, but the signals are 
difficult to detect with accuracy. In some subjects, the atrial signal is 
not synchronized with the ventricular signal. U.S. Pat. No. 4,313,442 
exhibits one attempt to solve this problem. 
It is known that with a healthy heart, the QT interval in the natural ECG 
signal changes in relation to physiological demand, that is, the QT 
interval shortens as exercise is increased. U.S Pat. No. 4,228,803 uses 
this phenomenon to adjust the artificial stimulus pulse rate in relation 
to physiological requirements. The interval between the QRS complex in the 
ECG waveform and the T-wave is measured for every heart beat. As the 
T-wave interval shortens, the rate of the stimulus pulse generator is 
increased and as the interval lengthens, the pulse rate is decreased. This 
has not completely solved the problem of coordinating pacing rate with 
physiological demand because the QT interval is not wholly independent of 
pacing rate. When physical activity of the person is increased 
voluntarily, a natural contribution to shortening the T-wave interval 
occurs. The pacemaker senses this as a requirement for increasing the 
artificial stimulus rate. This shortens the interval further. Thus, there 
is a positive feedback and the pacemaker can go into a needless cycle of 
self-acceleration. Pacemakers of this type can increase the stimulus pulse 
rate even though physical activity has not increased. 
Other attempts have been made to match stimulus pulse rate with 
physiological needs. One example is given in U.S. Pat. No. 4,009,721 which 
is based on recognition that the pH level of the blood is a function of 
physical activity. The pH is detected and converted to a signal useful for 
adjusting the rate of the stimulus pulse generator. However, there is 
doubt as to whether a system can respond to physiological requirements on 
a beat-to-beat basis. 
A deficiency that exists in all prior art pacemakers which attempt to 
respond to physiological requirements is that they do not change stimulus 
rate in response to emotional stress or simply a challenge to the body 
without increase in physical activity as nature provides in a healthy 
individual with a normal heart. 
SUMMARY OF THE INVENTION 
In accordance with the present invention, regulation of the stimulus pulse 
rate of an electronic pacemaker is based upon the recognition that in 
subjects which have either normal or abnormal cardiac electrical systems, 
the ventricular preejection period (PEP) and the isovolumic contraction 
time (IVCT) within said period vary naturally and faithfully in direct 
correspondence with physiological requirements of the body. 
As is well known, during systole, that is, during ventricular contraction, 
blood pressure in the aorta and pulmonary artery rises until their valves 
close after which the pressure pulse declines to a rather steady state 
during diastole. A cardiac cycle begins with initiation of the QRS complex 
in the electrocardiogram (ECG) waveform. It takes a certain amount of 
time-for an intrinsic heart stimulus signal or an artificial pacing pulse 
to propagate and to effect depolarization of the ventricular tissue cells 
so there is a short delay before ventricular contraction starts. The point 
in time at which contract,ion starts coincides with the beginning of the 
isovolumic contraction time (IVCT). During IVCT there is no ejection of 
blood from the ventricles. Finally, the pressure in the ventricles exceeds 
the residual back pressure in the aorta or pulmonary artery and 
ventricular ejection begins. The time elapsed between the beginning of the 
QRS complex or the artificial pacing pulse and the onset of ventricular 
contraction is defined as the preejection period (PEP). 
When the body is subjected to any physical or emotional stress and when 
physical activity is voluntarily increased, there is an increased 
sympathetic nerve action upon the heart and catecholamines release by the 
adrenal glands into the blood stream. This enhances metabolic activity in 
the musculature sufficiently to effect the necessary response to the 
stress or increased activity by increasing contractility of the heart and 
its rate. It has been demonstrated that the IVCT varies with the 
cathecolamine levels and decreases in length as physical activity 
increases and increases as physical activity is decreased. A study and 
confirmation of this phenomenon is presented in Harris, W. S., Schoenfeld, 
CD, and Weissler, A. M.: "Effects Of Adrenergic Receptor Activation and 
Blockade on the Systolic Preejection Period, Heart Rate, and Atrial 
Pressure in Man". The Journal of Clinical Investigation Vol. 46 No. 11, 
1967. Tests conducted in connection with establishing the hypothesis of 
the present invention confirm the value and consistent relationship of 
IVCT and PEP with changes in stress and activity. 
In accordance with the present invention, an artificial electronic 
pacemaker is adapted to alter its stimulus pulse rate in response to body 
controlled variations in PEP which parallel the normal atrial rate 
variations from the same stimuli. 
The primary objective of the invention is to provide an artificial 
pacemaker device with the capability of altering its stimulus pulse rate 
and, hence, control the blood volume pumped, in faithful conformity with 
metabolic requirements of the body just as a healthy body and heart 
respond to said requirements. 
Another objective is to achieve, for the first time in pacemaker 
technology, alteration of the stimulus pulse rate in response to the body 
simply being subjected to emotional and other non-dynamic challenges such 
as hot, cold, fear or isometric stress analogously to the way a normal 
body functions. 
Another objective is to provide a device for controlling stimulus pulse 
rate that can be incorporated in most, if not all, modern pacemaker 
designs. 
Briefly stated, the new pacemaker system comprises a first device that 
senses the beginning of each natural QRS waveform in the ECG signal. If 
there is no natural QRS signal within an escape interval to cause the 
heart to beat, then the artificial stimulus pulse provided as a substitute 
by the pacemaker is sensed. In either case, the sensed signal corresponds 
to the time the heart is being signalled to initiate ventricular 
contraction. After a delay extending to the beginning of the IVCT, the 
ventricles begin to contract, but no blood is being ejected as yet. A 
second sensor is used to detect the moment the blood pressure in the 
contracting ventricle equals the static diastolic pressure in the aorta or 
pulmonary artery or when blood begins to flow in said vessels or other 
arteries. The time corresponds to the onset of ventricular ejection and 
constitutes the end of the PEP. Thus, with the beginning of the QRS 
complex or signal being sensed and the subsequent signal indicative of 
ventricular ejection being sensed, the time of ejection relative to the 
beginning of the QRS signal can be measured and the measured interval 
represents the PEP. A signal corresponding to the variable PEP and, hence, 
to variable physiological requirements is used to adjust the pacemaker 
stimulus pulse rate and escape interval. 
As previously indicated, it is the IVCT that is caused to vary naturally in 
response to the cathecolamines that are released into the blood as well as 
to direct sympathetic nerve activity when physiological requirements 
increase. Measurements show, however, that the delay between onset of the 
QRS complex and the onset of IVCT is constant for each patient and the 
delay between an artificial stimulus pulse and onset of the IVCT is also 
constant for each patient. It is difficult to sense the onset of the IVCT 
on a continuing basis outside of the laboratory, that is, in a mobile 
patient. However, if the PEP is measured as is the case here, it will vary 
faithfully in proportion to physiological requirements and will be wholly 
independent of the largely uncertain changes in the QT interval as 
activity changes. 
That there is direct correlation between IVCT, PEP and ventricular ejection 
is shown by Martin, C. E., Shaver, J. A., Thompson, M. E., Reddy, P. S. 
and Leonard, J. J.: "Direct Correlation of External Systolic Time 
Intervals With Internal Indices of Left Ventricular Function In Man." 
Circulation, Vol. XLIV, September 1971. That left ventricular ejection 
time (LVET) can be determined by sensing pressure or flow in a variety of 
blood vessels besides the aorta with various types of sensing means is 
demonstrated by Chirife, R., Pigott, V. M., Spodick, D. H.: "Measurement 
of the Left Ventricular Ejection Time By Digital Plethysmography." 
American Heart Journal Vol. 82 no. 2 pp. 222-227, August 1971. Also by the 
same researchers: "Ejection Time By Ear Densitogram and Its Derivative." 
Circulation Vol. XLVIII, August 1973. 
A more detailed explanation of an illustrative embodiment of the invention 
will now be set forth in reference to the drawing.

DESCRIPTION OF A PREFERRED EMBODIMENT 
The simplified block diagram of a pacemaker in FIG. 1 depicts one example 
of how the concept of controlling stimulus rate in response to variations 
in the pre-ejection period (PEP) can be implemented. As usual, the 
pacemaker is connected to the heart by means of a conductive lead 14 which 
terminates in an electrode E that contacts the heart. Lead 14 is used to 
conduct artificial stimulus pulses from the pacemaker to the heart and to 
pick up natural or intrinsic electric signals on the heart and conduct 
them to the pacemaker. It is the onset of the QRS signal that is of 
special interest insofar as the invention is concerned. 
In accordance with the invention, means are provided for regulating the 
stimulus pulse rate in response to variations in the isovolumic 
contraction time (IVCT) determined by measuring the more easily measurable 
PEP which is linearly related to the IVCT. The onset of ventricular 
ejection during each heartbeat is a marker for the end of the PEP. The end 
of the PEP is determined by sensing the abrupt increase in arterial blood 
flow that occurs at the onset of ventricular ejection from either 
ventricle. A blood flow sensor is symbolized in FIG. 1 by an encircled S. 
Several known types of sensors are adaptable to use with body implantable 
pacemakers for the purposes of the invention. As one example, a sensor in 
the form of a photoelectric transducer may be used as described by Chirife 
and Spodick (Amer. Heart J. 83:493, 1972). Sensors that sense, coincident 
with ejection, impedance changes in the right ventricle or impedance 
changes in tissue proximate to arterial vessels anywhere in the body are 
also suitable. A right ventricular volume detector of the type described 
by Salo et al (E 7:1267, 1984) is suitable too. In general, any 
implantable device that produces an electric signal in response to the 
abrupt change in arterial flow or ventricular volume that coincides with 
ventricular ejection may be used. 
The pacemaker in FIG. 1 is a demand type which is characterized by 
providing an artificial stimulus to the heart by way of lead 14 and 
electrode E if the natural or intrinsic QRS signal is missing or unduly 
delayed beyond the escape interval of the pacemaker in any heartbeat 
cycle. Production of a stimulus by stimulus pulse output generator 1 
causes a logic switch 2 to open and remain open during a period determined 
by a refractory period timer 3. This is a conventional feature in demand 
pacemakers and assures that the pacemaker will be insensitive to signals 
such as the evoked QRS or T wave which would adversely affect functioning 
of the circuit. 
In each heartbeat cycle sensor S produces a signal indicative of the onset 
of ventricular ejection and, hence, the end of the PEP. The starting point 
of the PEP coincides with the occurrence of the onset of the intrinsic QRS 
signal or the stimulus pulse whichever occurs first in a heart cycle. The 
signal from sensor S is supplied by way of a lead 15 to an amplifier 6 in 
the implanted unit and through a logic switch 4. The output from amplifier 
6 is conducted to a signal conditioning circuit 7 which uses bandpass 
filters and other components, not shown, to discriminate against 
electrical and motion artifacts in a manner known to pacemaker circuit 
designers. 
The PEP measuring circuit 8 has an input 16 for a signal corresponding to 
the stimulus pulse, if any, and an input 17 for any detected intrinsic QRS 
onset signal and an input 18 for the signal indicative of ventricular 
ejection and the end of the PEP. Thus, the measuring circuit has the 
information it needs for producing a signal whose value represents the 
duration of the PEP. 
The stimulus timing signal generator 10 controls the rate of the stimulus 
pulse output generator 1. Generator 10 may be implemented with analog 
circuitry or digital logic circuitry. Basically, generator 10 generates a 
signal whose value increases in respect to time and which is reset to a 
predetermined value such as 0 concurrently with occurrence of each natural 
or artificial stimulus signal. In a digital implementation of generator 
10, clock pulses may be counted to determine the elapsed time since the 
last heart stimulus and to set the time for the next one as governed by 
the measured PEP. When physiological demand is low as when the body is at 
rest, the PEP is longest and the timing signal generator 10 triggers the 
stimulus pulse generator 1 at the lowest rate. The escape interval or 
longest time permissible between heartbeats is indicated as having been 
reached when the number of clock pulses counted since reset exceeds a 
programmable predetermined number in which case the timing signal 
generator 10 triggers the stimulus pulse generator 1. 
As physical or emotional activity increases, the PEP becomes increasingly 
shorter and the PEP measuring circuit 8 output signal is translated by a 
timing modifier circuit 9 into a signal that is sent to timing signal 
generator 10 by way of line 19. This signal controls the timing signal 
generator 10 to increase the stimulus pulse rate commensurate with the 
current level of physical activity. The opposite occurs when the PEP 
increases as a result of a decline in physical activity or emotional 
arousal. 
In an analog signal circuit implementation of the pacemaker, generator 10 
is a ramp signal generator and the slope of the ramp is set with a PEP 
signal responsive modifier 9 that changes the slope of the ramp as a 
function of the PEP measured in circuit 8. Again, the relationship between 
the measured PEP and the slope of the timing ramp generator is externally 
programmable through modifier circuit 9. A modification in the ramp slope 
causes the escape interval of the pacemaker to be changed, which in the 
absence of natural or spontaneous QRS signals will result in a modified 
pacing rate. 
In either the digital or analog circuit implementations of the invention, 
the stimulus timing signal generator 10 sets an escape interval 
appropriate to current physiological demand which corresponds to the 
duration of the measured PEP. 
Every time a natural QRS signal is detected by electrode E outside of the 
refractory period so switch 2 is closed, the signal is amplified by 
amplifier 11 and conditioned by conditioner 12 so it will cause reset 
circuit 13 to reset the stimulus timing signal generator 10 to thereby 
initiate a new cycle. Any detected natural QRS signal or artificial pacing 
stimulus, whichever occurs first, will activate a window circuit 5 after a 
programmable delay. Logic switch 4 closes in response to a window interval 
being started. The use of a programmable delay accounts for the difference 
among individuals in the elapsed time between occurrence of the natural or 
artificial stimulus and the start of ventricular ejection. The stimulus 
signal timing generator 10 will thus be updated by the PEP measurement 
either from the detected spontaneous QRS signal or the pacing stimulus to 
the onset of ejection. 
Attention is now invited to FIG. 2 which shows an ECG waveform 25 and a 
waveform 26 obtained by densitometry measurement concurrently with the 
ECG. A typical PEP is marked off. The PEP begins when the heart is 
stimulated to beat by a pacing pulse. The heart stimulus pacing pulse or 
the intrinsic pacing pulse, whichever is first to occur in a heart cycle, 
is detected to mark the start of the PEP. One typical artificial stimulus 
pulse to which attention is directed is marked 27. In reality, the pace 
pulses coincide with the onset of the evoked QRS signal. In any event, one 
may see that the electric signal is applied to the heart for artificial 
stimulation at a point marked 28 on the pulse waveform 26. There is some 
delay after the pacing pulse 27 occurs before the heart begins to contract 
but the delay is constant in any given patient. For a period after the 
ventricle begins to contract, there is no left ventricular ejection to the 
aorta. This is so because there is a back pressure in the aorta from the 
preceding heart beats which must be exceeded before there is ejection 
under the influence of the contracting left ventricle. The moment of 
ejection by either ventricle marks the end of the PEP. The measured time 
between occurrence of the pace signal and ventricular ejection varies in 
accordance with physical and emotional activity of the body. In other 
words, the PEP shortens as body activity increases and lengthens as body 
activity decreases. This is true whether the patient is being artificially 
stimulated or naturally stimulated for any given heartbeat. It is the 
cathecolamines and the direct sympathetic nerve action upon the heart that 
have the effect of varying the PEP when physiological demand for blood 
increases. In accordance with the present invention, the PEP is measured 
instead of the IVCT and since it depends on a delay time following the 
stimulus pulse plus the IVCT, the IVCT in effect, can be calculated by 
measuring the PEP. This is evident from the waveforms taken from a patient 
depicted in FIG. 2. All one has to do, in accordance with the invention, 
is detect the Q-wave or pacing stimulus at point 28, for instance, and the 
beginning of left ventricular ejection such as at point 29 and a signal 
proportional to IVCT is obtained. Detecting right ventricular ejection 
provides the same result. 
FIG. 3 is a flow diagram defining the operational sequences of a pacemaker 
using the new feature of adjusting rate in response to variations in the 
length of the PEP. Measurement of the length of the PEP as an indicator of 
the IVCT for every heartbeat permits the adjustment of the timing controls 
for the stimulus pulse generator in accordance with the demands of the 
body for blood flow. Starting with a pacing stimulus 31, a measurement 
window begins after a programmable delay 32 which will differ among 
individual patients. During this window, a blood pulse wave or ventricular 
ejection 33 may be detected by the particular previously mentioned sensing 
device that is used to indicate ventricular ejection. If, (yes) a pulse 
wave or ejection is detected, the length of the PEP is measured 34 and the 
timing circuitry 35 of the pacemaker is adjusted; that is, the stimulus 
pulse rate and escape interval duration are adjusted. During this alert 
period, either a normally conducted or ectopic spontaneous QRS (R-wave) 
may occur. If, (no) an R-wave 36 is not detected, a new pacing stimulus 31 
is delivered to the heart prior to the end or at the end of an escape 
interval. If (yes) a QRS or R-wave 36 of said characteristics is present, 
a new delay 37 is created, followed by a blood pulse detection window 38. 
If a pulse is detected and PEP measured 39, similar to the above, the 
timing 40 will again be set, with which the cycle may close with the 
detection of a patient's R-wave 36 or a pacing stimulus 31. If, on the 
other hand, following a pacing stimulus 31, no pulse 33 is detected, the 
stimulus timing will not be modified and the pacemaker will operate in an 
R-wave 42 demand mode at its preset lower rate. Delay 41 constitutes the 
alert period for R-wave sensing. 
With the invention, anything that would bring about an acceleration of a 
normal heart will increase the artificial stimulus pulse rate. It has been 
observed that, besides physical activity, psychological events such as a 
pleasant or an unpleasant surprise caused the PEP to decrease with the 
result that the pace pulse rate is increased. The new device is sensitive 
and can completely restore heart function to normalcy. In healthy 
individuals the carotid sinuses detect pressure in the arteries. Once 
pressure is increased in the carotid sinus there is another mechanism 
which inhibits the heart or slows it down normally by a very small amount 
in a normal person mediated by the vagus nerve or parasympathetic system. 
Particularly in elderly patients who have a diseased, hypersensitive 
carotid sinus and a prevailing high blood pressure or calcification of the 
carotid artery, the carotid sinuses respond to the mechanical stimuli by 
slowing down the heart beat too much in which case the patient can faint. 
The carotid sinuses, of course, provide the signals to the brain and nerve 
circuits to change the heart rate by nerve action on the SA node. 
Fortunately, the new system is insensitive to vagal stimulation because 
the new device does not respond like a normal atrium in this particular 
case. The new pacemaker system controls the rate in correspondence with 
PEP (sympathetic action), so carotid pressure will not affect the pacing 
rate. Said pacing rate would be that existing prior to the time of carotid 
stimulation and would correspond to the demands of the body for blood at 
the prevailing level of activity.