U.S. patent application number 13/569523 was filed with the patent office on 2012-11-29 for secure and efficacious therapy delivery for a pacing engine.
This patent application is currently assigned to Medtronic, Inc.. Invention is credited to Kenneth M. Anderson, John E. Burnes, D. Curtis Deno, Edwin G. Duffin, David E. Euler, Jeffrey M. Gillberg, David A. Igel, Karen J. Kleckner, Ruth N. Klepfer, Lawrence J. Mulligan, Kathleen A. Prieve, Vincent E. Splett, Ren Zhou, Glenn C. Zillmer.
Application Number | 20120303084 13/569523 |
Document ID | / |
Family ID | 34437297 |
Filed Date | 2012-11-29 |
United States Patent
Application |
20120303084 |
Kind Code |
A1 |
Kleckner; Karen J. ; et
al. |
November 29, 2012 |
SECURE AND EFFICACIOUS THERAPY DELIVERY FOR A PACING ENGINE
Abstract
The above-described methods and apparatus are believed to be of
particular benefit for patients suffering heart failure including
cardiac dysfunction, chronic HF, and the like and all variants as
described herein and including those known to those of skill in the
art to which the invention is directed. It will understood that the
present invention offers the possibility of monitoring and therapy
of a wide variety of acute and chronic cardiac dysfunctions. The
current invention provides systems and methods for delivering
therapy for cardiac hemodynamic dysfunction via the innervated
myocardial substrate receives one or more discrete pulses of
electrical stimulation during the refractory period of said
innervated myocardial substrate.
Inventors: |
Kleckner; Karen J.; (New
Brighton, MN) ; Prieve; Kathleen A.; (Shoreview,
MN) ; Gillberg; Jeffrey M.; (Coon Rapids, MN)
; Zhou; Ren; (Blaine, MN) ; Anderson; Kenneth
M.; (Bloomington, MN) ; Deno; D. Curtis;
(Andover, MN) ; Zillmer; Glenn C.; (Hudson,
WI) ; Klepfer; Ruth N.; (St. Louis Park, MN) ;
Splett; Vincent E.; (Apple Valley, MN) ; Euler; David
E.; (Plymouth, MN) ; Mulligan; Lawrence J.;
(Andover, MN) ; Duffin; Edwin G.; (North Oaks,
MN) ; Igel; David A.; (Lino Lakes, MN) ;
Burnes; John E.; (Andover, MN) |
Assignee: |
Medtronic, Inc.
Minneapolis
MN
|
Family ID: |
34437297 |
Appl. No.: |
13/569523 |
Filed: |
August 8, 2012 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
12633893 |
Dec 9, 2009 |
|
|
|
13569523 |
|
|
|
|
11765260 |
Jun 19, 2007 |
|
|
|
12633893 |
|
|
|
|
10703956 |
Nov 7, 2003 |
7233824 |
|
|
11765260 |
|
|
|
|
60509335 |
Oct 7, 2003 |
|
|
|
Current U.S.
Class: |
607/25 |
Current CPC
Class: |
A61N 1/36843 20170801;
A61N 1/36842 20170801; A61N 1/3684 20130101; A61N 1/36521 20130101;
A61N 1/36114 20130101; A61N 1/36585 20130101; A61N 1/36578
20130101; A61N 1/3627 20130101; A61N 1/36564 20130101 |
Class at
Publication: |
607/25 |
International
Class: |
A61N 1/365 20060101
A61N001/365 |
Claims
1. A method of cardiac pacing, comprising: sensing depolarizations
of an atrium and a ventricle of a patient's heart using an
implantable cardiac pacemaker; delivering atrial pacing pulses to
the atrium of the patient's heart using the pacemaker; and at a
selected time Tx following a sensed depolarization of the ventricle
resulting from a preceding conducted atrial depolarization,
delivering an atrial coupled (ACP) atrial pacing pulse; wherein Tx
is selected such that an atrial depolarization resulting from the
delivered ACP atrial pacing pulse is not conducted to the ventricle
because the ventricle is in a refractory state.
2. A method according to claim 1, wherein the preceding conducted
atrial depolarization comprises a sensed atrial depolarization.
3. A method according to claim 2 further comprising delivering a
pacing pulse to the ventricle following the sensed depolarization
of the ventricle and wherein Tx is selected such that an atrial
depolarization resulting from the delivered ACP atrial pacing pulse
is not conducted to the ventricle because the ventricle is in a
refractory state due to the delivered ventricular pacing pulse.
4. . A method according to claim 1, wherein the conducted atrial
depolarization comprises a paced atrial depolarization.
5. A method according to claim 4 further comprising delivering a
pacing pulse to the ventricle following the sensed depolarization
of the ventricle and wherein Tx is selected such that an atrial
depolarization resulting from the delivered ACP atrial pacing pulse
is not conducted to the ventricle because the ventricle is in a
refractory state due to the delivered ventricular pacing pulse.
6. An implantable cardiac pacemaker, comprising : means for sensing
depolarizations of an atrium and a ventricle of a patient's heart;
means for delivering atrial pacing pulses to the atrium of the
patient's heart; and means for, at a selected time Tx following a
sensed depolarization of the ventricle resulting from a preceding
conducted atrial depolarization, delivering an atrial coupled (ACP)
atrial pacing pulse; wherein Tx is selected such that an atrial
depolarization resulting from the delivered ACP atrial pacing pulse
is not conducted to the ventricle because the ventricle is in a
refractory state.
7. A pacemaker according to claim 6, wherein the preceding
conducted atrial depolarization comprises a sensed atrial
depolarization.
8. A pacemaker according to claim 7 further comprising means for
delivering a pacing pulse to the ventricle following the sensed
depolarization of the ventricle and wherein Tx is selected such
that an atrial depolarization resulting from the delivered ACP
atrial pacing pulse is not conducted to the ventricle because the
ventricle is in a refractory state due to the delivered ventricular
pacing pulse.
9. . A pacemaker according to claim 6, wherein the conducted atrial
depolarization comprises a paced atrial depolarization.
10. A pacemaker according to claim 6 further comprising means for
delivering a pacing pulse to the ventricle following the sensed
depolarization of the ventricle and wherein Tx is selected such
that an atrial depolarization resulting from the delivered ACP
atrial pacing pulse is not conducted to the ventricle because the
ventricle is in a refractory state due to the delivered ventricular
pacing pulse.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This patent disclosure is a divisional of Ser. No.
12/633,893, filed Dec. 9, 2009 which is a continuation of Ser. No.
11/765,260, filed Jun. 19, 2007 which is a continuation-in-part of
co-pending non-provisional U.S. patent application Ser/ No.
10/703,956 entitled, "SECURE AND EFFICACIOUS THERAPY DELIVERY FOR
AN EXTRA-SYSTOLIC STIMULATION PACING ENGINE," filed Nov. 7, 2003
and issued 19 Jun. 2007 as U.S. Pat. No. 7,233,824, which also
claims the benefit of U.S. Provisional Application No. 60/509,335,
filed on Oct. 7, 2003. The disclosure of the above application is
incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to implantable
medical devices and more specifically to providing appropriate
therapies for acute or chronic cardiac mechanical dysfunction such
as heart failure (HF), cardiogenic shock, pulseless electrical
activity (PEA), or electromechanical dissociation (EMD).
BACKGROUND OF THE INVENTION
[0003] Patients suffering from chronic HF manifest an elevation of
left ventricular end-diastolic pressure and frequently volume,
according to the well-known heterometric autoregulation principles
espoused by Frank and Starling. This may also occur while left
ventricular end-diastolic volume remains normal due to a decrease
in left ventricular compliance concomitant with increased
ventricular wall stiffness. HF due to chronic hypertension,
ischemia, infarct or idiopathic cardiomyopathy is associated with
compromised systolic and diastolic function involving decreased
atrial and ventricular muscle compliance. These may be conditions
associated with chronic disease processes or complications from
cardiac surgery with or without specific disease processes. Most
heart failure patients do not normally suffer from a defect in the
conduction system leading to ventricular bradycardia, but rather
suffer from symptoms which may include a general weakening of the
contractile function of the cardiac muscle, attendant enlargement
thereof, impaired myocardial relaxation and depressed ventricular
filling characteristics in the diastolic phase following
contraction. Pulmonary edema, shortness of breath, and disruption
in systemic blood pressure are associated with acute exacerbations
of heart failure. All these disease processes lead to insufficient
cardiac output to sustain mild or moderate levels of exercise and
proper function of other body organs, and progressive worsening
eventually results in cardiogenic shock, arrhythmias,
electromechanical dissociation, and death.
[0004] Such patients are normally treated with drug therapies,
including digitalis, which may lead to toxicity or lose
effectiveness over time. Many inotropic drugs have recently become
available, targeted at various receptors in the myocyte and
designed for the purpose of directly stimulating cardiac tissue in
order to increase contractility. However, there exist many possible
undesirable side effects, in addition to the fact that these drugs
do not always work for their intended purpose. This is especially
characteristic of the patient suffering from end-stage heart
failure.
[0005] Since dual chamber pacing was developed, conventional,
atrioventricular (AV) synchronous pacing systems, including DDD and
DDDR pacing systems, marketed by Medtronic, Inc. and other
companies, have also been prescribed for treatment of HF as well as
a variety of bradycardia conditions. Certain patient groups
suffering heart failure symptoms with or without bradycardia tend
to do much better hemodynamically with AV synchronous pacing due to
the added contribution of atrial contraction to ventricular filling
and subsequent contraction. However, fixed or physiologic sensor
driven rate responsive pacing in such patients does not always lead
to improvement in cardiac output and alleviation of the symptoms
attendant to such disease processes because it is difficult to
assess the degree of compromise of cardiac output caused by HF and
to determine the pacing parameters that are optimal for maximizing
cardiac output. Selection of an optimal AV delay often requires
obtaining pressure data involving an extensive patient work-up as
set forth in commonly assigned U.S. Pat. No. 5,626,623.
[0006] A series of PCT publications including, for example, PCT WO
97/25098 describe the application of one or more "non-excitatory"
anodal or cathodal stimulation pulses to the heart and maintain
that improvements in LV performance may be realized without
capturing the heart. In a further commonly assigned U.S. Pat. No.
5,800,464, the contents of which are hereby incorporated by
reference herein, sub-threshold anodal stimulation is provided to
the heart to condition the heart to mechanically respond more
vigorously to the conventional cathodal supra-threshold pacing
pulses.
[0007] Thus, various stimulation regimens have been proposed for
the treatment of cardiac dysfunction including HF which involve
application of supra-threshold and/or sub-threshold stimulation
paired or coupled pacing pulses or pulse trains. Moreover, various
electrodes have been proposed for single site and multi-site
delivery of the stimulation pulses to one or more heart chambers in
the above-referenced patents and publications. However, it remains
difficult to economically determine appropriate candidates that
would benefit from such stimulation and to measure the efficacy of
a given stimulation regimen and/or electrode array. Extensive
catheterization procedures must be conducted of a heart failure
patient to determine if he or she is a candidate for implantation
of such a system. Then, the efficacy of any given treatment must be
assessed at implantation and in periodic post-implant follow-up
clinical tests. The patient work-up and follow-up testing must take
into account or simulate known patient activities, patient posture,
and whether the patient is awake or asleep in order to be
representative of the heart failure condition over a daily time
span. Furthermore, these therapies are susceptible to losing
efficacy or causing arrhythmias with shifts in stimulation timing
or the physiologic response to stimulation.
[0008] Physiologic and device operating data gathering capabilities
have been included in modern implantable cardiac pacemakers and
implantable cardioverter/defibrillators (ICDs) in order to provide
a record of bradycardia or tachyarrhythmia episodes and the
response to same provided by the pacemaker or ICD. The stored
physiologic device operations and patient data as well as real-time
electrogram (EGM) data can be uplink telemetered to an external
programmer for display and analysis by medical heath care
providers, as is well known in the art. In addition, implantable
cardiac monitors have been clinically used or proposed for use for
monitoring hemodynamic and electrical signals of a patient's heart
that do not presently include any stimulation capabilities, e.g.,
cardiac pacing or cardioversion/defibrillation. Such implantable
monitors are implanted in patients to develop data over a longer
time period than in the clinical setting that can be retrieved in
the same manner and used to diagnose a cardiac dysfunction,
including
[0009] HF, that manifests itself sporadically or under certain
loads and stresses of daily living.
[0010] One such implantable EGM monitor for recording the cardiac
electrogram from electrodes remote from the heart as disclosed in
commonly assigned U.S. Pat. No. 5,331,966 and PCT publication WO
98/02209 is embodied in the Medtronic.RTM. REVEAL.RTM. Insertable
Loop Recorder having spaced housing EGM electrodes. More elaborate
implantable hemodynamic monitors (IHMs) for recording the EGM from
electrodes placed in or about the heart and other physiologic
sensor derived signals, e.g., one or more of blood pressure, blood
gases, temperature, electrical impedance of the heart and/or chest,
and patient activity have also been proposed. The Medtronic.RTM.
CHRONICLE.RTM. IHM is an example of such a monitor that is coupled
through a lead of the type described in commonly assigned U.S. Pat.
No. 5,564,434 having capacitive blood pressure and temperature
sensors as well as EGM sense electrodes. Such implantable monitors
when implanted in patients suffering from cardiac arrhythmias or
heart failure accumulate date and time stamped data that can be of
use in determining the condition of the heart over an extended
period of time and while the patient is engaged in daily
activities.
[0011] A HF monitor/stimulator is disclosed in commonly assigned
U.S. Pat. No. 6,104,949 that senses the trans-thoracic impedance as
well as patient posture and provides a record of same to diagnose
and assess the degree and progression of HF. The sensed
trans-thoracic impedance is dependent on the blood or fluid content
of the lungs and assists in the detection and quantification of
pulmonary edema symptomatic of HF. Trans-thoracic impedance is
affected by posture, i.e. whether the subject is lying down or
standing up, and the sensed trans-thoracic impedance is correlated
to the output of the patient posture detector to make a
determination of presence of and the degree of pulmonary edema for
therapy delivery and/or physiologic data storage decisions.
[0012] A monitor/stimulator is disclosed in U.S. Pat. No.
5,417,717, that monitors and assesses the level of cardiac function
then permits a physician to arbitrate the therapy mode, if therapy
is indicated. The monitor/stimulator assesses impedance, EGM,
and/or pressure measurements, and then calculates various cardiac
parameters. The results of these calculations determine the mode of
therapy to be chosen. Therapy may be administered by the device
itself or a control signal may be telemetered to various peripheral
devices aimed at enhancing the heart's function. Alternatively, the
device may be programmed to monitor and either store or telemeter
information without delivering therapy.
[0013] Particularly, the implantable monitor/stimulator monitors
conventional parameters of cardiac function and contractile state,
including all phases of the cardiac cycle. Thus, assessments of
contractile state measured include indices of both cardiac
relaxation and contraction. Utilizing the dual source ventricular
impedance plethysmography technique described in U.S. Pat. No.
4,674,518, the monitor/stimulator monitors cardiac function by
assessing hemodynamic changes in ventricular filling and ejection
or by calculating isovolumic phase indices by known algorithms. The
primary calculations involve: (1) the time rate of change in
pressure or volume, dP/dt or dV/dt, as isovolumic indicators of
contractility; (2) ejection fraction as an ejection phase index of
cardiac function according to the known quotient of stroke volume
divided by end diastolic volume; (3) Maximal elastance, E.sub.M;
(4) regression slope through maximal pressure-volume points as a
further ejection phase index of contractility using the method of
Sagawa; (5) stroke work according to the known pressure-volume
integration; (6) the time course of minimum (end) diastolic
pressure-volume measurements according to the method of Glantz as a
measure of diastolic function; and (7) cardiac output calculation
according to the known product of heart rate and stroke volume as
an index of level of global function.
[0014] While measurement and storage of this group of parameters of
cardiac function and contractile state can provide valuable
information about the state of heart failure, there are other
parameters that of even greater value. Momentary changes to a
patient's autonomic state can change blood pressure (P), heart
rate, and pressure rate of change (dP/dt) contractility measures
and not be reflective of a "true" functional state change of the
heart. Such momentary changes in autonomic state are caused by
excitement and postural changes as noted in the above-referenced
'949 patent and other movements, such as bending down to pick up an
object or suddenly standing up from a sitting or reclining
position. It would be desirable to obtain cardiac data that
provides an enhanced assessment of cardiac contractile dysfunction
state (rather than a measure of pulmonary edema as in the '949
patent) that are less sensitive to such patient mental states,
movements and posture changes by enhanced signal processing of
relatively simple to measure cardiac signals and states.
[0015] Preferably, the parameter data is associated with a date and
time stamp and with other patient data, e.g., patient activity
level, and the associated parameter data is stored in implantable
medical device (IMD) memory for retrieval at a later date employing
conventional telemetry systems. Incremental changes in the
parameter data over time, taking any associated time of day and
patient data into account, provide a measure of the degree of
change in the condition of the heart.
BACKGROUND OF THE INVENTION
[0016] Millions of patients in the U.S. have been diagnosed with
heart failure. Heart failure (HF) is not a specific disease, but
rather a compilation of signs and symptoms, all of which are caused
by an inability of the heart to appropriately increase cardiac
output during exertion. HF may be caused by chronic hypertension,
ischemia, tachyarrhythmias, infarct or idiopathic cardiomyopathy.
The cardiac diseases associated with symptoms of congestive failure
include dilated cardiomyopathy, restrictive/constrictive
cardiomyopathy, and hypertrophic cardiomyopathy. The classical
symptoms of the disease include shortness of breath, edema, and
overwhelming fatigue. As the disease progresses, the lack of
cardiac output may contribute to the failure of other body organs,
leading to cardiogenic shock, arrhythmias, electromechanical
dissociation, and death.
[0017] Delivering pacing during the refractory period is a type of
non-excitatory stimulation (NES) that causes the release of
catecholamines such as norepinephrine within the tissue of the
heart. This chemical release results in an increased contractility
of the cardiac tissue, which in turn, results in increased cardiac
output, fewer symptoms of heart failure and improved exertional
capacity.
[0018] The treatment of severe cardiac dysfunction and
decompensated heart failure may include inotropic drug therapies
such as the catecholamines dopamine and dobutamine or
phosphodiesterase inhibitors milrinone or amrinone. Although these
agents may be beneficial in specific settings, they require
administration of a drug, often by intravenous route, with systemic
side effects and the time-consuming involvement of skilled
clinicians. Electrical stimulation therapies are attractive
alternatives because they may be administered by implanted or
external devices very shortly after dysfunction appears or worsens
and because their actions may be confined to the heart.
[0019] Delivering stimulation during the refractory period is a
type of non-excitatory stimulation (NES) also denoted herein as
refractory period stimulation (RPS) causes release of
catecholamines such as norepinephrine within the tissue of the
heart. This chemical release (modulated or regulated as described
herein) results from selective electrical stimulation of innervated
portions of the myocardial substrate. Because the electrical
stimulation is delivered during the non-excitatory or refractory
period wherein the discrete myocytes cannot contract, only the
interstitial nerve fibers effectively receive stimulation. This
results in increased contractility of the cardiac tissue which, in
turn, results in increased pressure or flow, fewer symptoms of
heart failure, and improved exertional capactity. NES
neurostimulation employs one or more pulses applied shortly after a
sensed depolarization or an initial pacing pulse is delivered and a
resulting ventricular contraction occurs. These NES pulses are
delivered during the refractory period of the cardiac tissue such
that they do not result in another mechanical contraction or
electrical depolarization.
[0020] Another type of electrical stimulation can be provided
during the nonrefractory period of the cardiac cycle. This type of
stimulation results in an additional electrical depolarization and,
when appropriately timed, results in post extrasystolic
potentiation (RPS). The additional depolarization, coming shortly
after a first depolarization, is likely not associated with a
sizable mechanical contraction. The contractility of subsequent
cardiac cycles is increased as described in detail in commonly
assigned U.S. Pat. No. 5,213,098. The mechanism is understood to
depend on calcium cycling within the myocytes. The early
extrasystole tries to initiate calcium release from the
sarcoplasmic reticulum (SR) too early and as a result does not
release much calcium. However, the SR continues to take up further
calcium with the result that the subsequent cardiac cycle causes a
large release of calcium from the SR and the myocyte contracts more
vigorously. Excitatory RPS stimulation requires an extra electrical
depolarization that is accompanied by a small mechanical
contraction.
[0021] Another known treatment for HF patients involves using
atrioventricular (AV) synchronous pacing systems, including DDD and
DDDR pacing devices, cardiac resynchronization therapy (CRT)
devices, and defibrillation systems, to treat certain patient
groups suffering heart failure symptoms. These systems generally
pace or sense in both the right atrium and right ventricle to
synchronize contractions and contribute to ventricular filling.
Cardiac resynchronization devices extend dual chamber pacing to
biventricular pacing to achieve better filling and a more
coordinated contraction of the left and right ventricles. These
pacing therapies result in greater pulse pressure, increased dP/dt,
and improved cardiac output. However, determining the appropriate
pacing parameters is difficult. For example, optimizing the length
of the AV delay requires obtaining pressure data involving an
extensive patient work-up as set forth in commonly assigned U.S.
Pat. No. 5,626,623. These pacing systems may also include atrial
and ventricular defibrillators or other therapies for
tachyarrhythmias. As a direct result of a tachycardia or as a
sequela, cardiac function may deteriorate to the point of greatly
reduced cardiac output and elevated diastolic pressure. Rapid
termination of tachycardias prevents worsening of heart
failure.
[0022] The above-described therapies, including pacing, CRT, NES,
and defibrillation capability, may be used alone or in combination
to treat cardiac dysfunction including HF. However, prior art
systems have not achieved a comprehensive therapy regimen that
coordinates these mechanisms in a manner that is both safe and
effective. Delivery of electrical stimulation as the heart tissue
is becoming non-refractory can trigger a tachyarrhythmia. This is
particularly true if multiple high-amplitude pacing pulses are
utilized. A second problem may be a shift in the magnitude of
resulting potentiation or refractory interval due to the course of
disease or medication. These may lead to unacceptable levels of
potentiation performance, or loss of effect altogether. Therefore,
readily obtaining the appropriate timing parameters associated with
this type of therapy is essential.
[0023] What is needed is a system and method that combines the
known therapies available for treating cardiac dysfunction
including HF in a manner that optimizes mechanical function or
cardiac output, while also minimizing any risks associated with
possibly inducing an arrhythmia.
[0024] As discussed herein and in the related,
incorporated-by-reference applications, an RSP therapy involves
providing one or more pulses (e.g., one to a plurality of
electrical pulses having programmable values, such as for instance
50 Hz pulse(s) with a pulse amplitude of 4-10 volts, nominal pulse
width of 1 to 3 ms) during the refractory period of at least one
ventricle. The pulses are delivered such that the ventricles do not
experience a second depolarization following delivery of the
pulse(s). The RPS therapy increases contractile function and stroke
volume on subsequent contractions. The magnitude of the enhanced
function is dependent on simulation timing, location, waveform
characteristics, duration and frequency of RPS therapy delivery and
the like. The delivery location can include multi-site locations
within one or both ventricles (or via a coronary vein, a
pericardial location, and/or single ventricular sites. The pulse or
pulses can be bi-polar or uni-polar and the vectors of said
pulse(s) can vary between any available electrodes.
SUMMARY OF THE INVENTION
[0025] The current invention provides a system and method for
delivering therapy for cardiac hemodynamic dysfunction, which
without limitation, may include one of the following features:
[0026] Therapy for cardiac dysfunction that might otherwise require
inotropic drugs such as dobutamine, calcium, or milrinone;
[0027] Therapy for cardiac dysfunction that might otherwise require
mechanical aids such as intra-aortic balloon pumps, cardiac
compression devices, or LV assist device pumps;
[0028] An implantable or external device that continuously monitors
the patient, automatically administering therapy when physiologic
sensors indicate need or the patient experiences symptoms;
[0029] Treatment for cardiac dysfunction as a result of drug
overdose or hypothermia; Combined with negative inotrope drug
treatments such as beta blockers to improve patient tolerance of
these treatments;
[0030] Therapy for post ischemic cardiac dysfunction or stunning
such as following coronary vessel occlusion, thrombolytic drugs,
angioplasty, or cardiac bypass surgery;
[0031] Support for the dysfunction that is associated with coming
off cardiac bypass and the use of cardioplegia;
[0032] Therapy for rapid and poorly tolerated supra-ventricular
tachycardias (SVT) by regularizing 2:1 AV block, lowering
mechanical heart rate and improving mechanical function, and may
facilitate arrhythmia termination;
[0033] Management of dysfunction following tachycardic events
including AT, AF, SVT, VT, or VF including elective cardioversion
and urgent defibrillation and resuscitation;
[0034] Severe bouts of heart failure, worsening to cardiogenic
shock, electromechanical dissociation (EMD) or pulseless electrical
activity (PEA)
[0035] Acute deterioration of cardiac function associated with
hypoxia or metabolic disorders;
[0036] Intermittent therapy for HF such as prior or during exertion
or for worsening symptoms;
[0037] Continuous therapy for HF to modify heart rate, improve
filling and mechanical efficiency, and facilitate reverse
remodeling and other recovery processes;
[0038] Scheduled therapy for HF including use for a specified
interval of time at a particular time of day or scheduled delivery
every N cardiac cycles; and/or
[0039] Reducing AF burden as a result of reduced atrial loading and
better ventricular function during therapy
[0040] Overview of a System Operating According to the Present
Invention
[0041] A system constructed and operated according to the present
invention that may be used to deliver the therapies discussed above
may include a signal generator, timing circuit, and/or
microprocessor control circuit of the type included in existing
pacemaker or ICD systems as is known in the art. Exemplary systems
are shown in U.S. Pat. Nos.5,158,078, 5,318,593, 5,226,513,
5,314,448, 5,366,485, 5,713,924, 5,224,475 and 5,835,975 each of
which is incorporated herein by reference, although any other type
of pacing and/or ICD system may be used for this purpose. In such
systems, EGM sensing is performed by electrodes carried on leads
placed within the chambers of the heart, and/or on the housing of
the device. Alternatively, subcutaneous and/or external pad or
patch electrodes may be used to sense cardiac signals.
Physiological sensors may likewise be carried on lead systems
according to any of the configurations and/or sensing systems known
in the art.
[0042] The following introductory material is intended to
familiarize the reader with the general nature and some of the
features of the present invention.
[0043] Brief Description of Electrodes and Leads for Use with the
Present Invention.
[0044] All embodiments of the present invention share a common need
for electrode configurations to deliver electrical stimulation
energy where necessary and to time the delivery of this energy to
achieve beneficial effects while avoiding unsafe delivery (as
further described hereinbelow). For each therapy component
described above, specific electrode locations and geometries may be
preferred. The locations for the electrodes of this invention for
stimulation include: use of large surface area defibrillation coil
electrodes in the heart or adjacent to the heart; pacing electrodes
at locations including RV apex, outflow tract, atrial locations,
HIS bundle site, left side epicardium, pericardium or endocardium;
sympathetic nerve regions near the cervical or thoracic spine or
nerves or adjacent vessels on or near the heart; transthoracic
electrodes including paddles and patches, can electrode, temporary
electrodes (e.g., epicardial, transvenous or post-operative
electrodes), subcutaneous electrodes and multiple site
stimulation.
[0045] In accordance with common biomedical engineering practices,
stimulation therapy is applied with minimized net charge delivery
to reduce corrosion and counteract polarization energy losses. Both
energy efficient therapy delivery and electrogram (EGM) sensing
benefit from low polarization lead systems. Finally, the electrodes
are preferably connected to fast recovery amplifiers that allow EGM
sensing soon after therapy delivery.
[0046] Brief Description of Sensors for Use with the Present
Invention.
[0047] The most fundamental sensors are those based on electrograms
(ECG or EGMs) and reflect cardiac electrical activity. These
sensors require electrodes located where they can readily detect
depolarization and repolarization signals as well as sense
amplifiers for the monitoring of heart rhythm and diagnosis of
arrhythmias.
[0048] According to one embodiment, blood pressure sensors,
accelerometers, flow probes, microphones, or sonometric crystals
may be used to measure flow, force, velocity, movement of the walls
of the heart, and/or to estimate the volume of the cardiac
chambers. Parameters derived from these sensors can also be used to
detect the onset and severity of cardiac hemodynamic dysfunction.
For example, HF decompensation may be indicated when a change in
long-term diastolic cardiac pressure has increased while
contractility of the heart derived from dP/dt rate of rise of
ventricular pressure has diminished.
[0049] Another embodiment of the invention may utilize changes in
transthoracic or intracardiac impedance signals to sense cardiac
motion and respiratory movement. Changes in intra-thoracic
impedance as a result of pulmonary edema may also be used trigger
RPS and/or NES stimulation therapy.
[0050] In implantable or external devices, metabolic or chemical
sensors such as expired CO.sub.2 and blood oxygen saturation, pH,
pO.sub.2, and/or lactate) may be employed to reflect cardiac
dysfunction.
[0051] Brief Description of Atrial Coordinated Pacing ("ACP")
According to the Invention.
[0052] According to one form of the invention, electrical
stimulation to the upper and/or lower chambers of the heart may be
delivered both during refractory and non-refractory periods to
coordinate atrial contraction, stabilize the rhythm, and optimize
cardiac output. This stimulation is implemented via the present
invention in a manner that minimizes the dangers associated with
induced arrhythmias. Intrinsic atrial events are followed by
ventricular events and manifest as sharp deflections of atrial and
ventricular electrograms ("AEGMs" and "VEGMs," respectively).
[0053] According to one form of the invention, pacing occurs in the
atrium at a rate that is higher than the intrinsic rate. Even
though 2:1 conduction is still present, the intrinsic ventricular
depolarizations occur more frequently because of the increased
atrial rate. Yet another waveform "D" can be used to illustrate
another form of ACP which the inventors consider a special case of
ACP. In this case, an atrial coordinated pace is initiated a
relatively short time period following a ventricular (or atrial)
beat. Because of the AV block and the refractory state of the
ventricles, this Acp paced event does not conduct to the ventricle.
Following this ACP paced beat an intrinsic depolarization is
allowed to occur in the atrium (As). This intrinsic beat conducts
to the ventricle, resulting in a ventricular depolarization
(Vs).
[0054] This aspect of the present invention allows a patient's
natural AV conduction and intrinsic rate to emerge during the
cardiac cycle, providing better rate control during RPS therapy.
Extensions to provide a lower rate limit by atrial and/or
ventricular pacing are well known in the art of pacing. ACP may be
provided by an implantable device as illustrated here or be
provided by transcutaneous pacing (TCP) stimulation timed from the
surface ECG's R wave by stimuli of sufficient amplitude to capture
both atria and ventricles.
[0055] Brief Description of NES/Sympathetic Neurostimulation per
the Invention.
[0056] According to another aspect of the invention, non-excitatory
electrical neural stimulation therapies are directed at sympathetic
nerves in the neck, chest, mediastinum, and heart to enhance
mechanical function by local release of catecholamines, such as
norepinephrine. These therapies are known as nonexcitatory
electrical stimulation (NES) therapies because they are not
intended to cause cardiac tissue depolarization and can be
accomplished with electrode locations and stimulation timing that
avoid electrically exciting cardiac tissue. Electrodes near the
heart deliver one or more NES pulses within the refractory period
of the myocardium. Of course, electrodes that direct electrical
current away from the myocardium may deliver electrical stimuli at
various times throughout the cardiac cycle without directly
exciting cardiac tissue.
[0057] Brief Description of Safety Lockout Rule(s) per the Present
Invention.
[0058] Another aspect of the invention involves delivering
electrical stimulation to the atrium and ventricles in a manner
that optimizes resulting mechanical function including pressures
and flows while minimizing associated risks. Several features of
the present invention are provided to achieve this goal, including
regulation of NES and RPS therapy delivery to attain the desired
level of enhanced function, the use of atrial coordinated pacing,
or ACP , to improve rhythm regularity and hemodynamic benefit over
NES and/or RPS alone, and a safety rule to inhibit or lockout RPS
therapy when it is at risk of being proarrhythmic, diminishing
diastole and coronary blood flow, and/or reducing the beneficial
effect on hemodynamics. Rapid heart rates are prime examples of
when RPS therapy is counter productive and motivate use of a safety
lockout rule.
[0059] A safety lockout rule operates on a short term or
beat-by-beat basis to disable RPS (and ACP, if enabled) if the V-V
interval from the prior cycle is too short. Thus, ectopy will
suppress RPS therapy as will sinus tachycardia, other SVTs, VTs,
and VF. The inventors have discovered that this rule is a key
component of safe and effective RPS stimulation therapy in a
variety of situations.
[0060] Brief Description of Therapy Start and Stop Rules per the
Invention.
[0061] The application of RPS and NES therapy according to the
present invention may be altered by (i) a physician (based on
laboratory results and the patient's signs and symptoms), (ii) by
the patient (to help with anticipated or present symptoms such as
associated with exertion), or (iii) automatically by device sensors
that detect conditions responsive to these stimulation therapies.
In each of these cases there may be distinct maximal therapy
durations and termination criteria (or therapy may be ended by the
physician or patient).
[0062] Automated sensor-governed initiation of stimulation
therapies are described herein. If there is no current arrhythmia,
physiologic sensors are employed to determine if cardiac
hemodynamic dysfunction therapy is to be initiated. Blood pressure
signals such as arterial, right ventricular, and/or left
ventricular pressure sensors (which may be utilized to derive other
discrete cardiovascular pressure measurements) may be used to
obtain respective pressure measurements. Therapy may be initiated
when these measurements indicate a pressure change that drops below
or exceeds a predetermined threshold for an established period of
time. In one example depicted in detail herein, a severe level of
dysfunction (LV dP/dt max<400 mmHg/s) is observed during normal
sinus rhythm for over six seconds. The pressure measurements may be
weighted and/or combined to obtain a statistic used to trigger
therapy delivery. The statistic may be used to develop long-term
trend data used to indicate the onset and severity of HF and
hemodynamic dysfunction.
[0063] In another aspect of the invention, RV pressure is used to
derive RV end-diastolic and developed pressure, maximum pressure
change as a function of time (dP/dtmax), an estimate of pulmonary
artery diastolic pressure (ePAD), an RV relaxation or contraction
time constant (tau), or RV recirculation fraction (RF). These
derived parameters are then used to determine when the degree of
dysfunction has exceeded an acceptable level such that therapy
delivery is initiated. Parameters could be measured or computed as
above and compared to thresholds, or sensor signals could be
processed and cardiac dysfunction identified through template
matching and classification. Thresholds and/or classification
schemes may be periodically updated to reject any natural changes
in the condition of the patient as cause for therapy.
[0064] The present invention may also incorporate predicted
hemodynamic compromise through an extended analysis of cardiac
cycle-length. For example, a long duration and rapid SVT, VT, or VF
has a high likelihood of producing dysfunction including acute HF
decompensation, cardiogenic shock, or even electromechanical
dissociation (EMD) or pulseless electrical activity (PEA) after
spontaneous termination or cardioversion. In such cases, a trial of
stimulation therapy might be programmed without mechanical,
metabolic, or chemical sensor confirmation.
[0065] Other signals such as surface electrocardiogram (ECG) or
electrogram (EGM) signals from electrodes within the patient's body
may be used to detect dysfunction and heart failure (HF). For
example, the ST segment level of a cardiac cycle (PQRST) detected
by an ECG may be monitored. An elevated or depressed ST segment
level has been found to be reliable indicator of ischemia, a
condition known to be associated with dysfunction and HF.
Alternatively, the duration of the Q-T interval may also be used to
detect hemodynamic dysfunction. For example, a shortened Q-T
interval may indicate myocardial dysfunction. A template matching
algorithm such as a wavelet classification algorithm may be used to
identify electrogram signals that are associated with hemodynamic
dysfunction.
[0066] Chemical sensors may be used to initiate therapy, including
sensors that analyze the blood to detect changes in lactate,
O.sub.2 saturation, PO.sub.2, PCO.sub.2 and pH. Expired gas may be
analyzed for PCO.sub.2 as an indicator of cardiac output during
resuscitation procedures. Pulse oximetry may provide noninvasive
assessments of oxygen saturation and pulse plethysmogram signals
which have particular utility in the context of applying the
inventive cardiac therapy with an automatic external defibrillator
(AED) following cardioversion of a tachyarrhythmia. Therapy is then
continued until the degree of dysfunction or HF reflected by these
variables is less than a predetermined amount for a sufficient
period of time.
[0067] Although pressure sensors figure prominently in the examples
above (and in the '631 disclosure) a number of other sensors could
reflect mechanical function. Intracardiac or transthoracic
impedance changes reflect mechanical function, stroke volume, and
cardiac output. Accelerometers or microphones within the body or
applied externally sense serious cardiac dysfunction and monitor
the response to therapy. Heart volume, dimension changes, and
velocities may be measured by implanted or external applications of
ultrasound.
[0068] Physiologic signals may continue to be sensed to determine
if a therapy termination condition is met so that therapy may be
terminated. In the context of an AED, for example, this may involve
determining that a tachyarrhythmia has terminated and that arterial
pulse pressure has reached levels compatible with recovery. The
use, however, of a mechanical sensor such as a pressure sensor or
an accelerometer to determine whether or not to apply therapy has
the drawback in that external treatments of PEA/EMD such as cardiac
chest compressions may introduce error into the physiologic
signals, inhibiting or delaying therapy when it may be needed. An
additional aspect of the invention is to include not only a
mechanical sensor in or on the heart to detect cardiac function,
but a second sensor or a multitude of sensors away from the heart,
such as inside the implantable device housing or can (acting as an
indifferent electrode). From this second sensor, CPR artifact (due
to chest compressions and the like) could be identified and
subtracted to reveal a more accurate assessment of true cardiac
function.
[0069] Therapy is ordinarily automatically interrupted on detection
of an arrhythmic event. Upon termination of the arrhythmic event,
the therapy may be automatically reconfigured to reduce risk of
re-induction. Therapy could also be interrupted on detection of a
sufficient quantity of abnormal depolarizations such as a premature
ventricular contraction (PVC). One or more PVCs could be detected
through the use of rate limits or through a template matching type
algorithm such as a template matching algorithm like a wavelet
classification algorithm, or using a PR-logic.RTM. type rhythm
discrimination scheme which is a proprietary detection technique of
Medtronic, Inc.
[0070] Brief Description of Identifying the Refractory Interval per
the Invention.
[0071] Although beneficial for cardiac function, the delivery of
RPS stimulation pulses must be controlled so as to minimize the
risk of inducing an arrhythmia. This is best realized with
reference to the traces of an ECG or EGM signal aligned with a
stimulus-intensity curve to show the intensity of pulses required
to induce an extra systole during the time period following a
ventricular depolarization which coincides to the QRS complex at an
initial time zero (0). During the absolute refractory period, the
ventricles are refractory so that another depolarization will not
be induced by delivery of electrical stimulation either directly or
by applying electrical stimulation to an atrial chamber. Following
this time, the tissue recovers so that another electrical
depolarization is possible upon the delivery of electrical
stimulation to the cardiac tissue. The amount of electrical current
required to cause the extra systole during this time is represented
by the stimulus-intensity curve.
[0072] Initially the electrical current level required to capture
the tissue is high but thereafter sharply decreases to a baseline
level of roughly 0.5-1 mA for an implanted pacing lead. For TCP via
electrode pads or paddles of an AED or external defibrillator the
baseline level may be on the order of 50-100 mA.
[0073] Also, the "vulnerable period" of the ventricles must be
considered when administering RPS therapy. The vulnerable period
represents a time period during which an electrical pulse delivered
at, or above, a pre-determined amplitude has the risk of causing a
VT or VF episode. For example, a pulse delivered at about 170 ms
having an amplitude of 40 mA or more may induce an
tachyarrhythmia.
[0074] The importance of identifying and techniques for identifying
the refractory-nonrefractory boundary is described herein.
Nonexcitatory neurostimulation benefits arise from pulses anywhere
in the refractory period. NES neurostimulation delivered outside
the refractory period is frequently excitatory (and will be
addressed in the excitatory RPS analysis which follows herein
below).
[0075] The level of enhancement or potentiation resulting from
excitatory RPS stimulation therapy follows a potentiation response
curve as further described herein. The inventors have found that
such electrical stimulation pulses delivered shortly after the
refractory period ends produce strong subsequent contractions.
Further delays of the stimulation diminish the amount of
potentiation. Stimulation too early (i.e., prematurely) results in
no additional potentiation at all since the myocardium is
refractory. As discussed with respect to the vulnerable period, the
risk of arrhythmia induction is confined to a relatively narrow
time interval just slightly longer than the refractory period.
However, the inventors have discovered that such a risk is quite
low if single RPS pulses are delivered according to the safety
lockout rule (briefly described above).
[0076] As a result, it is apparent that stimulation timing with
respect to the refractory-nonrefractory period boundary is a
critical aspect of obtaining the desired response (NES or RPS) and
controlling risks and benefits of therapy delivery. The present
invention provides for means to determine this time from
electrical, and/or mechanical sensor signals and thereby enable
safer and more effective stimulation therapies.
[0077] The inventors exploit the fact that the refractory period is
closely associated with the Q-T interval, which may be derived from
electrogram signals or other physiologic sensor signals by
techniques known in the art. The Q-T interval length is used to
estimate the duration of the refractory period either directly, or
by incorporating a function of heart rate and sensing delays. In
the case of RPS therapy, the Q-T interval length can be estimated
by the time interval from an extra systole stimulation pulse to an
evoked T wave and would be slightly longer than during a cardiac
cycle not associated with PESP. This is because the extra
depolarization caused by the RPS prolongs the QT interval
slightly.
[0078] Alternatively, an evoked response of the RPS stimulation
could be monitored to indicate whether the RPS therapy was
delivered in the refractory period or not. For example, a number of
electrical pulses are applied to the myocardium, beginning during
the refractory period. The result of each pulse is sensed on an EGM
from either the stimulating electrode or an auxiliary electrode
until an evoked response is sensed, indicating that the pulse
caused an extra systole. At this point, no further pulses would be
applied to minimize the risk of inducing arrhythmias.
[0079] In another example, a single pulse's amplitude and timing
may be manipulated until capture is detected by an evoked R wave.
If capture is lost, the stimulus pulse is delayed more, or
amplitude increased, or the number of pulses in a RPS pulse train
is increased. Also, the characteristics of a pressure waveform (or
any other mechanical response variable) used to assess whether the
RPS stimulation is/was capturing the ventricles can be utilized
when practicing the present invention. The presence of the extra
systole could be identified by a small ventricular pressure pulse
5-80% of the size of the preceding pressure pulse or through a
suitable algorithm such as a template matching algorithm.
[0080] The inventive system may also deliver optional
non-excitatory neurostimuli using a waveform including one or more
pulses during the refractory period. To ensure that the NES
stimulation does not enter the vulnerable period, the length of the
refractory period is estimated using the mechanisms discussed
above. If NES is exclusively intended, then detection of an extra
systole--due to a capturing pulse delivered outside the refractory
period--should result in a reduction of the stimulus delay time,
amplitude, or pulse number.
[0081] As the refractory-nonrefractory boundary is very important
and varies from patient to patient and even with a patient over
time, with disease and drugs, these methods are to be employed
periodically or continually to the stimulation timing algorithm
portion of the device. If this boundary information is not used to
set pulse timing directly, it may be employed to establish limits
for the timing that is in turn set by a clinician or some automatic
control algorithm such as that described next.
[0082] Brief Description of Feedback Control of Stimulation Therapy
per the Invention.
[0083] According to yet another aspect of the invention,
closed-loop feedback from physiologic sensors is used to adjust the
timing of the electrical stimulation so that therapy delivery may
be tuned to further optimize cardiac function, maintain safety, and
accommodate variations in the heart's responsiveness. The basic
nonexcitatory neurostimulation (NES) response curve (a function of
stimulus intensity in the refractory period). Changes from patient
to patient or within a patient (over time) may lead to different
levels of enhanced function for a fixed NES stimulus. Conversely,
maintenance of a desired level of enhancement may require different
stimulation times or intensities.
[0084] Sensor signal feedback may be used to govern stimulation
timing in a closed loop fashion to accommodate variations in
responsiveness. A physician may react to physiologic information
and adjust the electrical stimulation amplitude and timing. In the
alternative, this reaction may be accomplished by the device
according to an algorithm referred to as a controller. An
elementary but useful and widely used family of controllers is
referred to as PID or P+I+D control. PID controllers work with an
error signal that reflects how far the sensor level is from a
target level or setpoint. The controller's output is a combination
of the error signal, the integral of the error, and the derivative
of the error each scaled by a constant denoted P, I, and D,
respectively. Practical controllers incorporate limits on their
outputs and integrators so as to keep the input to system they
influence (called a plant) within reasonable bounds and maintain
responsiveness.
[0085] An illustration of a functioning P+I controller based on RV
dP/dtmax is disclosed herein for use in conjunction with the
present invention. As an example, a setpoint of 700 mmHg/s was
chosen for RPS stimulation from a baseline of 280 mmHg/s and the
controller and therapy begun. The RPS stimulation pulse was
automatically adjusted each cardiac cycle based on the P+I
controller within upper and lower limits. In the course of our
research we increased the controller's gains which led to
oscillation. Using less gain it was possible to trade a little
sluggishness in response for a great deal of robustness to
variations in the plant's response by exploiting feedback
control.
[0086] It may be noted that stimulation time, as well as the
maximum amplitude, pulse intervals, number of pulses in a train,
change in the amplitude of sequential pulses in the pulse train,
and other parameters may be adjusted to achieve optimal cardiac
performance for a given patient. This may be accomplished by
monitoring sensed physiologic parameters in a closed-loop manner.
The pulse train may then be adjusted accordingly to maximize
cardiac output or other indices of physiologic function. For
example, rather than altering the timing of a single RPS pulse, the
controller may alter the number and duration of a pulse train.
[0087] The NES stimulation may also be modulated to further improve
cardiac function using physiologic signal monitoring in a
closed-loop environment very similar to that discussed above for
RPS therapy. The various pulse trains found to be most effective
for use in NES and RPS therapies are described in more detail in
the related applications incorporated herein. The number of pulses,
pulse amplitude, pulse shape, and any other aspect of the signal
may be varied based on physiologic measurements to maximize cardiac
output. Both the NES and RPS pulse trains may be optimized to
achieve maximum cardiac function. Both NES and RPS therapies need
not be applied every cardiac cycle but could skip a specific number
of cycles between applications (e.g., for one hour out of every six
hours, manually triggered by a patient, triggered based on detected
physiologic state of a patient such as high or variable heart rate,
etc.). The number of cycles skipped could also serve as a control
variable.
[0088] Brief Description of Extensions to Tachyarrhythmia
Management Devices.
[0089] An additional aspect of this invention is to change existing
regimens for the delivery of anti-tachycardia pacing (ATP) and
shocks for cardioversion and defibrillation, given that cardiac
stimulation therapy may be activated following these therapies. A
flowchart illustrating this aspect of the invention appears herein
and is applicable for both ICDs (implantable cardiovertor
defibrillators) and AEDs (automated external defibrillators).
[0090] The first change to existing and prior art regimens is to
increase the number of shocks beyond the present upper limit.
[0091] A second change is to increase the time between the later
shocks in the sequence. With greater spacing, higher detection
specificity would be possible and minimize the potential risk of
shock-induced myocardial damage.
[0092] A third change would be to monitor the EGM for increased
regularity and/or increased amplitude which may be an indicator as
to when it would be most efficacious to deliver the extra
shocks.
[0093] An additional aspect of this invention is to modify existing
rhythm recognition algorithms of implanted and external therapy
devices to accommodate operating concurrently with therapy pulses
delivered by a preexisting external or implanted device
respectively. The sharp changes in electrogram slew rate associated
with stimulation pulses may be recognized and ignored for the
purpose of automated rhythm recognition. The devices analyze the
effective heart rate and rhythm accordingly and do not falsely
detect or treat tachyarrhythmias.
[0094] Brief Description of a System Comprising the Present
Invention.
[0095] A comprehensive flowchart depicting a high level view of the
present invention showing the integration significant aspects for
non-excitatory RPS stimulation is included herewith. A
representative heart and cardiovascular system is influenced by
electrical therapies including pacing, defibrillation, CRT, RPS
and, optionally, NES stimulation therapy. The heart and
cardiovascular system may be monitored by electrical, mechanical,
and metabolic/chemical sensors. The signals from these sensors
influence decisions to start or stop therapy, closed loop control,
refractory period detection, therapy safety lockout rules, and
atrial coordinated pacing.
BRIEF DESCRIPTION OF THE DRAWINGS
[0096] These and other advantages and features of the present
invention will be more readily understood from the following
detailed description of the preferred embodiments thereof, when
considered in conjunction with the drawings, in which like
reference numerals indicate identical structures throughout the
several views. The drawings are not drawn to scale and do not
necessarily include all elements of every embodiment of the present
invention.
[0097] FIG. 1 depicts the relationship of heart chamber EGM,
pressure, flow, and volume during a cardiac cycle.
[0098] FIG. 2 is a schematic diagram depicting a multi-channel,
atrial and bi-ventricular, monitoring/pacing IMD in which the
present invention is preferably implemented.
[0099] FIG. 3 is a simplified block diagram of one embodiment of
IPG circuitry and associated leads employed in the system of FIG. 1
enabling selective therapy delivery and heart failure state
monitoring in one or more heart chamber.
[0100] FIG. 4 is a simplified block diagram of a single monitoring
and pacing channel for deriving pressure, impedance and cardiac EGM
signals employed in monitoring HF and optionally pacing the heart
and delivering RPS therapy in accordance with the present
invention.
[0101] FIG. 5 depicts the delivery of therapeutic RPS stimulation,
particularly, pacing energy pulse trains commenced during the
refractory period of the heart and continuing for a RPS delivery
interval.
[0102] FIG. 6 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0103] FIG. 7 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0104] FIG. 8 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0105] FIG. 9A through 9D are simple exemplary timing diagrams of
various embodiments of the therapy delivery according to the
present invention.
[0106] FIG. 10 is a perspective view with portions exploded (and
with some portions not depicted) of a heart and related sympathetic
nerves which may be advantageously stimulated according to certain
embodiments of the present invention.
[0107] FIG. 11 is a depiction of neurostimulation timing for
electrodes disposed near the cardiac tissue and relatively remotely
from the cardiac tissue of a patient.
[0108] FIG. 12 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0109] FIG. 13 is a set of three X-Y plots representing physiologic
and therapy activity according to the present invention.
[0110] FIG. 14 is a flow chart depicting an aspect of the present
invention.
[0111] FIG. 15 is a flow chart depicting another aspect of the
present invention.
[0112] FIG. 16 is a flow chart depicting yet another aspect of the
present invention.
[0113] FIG. 17 is a flow chart depicting an additional aspect of
the present invention.
[0114] FIG. 18 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0115] FIG. 19 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0116] FIG. 20 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0117] FIG. 21 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0118] FIG. 22 is a flow chart depicting an additional aspect of
the present invention.
[0119] FIG. 23 is a set of four X-Y plots illustrating timing
relationships between stimulation amplitude, mechanical function,
arrhythmia risk and "net benefit" of therapy delivery according to
the present invention.
[0120] FIG. 24 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0121] FIG. 25 is a set of traces representing physiologic and
therapy activity according to the present invention.
[0122] FIG. 26 is a flow chart depicting an additional aspect of
the present invention.
[0123] FIG. 27 is a flow chart depicting an additional aspect of
the present invention.
[0124] FIG. 28 is a flow chart depicting an additional aspect of
the present invention.
[0125] FIG. 29 is a pair of X-Y plots showing the relationship
between mechanical function (dP/dtmax) as a function of time and
stimulation intensity, respectively.
[0126] FIG. 30 is a pair of X-Y plots showing the relationship
between mechanical function (dP/dtmax) as a function of time and
stimulation intensity, respectively.
[0127] FIG. 31 is a flow chart depicting an additional aspect of
the present invention.
[0128] FIG. 32 is a flow chart depicting an additional aspect of
the present invention.
[0129] FIG. 33 is a set of plotted empirical data representing
physiologic and therapy activity according to the present
invention.
[0130] FIG. 34 is a flow chart depicting an additional aspect of
the present invention.
[0131] FIG. 35 is a flow chart depicting an additional aspect of
the present invention.
[0132] FIG. 36 is a set of traces representing physiologic and
therapy activity according to the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0133] In the following detailed description, references are made
to illustrative embodiments for carrying out the invention. It is
understood that other embodiments may be utilized without departing
from the scope of the invention.
[0134] efore describing the preferred embodiments, reference is
made to FIG. 1 reproduced from the above-referenced '464 patent
which depicts the electrical depolarization waves attendant a
normal sinus rhythm cardiac cycle in relation to the fluctuations
in absolute blood pressure, aortic blood flow and ventricular
volume in the left heart. The right atria and ventricles exhibit
roughly similar pressure, flow and volume fluctuations, in relation
to the PQRST complex, as the left atria and ventricles. It is
understood that the monitoring and stimulation therapy aspects of
this invention may reside and act on either or both sides of the
heart. The cardiac cycle is completed in the interval between
successive PQRST complexes and following relaxation of the atria
and ventricles as the right and left atria re-fill with venous
blood and oxygenated blood. In sinus rhythm, the interval between
depolarizations may be on the order of 500.0 ms to 1,000.0 ms for a
corresponding sinus heart rate of 120 bpm to 60 bpm, respectively.
In this time interval, the atria and ventricles are relaxed, and
overall atrial size or volume may vary as a function of pleural
pressure and respiration. In the blood pressure diagrams of FIG. 1,
it may be observed that the atrial and ventricular blood pressure
changes track and lag the P-waves and R-waves of the cardiac cycle.
The time period T.sub.0-T.sub.1 encompasses the AV interval.
[0135] In patients suffering from cardiac insufficiency arising
from bradycardia due to an incompetent SA node or AV-block, atrial
and/or ventricular conventional pacing may be prescribed to restore
a sufficient heart rate and AV synchrony. In FIG. 1 for example,
atrial and/or ventricular pacing pulses would precede the P-wave
and the deflection of the QRS complex commonly referred to as the
R-wave. Cardiac output may be reduced by the inability of the
atrial or ventricular myocardial cells to relax following atrial
(T.sub.0-T.sub.i) and ventricular (T.sub.1-T.sub.2) systolic
periods. Prolonged systolic time periods reduce passive filling
time T.sub.4-T.sub.7 as shown in FIG. 1. Thus, the amount of blood
expelled from the atria and/or ventricles in the next cardiac cycle
may be less than optimum. This is particularly the case with HF
patients or other patients in whom the stiffness of the heart is
increased, cardiac filling during the passive filling phase
(T.sub.4-T.sub.7) and during atrial systole (T.sub.0-T.sub.1) is
significantly limited.
[0136] It will be appreciated from the following description that
the monitor/therapy delivery IMD of the present invention may be
utilized to obtain the aforementioned parameters as stored patient
data over a period of time and to deliver therapies for treating
the heart failure. The physician is able to initiate uplink
telemetry of the patient data in order to review it to make an
assessment of the heart failure state of the patient's heart. The
physician can then determine whether a particular therapy is
appropriate, prescribe the therapy for a period of time while again
accumulating the stored patient data for a later review and
assessment to determine whether the applied therapy is beneficial
or not, thereby enabling periodic changes in therapy, if
appropriate. Such therapies include drug therapies and electrical
stimulation therapies, including RPS and/or NES stimulation, and
pacing therapies including single chamber, dual chamber and
multi-chamber (bi-atrial and/or bi-ventricular) pacing. Moreover,
in patients prone to malignant tachyarrhythmias, the assessment of
heart failure state can be taken into account in setting parameters
of detection or classification of tachyarrhythmias and the
therapies that are delivered.
[0137] Accordingly, an embodiment of the invention is disclosed in
detail in the context of a multi-chamber pacing system that is
modified to derive the aforementioned parameters indicative of
cardiac mechanical dysfunction from sensors, sense electrodes and
electrical stimulation electrodes located in operative relation to
one or more heart chamber. This embodiment of the invention may be
programmed to operate as an AV sequential, bi-atrial and
bi-ventricular, pacing system operating in demand, atrial tracking,
and triggered pacing for restoring synchrony in depolarizations and
contraction of left and right ventricles in synchronization with
atrial sensed and paced events for treating HF and/or bradycardia.
This embodiment of the invention is therefore programmable to
operate as a two, three or four channel pacing system having an AV
synchronous operating mode for restoring upper and lower heart
chamber synchronization and right and left atrial and/or
ventricular chamber depolarization synchrony. However, it will be
understood that only certain of the components of the complex
multi-chamber pacing system described below can be selectively
programmed to function or physically only incorporated into a
simpler, single chamber, monitoring/stimulation system for deriving
the parameters indicative of heart failure state.
[0138] In FIG. 2, heart 10 includes the upper heart chambers, the
right atrium (RA) and left atrium (LA), and the lower heart
chambers, the right ventricle (RV) and left ventricle (LV) and the
coronary sinus (CS) extending from the opening in the right atrium
laterally around the atria to form the great vein that extends
further inferiority into branches of the great vein. The cardiac
cycle commences normally with the generation of the depolarization
impulse at the SA Node in the right atrial wall. The impulse then
conducts through the right atrium by way of Internodal Tracts, and
conducts to the left atrial septum by way of Bachmann's Bundle. The
RA depolarization wave reaches the Atrio-ventricular (AV) node and
the atrial septum within about 40 msec and reaches the furthest
walls of the RA and LA within about 70 msec. Approximately 50 ms
following electrical activation, the atria contract. The aggregate
RA and LA depolarization wave appears as the P-wave of the PQRST
complex when sensed across external ECG electrodes and displayed.
The component of the atrial depolarization wave passing between a
pair of unipolar or bipolar pace/sense electrodes, respectively,
located on or adjacent the RA or LA is also referred to as a sensed
P-wave. Although the location and spacing of the external ECG
electrodes or implanted unipolar atrial pace/sense electrodes has
some influence, the normal P-wave width does not exceed 80 msec in
width as measured by a high impedance sense amplifier coupled with
such electrodes. A normal near field P-wave sensed between closely
spaced bipolar pace/sense electrodes and located in or adjacent the
RA or the LA has a width of no more than 60 msec as measured by a
high impedance sense amplifier.
[0139] The depolarization impulse that reaches the AV Node conducts
down the bundle of His in the intraventricular septum after a delay
of about 120 msec. The depolarization wave reaches the apical
region of the heart about 20 msec later and is then travels
superiorly though the Purkinje Fiber network over the remaining 40
msec. The aggregate RV and LV depolarization wave and the
subsequent T-wave accompanying re-polarization of the depolarized
myocardium are referred to as the QRST portion of the PQRST cardiac
cycle complex when sensed across external ECG electrodes and
displayed. When the amplitude of the QRS ventricular depolarization
wave passing between a bipolar or unipolar pace/sense electrode
pair located on or adjacent to the RV or LV exceeds a threshold
amplitude, it is detected as a sensed R-wave. Although the location
and spacing of the external ECG electrodes or implanted unipolar
ventricular pace/sense electrodes has some influence on R-wave
sensing, the normal R-wave duration does not exceed 80 msec as
measured by a high impedance sense amplifier. A normal near field
R-wave sensed between closely spaced bipolar pace/sense electrodes
and located in or adjacent the RV or the LV has a width of no more
than 60 msec as measured by a high impedance sense amplifier.
[0140] The normal electrical activation sequence becomes highly
disrupted in patients suffering from advanced HF and exhibiting
Intra-atrial conduction delay (IACD), Left Bundle Branch Block
(LBBB), Right Bundle Branch Block (RBBB), and/or Intraventricular
Conduction Delay (IVCD). These conduction defects give rise to
great asynchrony between RV activation and LV activation.
Inter-ventricular asynchrony can range from 80 to 200 msec or
longer. In RBBB and LBBB patients, the QRS complex is widened far
beyond the normal range to between 120 msec and 250 msec as
measured on surface ECG. This increased width demonstrates the lack
of synchrony of the right and left ventricular depolarizations and
contractions.
[0141] FIG. 2 also depicts an implanted, multi-channel cardiac
pacemaker, ICD, IPG or other IMD of the above noted types for
restoring AV synchronous contractions of the atrial and ventricular
chambers and simultaneous or sequential pacing of the right and
left ventricles. The pacemaker IPG 14 is implanted subcutaneously
in a patient's body between the skin and the ribs. Three
endocardial leads 16, 32 and 52 connect the IPG 14 with the RA, the
RV and the LV, respectively. Each lead has at least one electrical
conductor and pace/sense electrode, and a remote indifferent can
electrode 20 is formed as part of the outer surface of the housing
of the IPG 14. As described further below, the pace/sense
electrodes and the remote indifferent can electrode 20 (IND _CAN
electrode) can be selectively employed to provide a number of
unipolar and bipolar pace/sense electrode combinations for pacing
and sensing functions. The depicted positions in or about the right
and left heart chambers are also merely exemplary. Moreover other
leads and pace/sense electrodes may be used instead of the depicted
leads and pace/sense electrodes that are adapted to be placed at
electrode sites on or in or relative to the RA, LA, RV and LV.
[0142] The depicted bipolar endocardial RA lead 16 is passed
through a vein into the RA chamber of the heart 10, and the distal
end of the RA lead 16 is attached to the RA wall by an attachment
mechanism 17. The bipolar endocardial RA lead 16 is formed with an
in-line connector 13 fitting into a bipolar bore of IPG connector
block 12 that is coupled to a pair of electrically insulated
conductors within lead body 15 and connected with distal tip RA
pace/sense electrode 19 and proximal ring RA pace/sense electrode
21. Delivery of atrial pace pulses and sensing of atrial sense
events is effected between the distal tip RA pace/sense electrode
19 and proximal ring RA pace/sense electrode 21, wherein the
proximal ring RA pace/sense electrode 21 functions as an
indifferent electrode (IND_RA). Alternatively, a unipolar
endocardial RA lead could be substituted for the depicted bipolar
endocardial RA lead 16 and be employed with the IND_CAN electrode
20. Or, one of the distal tip RA pace/sense electrode 19 and
proximal ring RA pace/sense electrode 21 can be employed with the
IND_CAN electrode 20 for unipolar pacing and/or sensing.
[0143] Bipolar, endocardial RV lead 32 is passed through the vein
and the RA chamber of the heart 10 and into the RV where its distal
ring and tip RV pace/sense electrodes 38 and 40 are fixed in place
in the apex by a conventional distal attachment mechanism 41. The
RV lead 32 is formed with an in-line connector 34 fitting into a
bipolar bore of IPG connector block 12 that is coupled to a pair of
electrically insulated conductors within lead body 36 and connected
with distal tip RV pace/sense electrode 40 and proximal ring RV
pace/sense electrode 38, wherein the proximal ring RV pace/sense
electrode 38 functions as an indifferent electrode (IND_RV).
Alternatively, a unipolar endocardial RV lead could be substituted
for the depicted bipolar endocardial RV lead 32 and be employed
with the IND_CAN electrode 20. Or, one of the distal tip RV
pace/sense electrode 40 and proximal ring RV pace/sense electrode
38 can be employed with the IND_CAN electrode 20 for unipolar
pacing and/or sensing.
[0144] In this illustrated embodiment, a unipolar, endocardial LV
CS lead 52 is passed through a vein and the RA chamber of the heart
10, into the CS and then inferiority in a branching vessel of the
great vein 48 to extend the distal LV CS pace/sense electrode 50
alongside the LV chamber. The distal end of such LV CS leads is
advanced through the superior vena cava, the right atrium, the
ostium of the coronary sinus, the coronary sinus, and into a
coronary vein descending from the coronary sinus, such as the great
vein. Typically, LV CS leads and LA CS leads do not employ any
fixation mechanism and instead rely on the close confinement within
these vessels to maintain the pace/sense electrode or electrodes at
a desired site. The LV CS lead 52 is formed with a small diameter
single conductor lead body 56 coupled at the proximal end connector
54 fitting into a bore of IPG connector block 12. A small diameter
unipolar lead body 56 is selected in order to lodge the distal LV
CS pace/sense electrode 50 deeply in a vein branching inferiority
from the great vein 48.
[0145] Preferably, the distal, LV CS active pace/sense electrode 50
is paired with the proximal ring RV indifferent pace/sense
electrode 38 for delivering LV pace pulses across the bulk of the
left ventricle and the intraventricular septum. The distal LV CS
active pace/sense electrode 50 is also preferably paired with the
distal tip RV active pace/sense electrode 40 for sensing across the
RV and LV as described further below.
[0146] Moreover, in a four-chamber embodiment, LV CS lead 52 could
bear a proximal LA CS pace/sense electrode positioned along the
lead body to lie in the larger diameter coronary sinus CS adjacent
the LA. In that case, the lead body 56 would encase two
electrically insulated lead conductors extending proximally from
the more proximal LA CS pace/sense electrode(s) and terminating in
a bipolar connector 54. The LV CS lead body would be smaller
between the proximal LA CS electrode and the distal LV CS active
pace/sense electrode 50. In that case, pacing of the RA would be
accomplished along the pacing vector between the active proximal LA
CS active electrode and the proximal ring RA indifferent pace/sense
electrode 21.
[0147] Typically, in pacing/defibrillation systems of the type
illustrated in FIG. 2, the electrodes designated above as
"pace/sense" electrodes are used for both pacing and sensing
functions. In accordance with one aspect of the present invention,
these "pace/sense" electrodes can be selected to be used
exclusively as pace or sense electrodes or to be used in common as
pace/sense electrodes in programmed combinations for sensing
cardiac signals and delivering pace pulses along pacing and sensing
vectors. Separate or shared indifferent pace and sense electrodes
can also be designated in pacing and sensing functions. For
convenience, the following description separately designates pace
and sense electrode pairs where a distinction is appropriate. With
respect to the present invention, a subcutaneous electrode 45
coupled to medical electrical lead 43 may be added to or
substituted for one or more of the leads or electrodes depicted in
FIG. 2. If a subcutaneous electrode 45 is utilized, a suitable
defibrillation coil 47 may be coupled to appropriate high voltage
circuitry to deliver a timed defibrillation pulse. While coil
electrode 53 is depicted coupled to a portion of RV lead 32, such
an electrode may be coupled to other portions of any of the leads
depicted in FIG. 2, such as LV electrode 57. The coil electrode 53,
subcutaneous electrode 45 or other types of suitable electrode
configurations may be electrically coupled to low voltage
pacing/sensing circuitry in addition to high voltage circuitry. As
is known, such electrodes may be disposed in a variety of locations
in, around and on the heart.
[0148] Also depicted in FIG. 2 is an RV sensor 55 and an LV sensor
59 which may comprise one or more of a variety of sensors as is
known in the art. Preferably RV sensor 55 comprises an absolute
pressure sensor, but other pressure sensors may be utilized. In
addition, RV sensor 55 may comprise an accelerometer, an impedance
electrode, a saturated oxygen sensor, a pH sensor, and the like. In
addition, each of the leads could carry a mechanical sensor for
developing systolic and diastolic pressures and a series of spaced
apart impedance sensing leads for developing volumetric
measurements of the expansion and contraction of the RA, LA, RV and
LV.
[0149] Of course, such sensors must be rendered biocompatible and
reliable for long-term use. With respect to embodiments of the
invention delivering NES therapy, the preferred location for at
least one electrode is in the coronary venous system in close
proximity to adjacent sympathetic nerves. In addition, one or more
sensors may be disposed in or on the housing 20 of IMD 14 such as
sensor 11 depicted in FIG. 2.
[0150] FIG. 3A depicts a system architecture of an exemplary
multi-chamber monitor/sensor 100 implanted into a patient's body 10
that provides delivery of a therapy and/or physiologic input signal
processing. The typical multi-chamber monitor/sensor 100 has a
system architecture that is constructed about a microcomputer-based
control and timing system 102 that varies in sophistication and
complexity depending upon the type and functional features
incorporated therein. The functions of microcomputer-based
multi-chamber monitor/sensor control and timing system 102 are
controlled by firmware and programmed software algorithms stored in
RAM and ROM including PROM and EEPROM and are carried out using a
CPU, ALU, etc., of a typical microprocessor core architecture. Of
course, such firmware and software may be modified in situ (e.g.,
in vivo) and the operational characteristics may be adapted for a
particular situation or patient. A physician or clinician may
change or more parameter which will cause a change in the detection
or response of such algorithms. Oftentimes, discrete values may be
changed such that a desired software routine is advantageously
altered, although sometimes an entirely new set of operating
software may be substituted for an existing set of operating
software, as is known in the art. The microcomputer-based
multi-chamber monitor/sensor control and timing system 102 may also
include a watchdog circuit, a DMA controller, a block mover/reader,
a CRC calculator, and other specific logic circuitry coupled
together by on-chip data bus, address bus, power, clock, and
control signal lines in paths or trees in a manner well known in
the art. It will also be understood that control and timing of
multi-chamber monitor/sensor 100 can be accomplished with dedicated
circuit hardware or state machine logic rather than a programmed
micro-computer.
[0151] The multi-chamber monitor/sensor 100 also typically includes
patient interface circuitry 104 for receiving signals from sensors
and pace/sense electrodes located at specific sites of the
patient's heart chambers and/or delivering RPS stimulation to
derive heart failure parameters or a pacing therapy to the heart
chambers. The patient interface circuitry 104 therefore comprises a
RPS stimulation delivery system 106 optionally including pacing and
other stimulation therapies and a physiologic input signal
processing circuit 108 for processing the blood pressure and
volumetric signals output by sensors. For purposes of illustration
of the possible uses of the invention, a set of lead connections
are depicted for making electrical connections between the therapy
delivery system 106 and the input signal processing circuit 108 and
sets of pace/sense electrodes located in operative relation to the
RA, LA, RV and LV.
[0152] As depicted in FIG. 3A, chemical/metabolic sensor input
and/or mechanical sensor inputs are provided to the input signal
processing circuit 108. As described with respect to FIG. 2, a wide
variety of such sensors may be utilized when practicing the present
invention.
[0153] A battery provides a source of electrical energy to power
the multi-chamber monitor/sensor operating system including the
circuitry of multi-chamber monitor/sensor 100 and to power any
electromechanical devices, e.g., valves, pumps, etc. of a substance
delivery multi-chamber monitor/sensor, or to provide electrical
stimulation energy of an ICD shock generator, cardiac pacing pulse
generator, or other electrical stimulation generator. The typical
energy source is a high energy density, low voltage battery 136
coupled with a power supply/POR circuit 126 having power-on-reset
(POR) capability. The power supply/POR circuit 126 provides one or
more low voltage power Vlo, the POR signal, one or more VREF
sources, current sources, an elective replacement indicator (ERI)
signal, and, in the case of an ICD, high voltage power Vhi to the
therapy delivery system 106.
[0154] In order for the exemplary circuit of FIG. 3A to implement
NES or cardiac defibrillation therapy according to the present
invention, the therapy delivery system 106 needs to utilize
appropriate NES and high voltage circuitry, respectively. If an NES
therapy delivery electrode is disposed remotely from the heart the
delivery of NES therapy may occur independent of the cardiac cycle
(e.g., periodically approximately between 10 ms and about ten
seconds). While many different types of pulses may be employed for
NES therapy, one or more pulses of about 0.1 to about 10 ms
duration have been shown to provide the desired results. Effective
NES therapy may be delivered using a variety of electrode
configuration (e.g., between one and several discrete electrodes).
Also, standard tip, ring, coil, can, and subcutaneous electrodes
may be utilized to effectively deliver NES therapy. While not
specifically depicted in the drawings, suitable external circuitry
may be adapted for NES therapy delivery including use of surface
electrode patches, pads or paddles as well as pericardial
electrodes. In particular, one or more electrodes disposed in the
pericardial sac will be well positioned to stimulate the
sympathetic nerves.
[0155] Virtually all current electronic multi-chamber
monitor/sensor circuitry employs clocked CMOS digital logic ICs
that require a clock signal CLK provided by a piezoelectric crystal
132 and system clock 122 coupled thereto as well as discrete
components, e.g., inductors, capacitors, transformers, high voltage
protection diodes, and the like that are mounted with the ICs to
one or more substrate or printed circuit board. In FIG. 3A, each
CLK signal generated by system clock 122 is routed to all
applicable clocked logic via a clock tree. The system clock 122
provides one or more fixed frequency CLK signal that is independent
of the battery voltage over an operating battery voltage range for
system timing and control functions and in formatting uplink
telemetry signal transmissions in the telemetry I/O circuit
124.
[0156] The RAM registers may be used for storing data compiled from
sensed cardiac activity and/or relating to device operating history
or sensed physiologic parameters for uplink telemetry transmission
on receipt of a retrieval or interrogation instruction via a
downlink telemetry transmission. The criteria for triggering data
storage can also be programmed in via downlink telemetry
transmitted instructions and parameter values The data storage is
either triggered on a periodic basis or by detection logic within
the physiologic input signal processing circuit 108 upon
satisfaction of certain programmed-in event detection criteria. In
some cases, the multi-chamber monitor/sensor 100 includes a
magnetic field sensitive switch 130 that closes in response to a
magnetic field, and the closure causes a magnetic switch circuit to
issue a switch closed (SC) signal to control and timing system 102
which responds in a magnet mode. For example, the patient may be
provided with a magnet 116 that can be applied over the
subcutaneously implanted multi-chamber monitor/sensor 100 to close
switch 130 and prompt the control and timing system to deliver a
therapy and/or store physiologic episode data when the patient
experiences certain symptoms. In either case, event related data,
e.g., the date and time, may be stored along with the stored
periodically collected or patient initiated physiologic data for
uplink telemetry in a later interrogation session.
[0157] In the multi-chamber monitor/sensor 100, uplink and downlink
telemetry capabilities are provided to enable communication with
either a remotely located external medical device or a more
proximal medical device on the patient's body or another
multi-chamber monitor/sensor in the patient's body as described
above with respect to FIG. 2 and FIG. 3A (and FIG. 3B described
below). The stored physiologic data of the types described above as
well as real-time generated physiologic data and non-physiologic
data can be transmitted by uplink RF telemetry from the
multi-chamber monitor/sensor 100 to the external programmer or
other remote medical device 26 in response to a downlink
telemetered interrogation command. The real-time physiologic data
typically includes real time sampled signal levels, e.g.,
intracardiac electrocardiogram amplitude values, and sensor output
signals. The non-physiologic patient data includes currently
programmed device operating modes and parameter values, battery
condition, device ID, patient ID, implantation dates, device
programming history, real time event markers, and the like. In the
context of implantable pacemakers and ids, such patient data
includes programmed sense amplifier sensitivity, pacing or
cardioversion pulse amplitude, energy, and pulse width, pacing or
cardioversion lead impedance, and accumulated statistics related to
device performance, e.g., data related to detected arrhythmia
episodes and applied therapies. The multi-chamber monitor/sensor
thus develops a variety of such real-time or stored, physiologic or
non-physiologic, data, and such developed data is collectively
referred to herein as "patient data."
[0158] The physiologic input signal processing circuit 108
therefore includes at least one electrical signal amplifier circuit
for amplifying, processing and in some cases detecting sense events
from characteristics of the electrical sense signal or sensor
output signal. The physiologic input signal processing circuit 108
in multi-chamber monitor/sensors providing dual chamber or
multi-site or multi-chamber monitoring and/or pacing functions
includes a plurality of cardiac signal sense channels for sensing
and processing cardiac signals from sense electrodes located in
relation to a heart chamber. Each such channel typically includes a
sense amplifier circuit for detecting specific cardiac events and
an EGM amplifier circuit for providing an EGM signal to the control
and timing system 102 for sampling, digitizing and storing or
transmitting in an uplink transmission. Atrial and ventricular
sense amplifiers include signal processing stages for detecting the
occurrence of a P-wave or R-wave, respectively and providing an
ASENSE or VSENSE event signal to the control and timing system 102.
Timing and control system 102 responds in accordance with its
particular operating system to deliver or modify a pacing therapy,
if appropriate, or to accumulate data for uplink telemetry
transmission or to provide a Marker Channel.RTM. signal in a
variety of ways known in the art.
[0159] In addition, the input signal processing circuit 108
includes at least one physiologic sensor signal processing channel
for sensing and processing a sensor derived signal from a
physiologic sensor located in relation to a heart chamber or
elsewhere in the body.
[0160] Now turning to FIG. 3B, another system architecture for use
in conjunction with the present invention is depicted. FIG. 3B is
an exemplary system that may be utilized to deliver therapy by
incorporating the system and method described above. Notably, the
depicted system includes a sense amplifier 534 to sense electrical
signals such as EGM signals using one or more leads placed within a
respective chamber of the heart. These signals are used to
determine atrial and ventricular depolarizations and Q-T length so
that NES and RPS delivery is provided in a safe manner. One or more
physiological or hemodynamic signals may be sensed using sensors
such as those discussed above. These additional signals, which are
shown collectively provided on line 505, may be used to determine
cardiac output so that therapy may be initiated, terminated, and/or
optimized.
[0161] The system of FIG. 3B further includes a timer/controller to
control the delivery of pacing pulses on output lines 500 and 502.
This circuit, alone or in conjunction with microprocessor 524,
controls interval lengths, pulse amplitudes, pulse lengths, and
other waveform attributes associated with the NES and RPS pulses.
Output circuit 548 delivers high-voltage stimulation such as
defibrillation shocks under the control of defibrillation control
circuit 554.
[0162] Not all of the conventional interconnections of these
voltages and signals are shown in either FIG. 3A or FIG. 3B and
many other variations on the illustrated electronic circuitry are
possible, as is known to those of skill in the art.
[0163] FIG. 4 schematically illustrates one pacing, sensing and
parameter measuring channel in relation to one heart chamber. A
pair of pace/sense electrodes 140, 142, a sensor 160 (e.g., a
pressure, saturated oxygen, flow, pH or the like), and a plurality,
/e.g., four, impedance measuring electrodes 170, 172, 174, 176 are
located in operative relation to the heart chamber. The pair of
pace/sense electrodes 140, 142 are located in operative relation to
the heart chamber and coupled through lead conductors 144 and 146,
respectively, to the inputs of a sense amplifier 148 located within
the input signal processing circuit 108. The sense amplifier 148 is
selectively enabled by the presence of a sense enable signal that
is provided by control and timing system 102. The sense amplifier
148 is enabled during prescribed times when pacing is either
enabled or not enabled as described below in reference to the
measurement of the parameters of heart failure. The blanking signal
is provided by control and timing system 102 upon delivery of a
pacing or RPS pulse or pulse train to disconnect the sense
amplifier inputs from the lead conductors 144 and 146 for a short
blanking period in a manner well known in the art. When sense
amplifier 148 is enabled and is not blanked, it senses the
electrical signals of the heart, referred to as the EGM, in the
heart chamber. The sense amplifier provides a sense event signal
signifying the contraction of the heart chamber commencing a heart
cycle based upon characteristics of the EGM, typically the P-wave
when the heart chamber is the RA or LA and the R-wave, when the
heart chamber is the RV or LV, in a manner well known in the pacing
art. The control and timing system responds to non-refractory sense
events by restarting an escape interval (El) timer timing out the
El for the heart chamber, in a manner well known in the pacing
art.
[0164] The pair of pace/sense electrodes 140, 142 are also coupled
through lead conductors 144 and 146, respectively, to the output of
a pulse generator 150. The pulse generator 150, within RPS/pacing
delivery system 106, selectively provides a pacing pulse to
electrodes 140, 142 in response to a RPS/PACE trigger signal
generated at the time-out of the El timer within control and timing
system 102 in a manner well known in the pacing art. Or, the pulse
generator 150 selectively provides a RPS pulse or pulse train to
electrodes 140, 142 in response to a RPS/PACE trigger signal
generated at the time-out of an ESI timer within control and timing
system 102 in the manner described in the above-referenced '098
patent to cause the heart chamber to contract more forcefully, the
increased force depending upon the duration of the ESI.
[0165] The sensor 160 and/or other physiologic sensor is coupled to
a sensor power supply and signal processor 162 within the input
signal processing circuit 108 through a set of lead conductors 164
that convey power to the sensor 160 and sampled blood pressure P
signals from the sensor 160 to the sensor power supply and signal
processor 162. The sensor power supply and signal processor 162
samples the blood pressure impinging upon a transducer surface of
the sensor 160 located within the heart chamber when enabled by a
sense enable signal from the control and timing system 102. As an
example, absolute pressure P, developed pressure DP and pressure
rate of change dP/dt sample values can be developed by sensor power
supply and signal processor unit 162 or by the control and timing
system 102 for storage and processing as described further below.
The sensor 160 and a sensor power supply and signal processor 162
may take the form disclosed in commonly assigned U.S. Pat. No.
5,564,434.
[0166] The set of impedance electrodes 170, 172, 174 and 176 is
coupled by a set of conductors 178 and is formed as a lead of the
type described in the above-referenced '717 patent that is coupled
to the impedance power supply and signal processor 180.
Impedance-based measurements of cardiac parameters such as stroke
volume are known in the art as described in the above-referenced
'417 patent which discloses an impedance lead having plural pairs
of spaced surface electrodes located within the heart chamber. The
spaced apart electrodes can also be disposed along impedance leads
lodged in cardiac vessels, e.g., the coronary sinus and great vein
or attached to the epicardium around the heart chamber. The
impedance lead may be combined with the pace/sense and/or pressure
sensor bearing lead.
[0167] A measure of heart chamber volume V is provided by the set
of impedance electrodes 170, 172, 174 and 176 when the impedance
power supply and signal processor 180 is enabled by an impedance
measure enable signal provided by control and timing system 102. A
fixed current carrier signal is applied between the pairs of
impedance electrodes and the voltage of the signal is modulated by
the impedance through the blood and heart muscle which varies as
distance between the impedance electrodes varies. Thus, the
calculation of the heart chamber volume V signals from impedance
measurements between selected pairs of impedance electrodes 170,
172, 174 and 176 occurs during the contraction and relaxation of
the heart chamber that moves the spaced apart electrode pairs
closer together and farther apart, respectively, due to the heart
wall movement or the tidal flow of blood out of and then into the
heart chamber. Raw signals are demodulated, digitized, and
processed to obtain an extrapolated impedance value. When this
value is divided into the product of blood resistivity times the
square of the distance between the pairs of spaced electrodes, the
result is a measure of instantaneous heart chamber volume V within
the heart chamber.
[0168] In accordance with the present invention, the IMD measures a
group of parameters indicative of the state of heart failure
employing EGM signals, measures of absolute blood pressure P and/or
dP/dt, saturated oxygen, flow, pH or the like and measures of heart
chamber volume V over one or more cardiac cycles.
[0169] The steps of deriving the RF, MR, E.sub.ES, and tau
parameters indicative of the state of heart failure are more fully
described in the '631 disclosure and will not be repeated here. For
the uninitiated the following description is provided; however, if
additional details are desired the reader is directed to the '631
disclosure. These parameters are determined periodically throughout
each day regardless of patient posture and activity. However, the
patient may be advised by the physician to undertake certain
activities or movements at precise times of day or to
simultaneously initiate the determination of the parameters though
use of a magnet or a remote system programmer unit (not depicted)
that is detected by the IMD. Certain of the parameters are only
measured or certain of the parameter data are only stored when the
patient heart rate is within a normal sinus range between
programmed lower and upper heart rates and the heart rhythm is
relatively stable. The parameter data and related data, e.g., heart
rate and patient activity level, are date and time stamped and
stored in IMD memory for retrieval employing conventional telemetry
systems. Incremental changes in the stored data over time provide a
measure of the degree of change in the heart failure condition of
the heart. Such parameter data and related data may be read,
reviewed, analyzed and the like and the parameter data may be
changed based on a current patient condition, a patient history,
patient or physician preference(s) and the like.
[0170] Turning to FIG. 5, the timing diagram illustrates the timing
of delivery of stimulation to a heart chamber in relation to a
timed interval from a sensed or paced event as well as alternative
pulse waveforms of the RPS/NES stimulation. In accordance with one
aspect of the present invention, a therapeutic stimulation delay
illustrated in tracing (e) is timed out from a sensed or paced
event (e.g., the illustrated V-EVENTs) that for NES is shorter than
the refractory period of the heart persisting from the sensed or
paced event. A stimulus pulse train is delivered to the atria
and/or ventricles in the depicted therapy delivery interval of
tracing (f) commencing after time-out of the delay so that for NES
therapy delivery at least the initial pulse(s) of the pulse train
fall within the end portion of the refractory period. The pulses
for RPS therapy delivery is intended to be supra-threshold in
nature, that is, of sufficient energy to depolarize the heart when
they are delivered in the non-refractory period of the heart cycle
so that the heart is captured by at least one of the RPS pulses
falling outside the refractory period. The initial pulses delivered
during the refractory period can also potentiate the heart. For
simplicity of illustration, the tracings (f)-(j) are expanded in
length, and the depolarization of the heart that they cause is not
depicted in tracing (a). The amplitude and number of refractory
interval pulses and RPS pulses in each therapy pulse train and the
spacing between the pulses may also differ from the illustrated
tracings (g)-(j).
[0171] The ventricular sense or pace event detected in tracing (b)
also triggers the timing out of an escape interval in tracing (c)
which may be terminated by the sensing of a subsequent atrial or
ventricular event, depending on the operating mode of the system.
The first depicted sequence in FIG. 5 shows the full time-out of
the escape interval in tracing (c), the refractory period in
tracing (d), and the therapy delay and delivery intervals in
tracings (e) and (f). The therapy delay and therapy delivery
intervals can be derived as a function of an intrinsic V-V or V-A
escape interval derived by measuring and averaging intervals
between intrinsic ventricular and/or atrial sense events or paced
events. The therapy delay can also be determined from a measurement
of the Q-T interval. As illustrated, the therapy delay in tracing
(e) delays delivery of the therapy pulse train until the QRS
complex ends or about 40-60 ms after the V-EVENT well before the
start of the vulnerable period of the heart which occurs near the
end of the T-wave. The therapy delivery interval is timed to
time-out well before the end of the previously derived V-V or V-A
escape interval, but is extended for ease of illustration of the
pulse trains in tracings (f)-(j).
[0172] The therapy stimulation energy is delivered in the form of a
burst of X constant or variable energy stimulation pulses separated
by a pulse separation interval between each pulse of the burst. All
of the pulses can have the same amplitude and energy as shown in
waveform 3 of tracing (i). Or the leading and/or trailing pulses of
the pulse train can have ramped amplitudes similar to the waveforms
1 and 2 illustrated in tracings (g) and (h). In tracings (g) and
(h), the ramp up leading edge amplitudes of a sub-set of the pulses
of the burst are shown increasing from an initial amplitude to a
maximum amplitude. In tracing (g), the ramp down trailing edge
amplitudes of a further sub-set of the pulses of the burst are
shown decreasing from the maximum amplitude to a terminating
amplitude.
[0173] Alternatively, the initial set of pulses delivered during
the refractory period can have a higher pulse amplitude or width as
shown by waveform 4 illustrated in tracing (j). The high energy
pulses delivered during the refractory period can enhance
potentiation during subsequent heart cycles. Tracing (j) also
illustrates alternative numbers and spacing of the pulses of the
pulse train, and it will be understood that this embodiment can
also employ the number of pulses and pulse spacing of waveforms
1-3.
[0174] In addition, it may be desirable to avoid delivering any
therapy pulses in the vulnerable period of the heart near the end
of the T-wave, particularly if high energy pulses are delivered
during the refractory period. Tracing (j) also illustrates a
vulnerable period delay between the high energy pulses delivered
during the refractory period and the lower energy RPS pulses to
avoid delivering any pulses during the vulnerable period of the
heart. It would also be possible to lower the pulse energy of the
pulses delivered later in the refractory period.
[0175] The therapy delivery capability is preferably implemented
into a system that may include conventional pacing therapies and
operating modes as well as cardioversion/defibrillation
capabilities or as a stand alone system for simply providing pulse
therapies to effect potentiation of myocardial cells between sensed
PQRST complexes shown in FIG. 5.
[0176] Detailed Description of Atrial Coordinated Pacing per the
Invention.
[0177] FIG. 6 illustrates untreated chronic HF dysfunction with a
rapid sinus rhythm (100 bpm) in an ambulatory model of chronic HF.
In FIG. 6, regular atrial and ventricular electrograms (AEGM and
VEGM) are illustrated, and a measurement of an index of contractile
function (LV dP/dtmax) is shown which is derived from LV pressure
(LVP). In FIG. 6 the valued of LV dP/dtmax is shown to be about 900
mmHg/s.
[0178] FIG. 7 illustrates HF dysfunction treated with RPS therapy
and atrial coordinated pacing (ACP) according to the present
invention. In FIG. 7, the subject with chronic HF is continuously
treated with ventricular RPS therapy (channel marked Vtherapy) and
atrial coordinated pacing ACP (channel marked ACP). The result is a
stable rhythm at a lower rate (around 50 bpm) with sustained
contractile enhancement (LV dP/dtmax is improved to about 1800
mmHg/s). It can be seen that occasionally, when the intrinsic
atrial rate drops, an atrial pace event occurs to initiate a
cardiac cycle (see Apace event aligned with the vertical line
labeled "AAI rate support" (at the right of FIG. 7). One result of
RPS therapy and ACP therapy is a slower rhythm with enhanced
mechanical function occurring on the portion of the cardiac cycle
with intrinsic AV conduction and natural ventricular
depolarization. This therapy regimen causes a forced deceleration
of the cardiac rhythm. This type of stimulation therapy also
appears suitable for HF patients having intact AV conduction that
suffer from SVT (supraventricular tachyarrhythmia) as will be
further described and illustrated with respect to FIG. 36
(below).
[0179] Referring now to FIG. 8, rhythm irregularities are depicted
during RPS therapy (without ACP). In the left portion of FIG. 8, HF
dysfunction is treated with RPS therapy and a form of ACP
consisting of AAI pacing at 120 bpm with 2:1 AV block. In the right
portion of FIG. 8, HF dysfunction is treated with RPS therapy
without AAI pacing. Although it can be appreciated that
contractility remains improved (about 1900 mmHg/s), variations in
refractoriness and intrinsic intervals commonly result in
intermittent 1:1 and 2:1 AV conduction (seen at right of FIG. 8).
The heart tissue is not guaranteed sufficient time in diastole for
good filling, coronary flow, and ion flux stabilization. As a
result, the peripheral pulse rate is variable, mechanical
enhancement is less consistent, and the heart more prone to
arrhythmias and metabolic intolerance.
[0180] FIG. 9A-9D is a schematic of atrial coordinated pacing (ACP)
from the perspective of an implantable medical device, such as an
ICD or pacemaker. In FIG. 9A, a normal sinus rhythm is depicted in
which each atrial instrinsic depolarization (denoted As for atrial
sense event) conducts to the ventricles and produces an intrinsicly
conducted ventricular depolarization (labeled Vs for ventricular
sense event). If the intrinsic atrial rate is too low, atrial
pacing (denoted Ap) may substitute for atrial sense events shown.
With respect to FIG. 9B, introduction of ventricular stimulation
therapy pulses (either RPS alone or combined RPS and NES- denoted
Vth) occurs and the ventricles become refractory a second time. As
a result, a 2:1 conduction pattern may arise in which every other
atrial sense event is blocked. This pattern is often unstable (see
FIG. 8 above) and may result in effective ventricular rates that
are too slow (brady) or too fast (tachy).
[0181] With respect to FIG. 9C, which depicts a simple form of ACP,
the atria are paced at a rate faster than the intrinsic rate and
the 2:1 block is regularized. This approach helps when the result
of the case depicted in FIG. 9B was an effective ventricular rate
that was too slow or too irregular, but does not allow the
subject's physiology to set heart rate, paces the atrium
frequently, and may result in an excessive heart rate.
[0182] With respect to FIG. 9D, which depicts a preferred
implementation of ACP, the atria are paced for the purpose of
coordination (denoted "Acp") after the ventricular sense event and
around the same time as the Vth pulse or pulses. The ACP pace
events do not conduct to the ventricles but reset the sinus node.
Thus, the next atrial sense event occurs at a time governed by
physiologic demand. The resulting "potentiated" beats are thus
advantageously preceeded by adequate filling time, better coronary
flow, and more time for myocye ion fluxes to normalize.
[0183] Of course, as is well known in the art, atrial pacing may be
employed if the intrinsic atrial rate drops too low (see FIG.
7--above) and maintain the advantages discussed. Furthermore, if AV
or ventricular conduction is impaired, ventricular pacing at an
appropriate AV interval may also be employed. This may take the
form of single or multiple site (e.g. biventricular) pacing.
[0184] For TCP or transthoracic pacing such as employed with an
AED, although atrial sensing is not readily available (nor is
atrial pacing) ACP as illustrated by FIG. 9D can still be
performed. To practice such ACP, a TCP therapy pulse triggered from
a sensed R-wave (or pacing pulse) would induce depolarization in
both atria and ventricles simultaneously and achieve RPS and ACP
according to the present invention.
[0185] As is known in the art, timing and delivery of ACP pulses
are preferably under microprocessor control, such as depicted in
the system diagrams of FIG. 3A and FIG. 3B. Also, such timing
parameters are programmable and may be adjusted or modified by a
clinician.
[0186] With general reference to FIG. 6 through FIG. 9, it should
be appreciated that ventricular therapy, denoted Vth, includes RPS
and optionally nonexcitatory neurostimulation (NES). The
determinants of timing and amplitude of the Vth pulse or pulses
have been discussed previously in the '631 disclosure and elsewhere
in this invention disclosure. Intervals from the preceding Vs or Vp
event are chosen to yield the desired effects (excitatory or
nonexcitatory) and amplitude of potentiation (RPS). Furthermore,
the choice of ACP timing to implement safe and physiologic
enhancement of cardiac function is also important. If the Vth
therapy pulse is vetoed by safety rules or other reasons or does
not capture, the ACP pulse is withheld. When excitatory ventricular
therapy is discontinued, so too is ACP. If this is not done, there
results a form of pacemaker mediated tachycardia (PMT). Unless
potentiation is intended to come from conduction of the ACP pulse's
depolarization, the goal of ACP is to guarantee atrial
depolarization and AV block. These considerations result in bounds
for ACP timing that will be discussed for the case of therapy
delivered every cardiac cycle.
[0187] For example, let X represent the time from the potentiated
Vs (or Vp) to the scheduled delivery of ACP. Let Y similarly
represent the time from the potentiated Vs (or Vp) to the scheduled
delivery of Vth. These rules behind calculation of the value of Y
are described in the '631 disclosure, and in the present patent
disclosure with respect to discussion and illustrations regarding
feedback control, the safety lockout rules, and the identification
and determination of refractory interval. The value of X must be
larger (i.e., longer) than the A-A refractory period (which is
often approximately 200-300 ms). The value of X must also be chosen
such that the resulting depolarization passes the AV node or
ventricle while in a refractory state. Let R.sub.v denote the V-V
refractory period and R.sub.A denote the A-A refractory period.
Further let AV denote the AV conduction delay (that is the time
from an Apace to a Vsense event, less any delays associated with
sensing itself). Then X must satisfy the following pair of
inequalities:
X>R.sub.A and Y-V<X<Y-AV+R.sub.v
[0188] Experience has shown values of X in the range of 150 to 200
ms to satisfy both inequalities and yield the desired effects. This
generally places ACP shortly before excitatory Vth pulses. The
reader should note that ACP is subject to the same safety veto
rules as Vth (discussed in relation to safety lockout rules section
of this patent disclosure) but faces an additional challenge. That
is, if the Vth pulse amplitude(s) is sub-threshold or entirely
within the refractory period, no potentiation results. Although the
arrhythmia risk is essentially zero, the subject is deprived of the
benefit of RPS therapy. However, if ACP is delivered above
threshold in this setting, this could raise the ventricular rate by
conducting to the ventricles. The resulting Vsense initiates
another ACP and establishes a PMT with cycle length of X+AV. The
present invention therefore incorporates an additional ACP lockout
rule that ends this type of PMT after a single beat. This lockout
rule requires that if there is no atrial event (sense or pace) over
the previous cardiac cycle (from Vsense to Vsense) or in a
sufficient interval, then the ACP is selectively vetoed for the
next N cardiac cycles and evidence sought of extrasystole
capture.
[0189] Detailed Description of Non-Excitatory Neurostimulation.
[0190] Now turning to FIG. 10 in which sympathetic innervation of
the heart and electrode locations for nonexcitatory stimulation
(NES) is depicted in a partially exploded perspective view with
portions removed for ease of inspection. Significant elements in
FIG. 10 are identified as the following: spinal cord, cervical and
thoracic segmental nerves (collectively denoted by the letter "A"),
cervical and thoracic chain ganglia (up and down near the vertebral
bodies at back of thorax (denoted with the letter "B"), autonomic
nerves traveling through the thorax and mediastinum toward great
vessels and the heart 10 and including the ansa subclavia (denoted
with the letter "C"), various cardiac nerves often traveling near
coronary vessels (denoted with the letter "D"), and cardiac nerves
in the myocardium (denoted with the letter "E"). Electrodes (such
as depicted in FIG. 2) may be positioned anywhere along these
pathways to direct electrical stimulation current to these
sympathetic nerves and avoid painful stimulation of other nerves or
organs and avoid pacing the heart 10. Alternatively, subcutaneous
electrodes such as the can electrode or other subcutaneous patch
electrodes may be employed to stimulate broadly regions A-E and
reserved for severe dysfunction including cardiogenic shock and
electromechanical dissociation (EMD) or pulseless electrical
activity (PEA). Furthermore, subcutaneous patch, pad electrodes or
paddle electrodes may be similarly employed to direct electrical
current to related sympathetic neural tissue in accordance with
this aspect of the present invention.
[0191] Now turning to FIG. 11 which depicts neurostimulation and
the cardiac refractory period, it can be seen that a stimulation
threshold curve of cardiac muscle and the electrode location for
nonexcitatory neurostimulation govern stimulation pulse timing.
Adjacent to the heart where stimulation could cause capture, the
NES pulses are delivered during the refractory period and/or remain
subthreshold (i.e., below a threshold magnitude). Further from the
cardiac tissue, the stimulation pulses may have different amplitude
and may be more widely spaced.
[0192] FIG. 12 is a diagram illustrating an example of NES therapy
delivery. This diagram illustrates the effects of stimulating
sympathetic nerves near the heart with increasing amounts of
current (1, 2.5, and 5 mA, respectively). Such NES stimulation
during the refractory period results in a dose dependent increase
of aortic blood pressure (AoP), contractility (LV dP/dt), heart
rate, and cardiac output. The magnitude of the response may be
similarly controlled by adjusting the duration and/or number of
pulses in the NES pulse train. The NES therapy timing and stimulus
parameters are preferably controlled by a microprocessor or
hardware and programmable with input values determined by
algorithms or clinicians, such as depicted in the system diagrams
of FIG. 3A and FIG. 3B.
[0193] Detailed Description of Safety Lockout Rules.
[0194] FIG. 13A through 13C illustrate the consequences of RPS
stimulation during a tachycardia event. The inventors have
discovered that it is preferable, if not absolutely necessary, to
cease delivery of excitatory RPS stimulation therapy during
tachycardias. In the condition depicted in FIG. 13A, the
ventricular mechanical rate is low (60 bpm), the amplitude of the
potentiation is large, and there is sufficient time in diastole for
ventricular filling. In the condition depicted in FIG. 13B the
heart rate has effectively doubled (i.e., increased to 120 bpm),
and while the amplitude of potentiation remains large the diastolic
time is shorter. In the condition depicted in FIG. 13C, the heart
rate is even higher (i.e., at about 150 bpm) and the extrasystole
encroaches severely on the cardiac cycle's time in diastole.
Furthermore, at these high heart rates RPS potentiation diminishes.
The RPS stimulation transforms the 150 bpm tachycardia to a
ventricular tachycardia with mechanical alternans and an effective
rate of 300 bpm. Heart rates this high are poorly tolerated and
will further contribute to cardiac dysfunction, heart failure
decompensation, and predispose a person subjected to such an
effective heart rate to VT or VF.
[0195] Referring now to FIG. 14, a flow chart for a safety lockout
rule for application of excitatory RPS stimulation is depicted. It
can be appreciated that each new cardiac cycle begins with a
ventricular event (Vevent) that is either a Vpace or Vsense. The
safety lockout rule has veto power over the decision to deliver
excitatory RPS stimulation to the ventricle and possibly atrial
coordinated pacing (ACP) during this cycle. If the prior V-V
interval is greater than a threshold value, RPS and/or ACP pulses
are enabled for this cycle. Should the V-V interval be too short,
stimulation therapy is aborted. This prevents stimulation therapy
from further adding to the arrhythmic potential of an intrinsic
premature ventricular contraction (PVC). Stimulation with a short
coupling interval, particularly if immediately following other
short intervals is significantly pro-arrhythmic and is, of course,
to be avoided. The safety lockout rule also prevents application of
excitatory therapy during various tachycardias including sinus
tachycardia, supraventricular tachycardia (SVT), ventricular
tachycardia (VT), or ventricular fibrillation (VF). The threshold
used may either be a fixed value or derived from other hemodynamic
or electrogram based parameters and is typically 400-600 ms. The
safety lockout rules may operate using a variety of timing schemes
which are microprocessor or hardware controlled and programmable
with input values determined by algorithms or clinicians, such as
depicted in the system diagrams of FIG. 3A and FIG. 3B.
[0196] Detailed Description of Start-Stop Rules.
[0197] Referring now to FIG. 15, which is a top level flow chart
governing initiation and termination of stimulation therapies
according to the present invention. If therapy is not currently
enabled, therapy can be initiated by a clinician, the patient, or
the device. The clinician is able to preempt an assessment by the
device or patient to begin stimulation therapy based on
consultation with the patient, signs or symptoms of cardiac
dysfunction, or lab results. If begun in this manner the therapy
may have a duration and termination criteria different from patient
or device initiated therapy. Similarly, the patient, as a result of
symptoms or anticipated exertion may preempt the device and begin
therapy. Finally, the device may automatically begin therapy based
on preprogrammed time of day or due to sensor signals, including
electograms, hemodynamic, activity sensor signals, and other
physiologic sensor signals. Therapy may be discontinued by
clinician command, patient request, or device based criteria that
include sufficient therapy duration and sensor assessment of
sufficient benefits or risks.
[0198] In FIG. 16, which is a more detailed flow chart of automated
sensor-governed initiation of stimulation therapies. Based on
electrogram (EGM) sensor signals derived from a patient (both
presently and recently), the device first looks for and treats
cardiac rhythm problems before moving on to examine other sensor
signal data. If the cardiac rhythm appears satisfactory, then
hemodynamic sensors such as pressure and flow are employed. If
there is sufficient dysfunction and duration, therapy begins.
Metabolic or other physiologic sensor severity and duration
assessments as well as a prescheduled time of day criteria may also
initiate stimulation therapies according to the present
invention.
[0199] With respect to FIG. 17, which is an expanded diagram of
suspension or termination of stimulation therapies according to the
present invention. If a tachyarrhythmia develops of sufficient rate
or duration (e.g., which exceeds a predetermined rate or duration
threshold), the therapy is either temporarily suspended or halted
altogether and the arrhythmia treated by any of a variety of
well-known means such as antitachycardia pacing (ATP),
cardioversion, or the like. Upon restoration of a more normal
rhythm, the device may or may not re-enable automatic therapy
delivery. The device may also readjust its stimulation therapy
parameters such as timing and amplitude to achieve a lower
arrhythmia risk profile, trading physiologic benefit for arrhythmia
risk (on the presumption that the stimulation therapies either
caused or predisposed the subject to this arrhythmia). If the
rhythm remains satisfactory, the device checks if either duration
or combined hemodynamic improvement and duration criteria are met.
If so, the therapies are again either temporarily suspended or
halted altogether. Automated therapies may be re-enabled after a
period of time or left disabled. In order to prevent multiple brief
cyclic applications of therapy, the improvement criteria may be
different from the initiation criteria to implement a
hysteresis-like effect. Therapies may also be disabled upon
reaching a fixed number of therapy applications and require an
external override to restart.
[0200] Referring now to FIG. 18, which depicts termination of a
tachyarrhythmia and initiation of therapy for cardiac dysfunction,
FIG. 18 illustrates some the therapy initiation rules described
above. As can be seen with reference to FIG. 18, a tachyarrhythmia
is ended at about 17:46:05 and electrogram sensors (here the
surface electrocardiogram (ECG) confirm the existence of a
reasonable rhythm and rate. However, hemodynamic sensors such as
arterial blood pressure (ABP) and left ventricular pressure (LVP)
confirm a severe level of dysfunction (e.g. LV dP/dtmax<400
mmHg/s) that is sustained for over 6 seconds and over 12 cardiac
cycles. As a result, the decision to initiate stimulation therapies
occurs at about 17:46:15. A prompt response of arterial blood
pressure, LVP, coronary blood flow, aortic blood flow, and LV
dP/dtmax is seen coincident with the application of RPS therapy
pulses (Vtherapy).
[0201] In FIG. 19, an initiation of and response to RPS stimulation
therapy is depicted. In other conditions such as HF, not
necessarily associated with a preceding or concurrent
tachyarrhythmia, cardiac dysfunction may deteriorate to the point
where device initiated therapy is required. The onset of such
cardiac dysfunction may either be gradual or sudden but upon
establishing sufficient severity and duration, RPS stimulation
therapy is begun. The excitatory RPS therapy shown here provides
much needed increases of arterial blood pressure (ABP), coronary
flow (CorFlow) and aortic flow (AorFlow) and the LV dp/dtmax value
more than doubles from pre-RPS therapy in approximately five
seconds.
[0202] FIG. 20 depicts termination of RPS therapy based on duration
and response criteria. In FIG. 20, the termination criteria is met
and RPS stimulation therapy is halted. In this case, stimulation
therapy consists of atrial-only RPS stimulation therapy pulses
(Ath) which capture and reset the sinus node, are conducted to the
ventricles, and produce atrial and ventricular RPS due to natural
conduction. In this sequence, the patient has maintained a good RV
pressure (RVP) and LV dP/dtmax for over 30-60 seconds, and
therefore the atrial-only RPS stimulation therapy is halted.
Although the heart rate accelerates and contractility diminishes,
cardiac function has recovered very significantly from the levels
shown in FIG. 18 and FIG. 19 (just described).
[0203] Now turning to FIG. 21 which depiction a dramatic example of
lifesaving RPS stimulation therapy. FIG. 21 illustrates (and
clearly demonstrates) that post extra-systolic potentiation
stimulation therapy can facilitate rapid recovery of cardiac
function following a long duration of paced tachyarrhythmia in an
anesthetized canine subject.
[0204] In FIG. 21, the trace denoted "ECG" is a surface ECG record,
the trace denoted "ABP" is a record of arterial blood pressure
measured via a catheter in the aorta of the subject, the trace
denoted "RVP" is a record of blood pressure measured within the
right ventricle. The trace denoted "CorFlow" is a record of blood
flow in the coronary artery, the trace denoted "LVdP/dtmax" is a
record of the maximum value of the 1.sup.st derivative of left
ventricular pressure per each cardiac cycle, and the trace denoted
"CO" is a recording of cardiac output as derived from mean aortic
flow. The record depicted in FIG. 21 begins with the final few
seconds of a six-minute long, paced tachyarrhythmia (the portion of
the traces before the "End VT" marker). This is followed by
approximately 10 seconds of normal sinus rhythm (NSR) with severe
hemodynamic dysfunction that could be classified as pulseless
electrical activity (PEA) or electro-mechanical dissociation (EMD).
During this time, coronary blood flow and cardiac output have not
visibly increased compared to flows occurring during the
tachyarrhythmia. Without adequate blood flow, the heart will remain
ischemic and the subject will likely die of PEA. The portion of
FIG. 21 denoted by a horizontal arrow marked "RPS Therapy," marks
the period during which RPS pacing therapies were delivered in the
right ventricular apex of the heart of the subject. During this
period, all measured pressures and flows are appreciably augmented
on the very first cardiac cycle following delivery of the first
pacing (RPS) stimuli. The values continue to increase and begin to
recover to normal physiologic levels within approximately one
minute. At the end of the RPS therapy delivery segment, there has
been sufficient coronary flow to re-perfuse the heart, allowing it
to resume function without additional therapy. It cannot be
overemphasized that return of spontaneous circulation in this
subject occurred without any pharmacological or mechanical support
therapy or treatment but instead relied exclusively on electrical
stimulation delivered according to the present invention.
[0205] Recognition of the need for such therapy may depend on
clinicians or an automated device, either implanted or external,
and stimulation therapy applied transcutaneously or from electrodes
on or near the heart. FIG. 22, which is an annotated version of
FIG. 17, contains some added information regarding duration and
improvement criteria, halting therapy delivery and adjustment of
amplitude and timing of RPS therapy to lower arrhythmia risk.
[0206] The start-stop rules may operate using a variety of schemes
and sensor inputs as depicted in FIG. 2 which are microprocessor or
hardware controlled and programmable with values determined by
algorithms or clinicians, such as depicted in the system diagrams
of FIG. 3A and FIG. 3B.
[0207] Detailed Description of Identification of Refractory and
Non-Refractory Intervals.
[0208] Turning now to FIG. 23 (A through D) which is a composite
illustration composed of four X-Y plots of data showing critical
timing sequences between such plots of data with respect to
delivery of excitatory (RPS) and nonexcitatory stimulation (NES)
therapy. An unlabeled time-aligned surface representative ECG
electrogram trace appears at the top of the figures for ease of
cross-reference.
[0209] In FIG. 23A, a stimulus intensity curve is depicted wherein
a primary determinant of the timing associated with arrhythmia risk
and hemodynamic benefit derived from RPS excitatory stimulation. It
will be appreciated that stimulation pulses of greater amplitude
than the curve (at a given moment in time) are necessary to capture
and thus provide benefit from RPS stimulation therapy. An absolute
refractory period is depicted in FIG. 23A. During this period no
depolarizations result and this is ideal for nonexcitatory
neurostimulation (NES) with electrodes near the heart. In the
period labeled "vulnerable period," which occurs just outside of
the absolute refractory period, very high amplitude pulses can
cause arrhythmias including repetitive extrasystoles, VT, or VF.
For practical purposes, excitatory stimulation pulses are delivered
some margin above the threshold so that capture is a binary
phenomenon. Stimulation pulse amplitude, however, is also
maintained low so that the risk of arrhythmias is very low even
when timed to coincide with the vulnerable period (for comparison
see FIG. 23C, "arrhythmia induction risk curve"). As is well known
in the literature, the magnitude of the potentiation seen on the
beat following the extrasystole (the post extrasystole beat) is a
function of the extrasystole's timing--becoming greatest just
before losing capture (as shown in FIG. 23B, (labeled "potentiation
response" curve). The solid curve depicted in FIG. 23D (labeled
"Net Benefit" curve), combines physiologic benefit from excitatory
RPS stimulation and arrhythmia risk. It is most desirable to
stimulate a little bit longer than (i.e., beyond) the
refractory/nonrefractory boundary. The dashed Net Benefit curve
shows that nonexcitatory neurostimulation (NES) is best delivered
on the "short side" of the refractory/nonrefractory boundary (or
else excitation could result). The present invention includes
methods to help the clinician or automated device find this
refractory/nonrefractory boundary and thus achieve the benefits of
the intended therapies while controlling risk.
[0210] Referring now to FIG. 24, which is a graphical depiction of
electrical and hemodynamic detection of cardiac chamber capture.
The trace labeled "1" is a ventricular electrogram (VEGM) obtained
from the site of application of the stimulation therapy. The trace
labeled "2" is a second electrogram that is near both right atrium
and right ventricle and is away from the site of application of the
pacing therapy. The trace labeled "3" is a surface ECG, traced "4"
is a record of arterial blood pressure (ABP), trace "5" is a record
of left ventricular pressure (LVP), trace "6" is a record of right
ventricular pressure (RVP) and trace "7" is a marker channel record
of stimulation therapies applied to the ventricles (Vtherapy). FIG.
24 illustrates embodiments of the concept of the identification of
whether or not a cardiac potentiation therapy lies inside or
outside the cardiac refractory period.
[0211] With respect trace 7, arrow 19 identifies a therapy is
delivered to the ventricle that lies inside the refractory period,
arrow 20 identifies a therapy that lies outside the refractory
period. With respect to trace 1, arrow 8 identifies an electrogram
tracing following a therapy that shows no evidence of a resultant
depolarization, confirming that the therapy lies in the refractory
period, and arrow 9 identifies an electrogram tracing showing a
cardiac depolarization following the therapy, confirming that the
therapy pulse captured, had sufficient amplitude and duration, and
was outside the refractory period.
[0212] Similarly, with respect to trace 2, arrows 10 and 11
identify noncapture and capture, respectively, from the electrogram
at an auxiliary electrode site suitable to identify pulses inside
and outside of the cardiac refractory period by the absence or
presence of a ventricular depolarization. With respect to trace 3,
arrows 12 and 13 identify the absence and presence of ventricular
depolarizations on a surface ECG, respectively.
[0213] An embodiment of the invention would be to apply a detection
algorithm to electrogram signals (possibly including but not
limited to signal traces 1-3) and identifying the presence or
absence of an evoked depolarization. This information is then used
to identify whether the preceding therapy was inside or outside of
the cardiac refractory period.
[0214] With respect to trace 4, arrow 14 points to a significantly
augmented ABP wherein the arterial pulse pressure on the cardiac
cycle following a therapy that lies outside the refractory period
was augmented. Similarly, LVP (trace 5) and RVP (trace 6) are also
augmented on the cycle following capture. Thus, FIG. 24 illustrates
an embodiment of the invention used to detect the presence of
pressure, flow, acceleration, impedance change, or other favorable
evidence of mechanical augmentation following therapy delivery.
This evidence also helps identify whether or not the preceding
therapy was delivered inside or outside of the cardiac refractory
period.
[0215] With respect to traces 5 and 6, arrows 15 and 17 indicate
portions of a left and right ventricular pressure waveform,
respectively, resulting from stimulation therapy delivered in the
cardiac refractory period. As a result, no evidence of an
extra-systole is seen following the therapy.
[0216] Again with respect to traces 5 and 6, arrows 16 and 18 are
pressure waveforms following a therapy delivered outside of the
cardiac refractory period. An extra-systole can be seen following
this therapy. Another embodiment of the invention is adapted to
apply a detection algorithm to a sensor that makes a measurement of
cardiac mechanical activity, including but not limited to right
ventricular, left ventricular or arterial pressure, dimension, or
acceleration and identifying the presence or absence of an extra
systole. This information is used to identify whether the preceding
therapy was inside or outside of the cardiac refractory period.
Evoked R wave detection information may then be used to time or
trigger delivery of a stimulation therapy that would cause post
extra-systolic potentiation or would be nonexcitatory for
neurostimulation, or both.
[0217] FIG. 25 depicts three traces, VEGM, ECG and Vtherapy,
respectively which can be used to determine whether or not capture
has occurred by analyzing a T wave. Trace 1 is a ventricular
electrogram (VEGM) from the site of application of the stimulation
therapy, trace 2 is a surface ECG, and trace 3 is a marker channel
record of applied stimulation therapies. With respect to trace 1
and 2, arrows 4 and 7 are electrogram signals indicating a
ventricular depolarization and arrows 5 and 8 are signals showing a
resulting ventricular repolarization or T-wave. In trace 3, arrow
10 corresponds to a marker of the delivered therapy, which was
applied just after the T-wave. In traces 1 and 2, arrows 6 and 9
indicate the resultant depolarization from the applied therapy.
[0218] Another embodiment of the therapy capture aspect of this
invention is used to identify the evoked T-wave from an electrogram
signal following application of a therapy pulse. A further
embodiment is to rely directly on the time of occurrence of the
T-wave (between the depolarization and repolarization from an
electrogram signal) to form an index of the boundary between
refractory (before the T-wave) and nonrefractory (after the T-wave)
intervals. The T-wave detection information may then be used to
time or trigger delivery of a stimulation therapy that would cause
post extra-systolic potentiation or would be nonexcitatory for
neurostimulation, or both.
[0219] FIG. 26 is a flow chart that diagrams response to capture
information to apply nonexcitatory neurostimulation (NES) therapy.
Following a ventricular pace or sense event, the sensing circuits
remain active and a timer counts down a delay until the scheduled
delivery of the NES stimulation pulse(s). If there has been no
intrinsic event in this interval, the NES pulse(s) are delivered
and electrogram or mechanical sensor signals employed (such as
described herein above) to determine if capture and an extrasystole
occurred. If capture did occur, the delivery time, stimulation
amplitude, or pulse number is decreased and the process repeated.
The value for Tdelay is typically 10-120 ms. Tdelay and other
stimulus parameters may also be influenced by observations of heart
rate or other physiologic sensors in addition to the electrical and
mechanical parameters discussed above.
[0220] FIG. 27 is a flow chart that diagrams response to capture
information to apply excitatory RPS therapy. Following a
ventricular pace or sense event, the sensing circuits such as
depicted in FIG. 3A and FIG. 3B remain active and a timer counts
down a delay until the scheduled delivery of the RPS stimulation
pulse(s). If there has been no intrinsic event in this interval,
the pulse(s) are delivered and electrogram or mechanical sensor
signals employed (such as described herein above) to determine if
capture and an extrasystole occurred. If capture did not occur, the
delivery time, stimulation amplitude, or pulse number is increased
and the process repeated. The value for Tdelay is typically 200-300
ms. Tdelay and other stimulus parameters may also be influenced by
observations of heart rate or other physiologic sensors in addition
to the electrical and mechanical parameters discussed above. This
algorithm is also used for the pulse(s) intended to produce RPS
when accompanied by NES pulse(s).
[0221] The identification of refractory and non-refractory
intervals and appropriate timing of pulses may operate using a
variety of timing schemes and sensing circuits which are both
preferably microprocessor or hardware controlled and programmable
with input values determined by algorithms or clinicians, such as
depicted in the system diagrams of FIG. 3A and FIG. 3B.
[0222] Detailed Description of Management of SVT with RPS
Therapy.
[0223] FIG. 28 is a series of four X-Y plots (labeled A-D)
illustrating deceleration of a rapid SVT by applying RPS therapy
according to one embodiment of the present invention. Such a rapid
SVT results when ectopic or reentrant rhythms involve the atria or
AV node and conduct to the ventricles (trace A). Conduction to the
ventricles is so rapid as to impair filling and ejection and as a
result pressures and flows are typically impaired (trace B). The
introduction of excitatory RPS stimulation pulses (denoted Vth in
trace C) creates additional refractory time in the ventricles and a
2:1 rate reduction takes place. Furthermore, potentiation and
enhanced mechanical function results (as seen in D). The net result
is an effective rate reduction with improved hemodynamic
performance. This RPS therapy regimen not only transforms a
potentially life threatening SVT into a well tolerated rhythm, but
allows more time for termination of the arrhythmia by natural,
device, or drug means.
[0224] The deceleration of rapid SVT by RPS therapy may operate
using a variety of timing schemes and sensing circuits which are
both preferably microprocessor or hardware controlled and
programmable with input values determined by algorithms or
clinicians, such as depicted in the system diagrams of FIG. 3A and
FIG. 3B.
[0225] Detailed Description of Feedback Control.
[0226] FIG. 29 is composed of two X-Y plots illustrating basic
control relationships for NES and RPS stimulation. In FIG. 29, the
index of cardiac mechanical function is taken to be dP/dt max as a
percentage of baseline, although other variables such as arterial
pulse pressure or cardiac output may be used. In the top X-Y plot
appearing near the top of FIG. 29, the RPS potentation response is
seen to be governed by the timing of stimulation that elicits an
extrasystole. It is not affected by stimulation intensity and needs
to be outside of the refractory period (here shown as 0-200 ms).
Non-excitatory neurostimulation, however needs to be nonexcitatory
and for electrodes near the heart this means inside the refractory
period. NES is also strongly dependent on stimulation intensity
(here shown as current in mA but may also include voltage, pulse
duration or the number of multiple pulses).
[0227] FIG. 30 is composed of two X-Y plots illustrating the need
to adjust stimulation parameters to maintain desired level of
enhanced function. Variations across and within subjects of
response to stimulation occur and can impact the resulting level of
enhanced function. For both RPS potentiation and NES
neurostimulation this may take the form of shifts in the absolute
level of response (or offset) but for convenience this has been
removed by normalizing to a non-stimulated baseline in the recent
past of 100%. The remaining variation takes the form of shifts in
the slope or the NES response, but for RPS takes on both changes of
slope (change of dP/dt max per unit time) as well as shifts in the
refractory period where no potentiation results. As a result, a
stimulation time that once gave the desired level of enhancement
may now be associated with no enhancement, more or less mechanical
function enhancement of the heart, and a different slope. In order
to maintain a level of beneficial effect on cardiac function, some
sort of closed loop control of stimulation is necessary.
[0228] FIG. 31 is a flow chart of depicting a means to control the
level of enhanced cardiac function. Adjustments in stimulation
timing or amplitude act on the heart and associated tissues and
organs and are observed by electrical, mechanical, metabolic, or
other physiologic sensors. In the most elementary situation, a
clinician observes this sensor information and adjusts the
stimulation accordingly. This may be thought of as closing the loop
but results in a slow response time. Implantable or external device
implementations of this invention may also close the loop more
promptly by following a control algorithm in a portion of the
therapy delivery device termed a controller. As with all practical
control systems, provision for manual override and tuning of the
controller are provided. This aspect of therapy control may be
considered separately from the start/stop and safety lockout rules
described elsewhere.
[0229] FIG. 32 is a block diagram illustrating a basic PID
controller for automatic adjustment of stimulation therapy. One of
the most basic of automatic control schemes is the PID controller
depicted in FIG. 32. A target level (or setpoint) is compared with
the actual level derived from a sensor and the difference is
referred to as the error. In a PID controller, there is a
proportional pathway with an associated multiplicative constant P,
a pathway that integrates the error with constant I, and a pathway
that works with the derivative of the error with constant D.
Practical PID controllers usually implement absolute limits to the
commanded output and similarly limit the integral of error (a
property called anti-windup limiting). Furthermore these
controllers are also usually implemented in a fashion such that the
transition from manual or fixed output to automatic control output
occurs smoothly (a property called bumpless transfer). In the
present application, this controller updates stimulation parameters
once per cardiac cycle with relatively straightforward computations
and thus is not a significant burden to the processing power of
implanted or external medical instrumentation.
[0230] FIG. 33 depicts a series of empirical measurements that
illustrates the effect of a P+I controller maintaining RPS cardiac
enhancement. A P+I controller was employed using RV dP/dt max as
the control variable and the results are shown here. A setpoint of
700 mmHg/s was entered (which was significantly greater than the
baseline level of 280 mmHg/s). Limits for the RPS therapy pulse's
timing were established (here 250 to 400 ms was used) and the
therapy initiated. The desired level of enhanced function was
achieved rapidly and the mean level of RV dP/dt max remained around
the setpoint as the feedback controller continuously adjusted the
timing (Tdelay). Incorporation of an integrator in the feedback
loop assures the mean error is zero. In this patent disclosure, the
inventors report that they increased the controller gain to the
point where oscillations developed, an instability phenomenon well
known in the area of feedback control. RPS stimulation not only
decreased heart rate from 90 to 50 bpm, but also resulted in a
simultaneous and sustained increase in LV dP/dt max from about 1100
to 2600 mmHg/s. A significant feature of this invention is that in
the process of adjusting RPS stimulation timing to maintain a
desired level of enhanced function, the controller automatically
adapts to changes in the potentiation response curve. This keeps
the controller clear of the refractory period and in an operating
region where linear feedback control applies. Similar linear
feedback controllers may be applied to NES neurostimulation and
combined NES and RPS stimulation. Such controllers also act in
concert with rules for starting and stopping stimulation therapy
and safety lockout rules as described elsewhere in this
invention.
[0231] The feedback control may operate using variations of the
controllers described which are preferably microprocessor or
hardware controlled and programmable by algorithms or clinicians,
such as depicted in the system diagrams of FIG. 3A and FIG. 3B.
[0232] Detailed Description of Extensions to Tachyarrhythmia
Management Devices.
[0233] FIG. 34 is a flow chart depicting a technique for extending
usual shock algorithms for ICDs and AEDs to facilitate NES and/or
RPS therapy. Another important aspect of this invention is the
recognition that certain seriously compromised states formerly
believed almost uniformly fatal such as EMD or PEA, may in fact
respond to electrical stimulation therapy. Present generation ICD
and AED devices may then be altered to reflect this possibility.
This flow chart illustrates some significant changes. First, it
introduces the RPS, NES, or combined stimulation therapies
described elsewhere in this invention into the device's algorithm
by checking for the presence of severe hemodynamic dysfunction
after tachyarrhythmia termination and applying therapies. Then, if
more than a set number of shocks (n) are delivered in a single
episode or cluster of episodes, more time consuming and accurate VF
detection rules are instituted to reduce the risk inadvertently
shocking rhythms that do not respond to shocks while still
maintaining the capability to recognize and treat VF. The potential
negative impact of slower VF detection is now balanced by less risk
of inadvertent shocks and an implementation of stimulation therapy
to assist in recovery of longer duration tachyarrhythmias. Finally,
the flow chart introduces a further analysis of surface ECG or
intracardiac electrogram signals or other sensors following an
extended but unsuccessful effort to end the tachycardia. The device
or the device and clinician look for features that are associated
with an improved success rate for tachyarrhythmia conversion such
as fine VF. Although current thinking is that the survival rate
when responding to shocks or ATP therapies this late into a
tachycardia episode is too poor to warrant therapies, the
stimulation therapy invention described herein appears to have
opened the door to further life saving and life sustaining
therapies.
[0234] An additional aspect of the present invention is to modify
existing rhythm recognition algorithms of implanted and external
therapy devices to accommodate operating concurrently with therapy
pulses delivered by a preexisting external or implanted device
respectively. The sharp changes in electrogram slew rate associated
with stimulation pulses may be recognized and ignored for the
purpose of automated rhythm recognition. Further, closely coupled
pairs of ventricular depolarizations with stimulation pulses
detected shortly before the second depolarization, in the setting
of cardiac dysfunction, are presumed to be RPS extrasystoles and
not an intrinsic bigeminal tachycardia rhythm. The devices analyze
the effective heart rate and rhythm accordingly and do not falsely
detect or treat tachyarrhythmias.
[0235] Diagram of Integrated RPS, NES, Defibrillation and Pacing
Concepts
[0236] FIG. 35 is a flowchart illustrating significant aspects of
stimulation therapies according to some aspects of the present
invention described herein. Various components of this invention
work together to provide safe and effective stimulation therapies
for cardiac dysfunction, including arrhythmias and HF, among
others. Beginning with the upper left portion of FIG. 35, block 4
incorporates the rules by which therapy as a whole is initiated or
terminated, thus this aspect (block 4) encloses the others in the
dotted border. This aspect may be an automated algorithm or may
require input from a clinician or the patient. Block 6 depicts the
closed loop feedback controller that gathers a measure of cardiac
function from the mechanical sensors and a desired control point
from the clinician or patient. The controller depicted as block 6
then adjusts the timing or the amplitude of the therapy to achieve
this desired control point. Block 5 includes the algorithms used to
identify the refractory period of the heart which uses as an input
either electrical sensing of cardiac depolarizations or
repolarizations or mechanical sensing of extra-systoles or
potentiation. If non-excitatory neurostimulation (NES) is desired,
the algorithm keeps the therapy timing within the refractory
period. In the case of RPS stimulation, the refractory period is
avoided. Block 5 can also be viewed as a range limiting system, it
limits the range of therapy timings that it receives from the
feedback controller. Block 3 includes the algorithms that lock out
therapy if an abnormal cardiac event such as a premature
ventricular contraction or a tachyarrhythmia occurs. Block 1 is the
dual-chamber pacing engine of the device, incorporating full dual
chamber sensing/pacing capability with the added functionality of
atrial coordinated pacing (ACP) with RPS therapies. Finally, block
7 is a defibrillation system including detection of tachyarrhythmic
events and application of either shock or pacing therapies such as
ATP to terminate these events. The system also includes new rules
to increase survivability of long duration episodes of tachycardia
or dysfunction normally associated with high-mortality.
[0237] While the various components depicted in FIG. 35 preferably
are integrated into a single medical device not all such components
must be included in any particular medical device. In fact, the
components may be distributed between remote devices and coupled
wirelessly or otherwise to perform accordin to the foregoing
description. Medical devices employing such components may comprise
IMDs, AED or other external medical devices, device programmers,
temporary pacing/defibrillation devices and the like.
[0238] FIG. 36 is a diagram illustrating an embodiment of the
present invention embodied into a conventional AED device. In one
form of this embodiment, such a conventional AED has a cardiac
pacing system adapted for TCP (such as pace/sense circuit 32).
While not depicted, the user interface would be reconfigured to
display appropriate pacing and sensing indicators and enhanced
microprocessor capability to handle TCP.
[0239] In another form of this embodiment, a conventional AED is
configured for RPS and/or NES therapy delivery according to the
present invention. Suitable AED circuitry for delivery of RPS
and/or NES therapy may be located within pace/sense circuit 32.
While not depicted, the user interface would be reconfigured to
display appropriate pacing and sensing indicators and enhanced
microprocessor capability to handle RPS and NES therapy. This form
of the invention is preferably based almost exclusively upon
electrical signals derived from surface electrodes.
[0240] In yet form of this embodiment, an AED would beneficially
include various physiologic sensors to better assess the degree of
cardiac dysfunction and response to delivered therapies (e.g.,
defibrillation, RPS, NES, TCP and the like). As depicted in FIG. 36
one or more sensors 1,2,3 may be coupled to the AED to assess the
need and efficacy of therapy. Examples of such sensors include a
pulse oximeter 1, a non-invasive blood pressure sensor 2, a
capnometer (i.e., an expired CO.sub.2 sensor) 3 and the like. In
combination with such sensors signal conditioning circuitry 4,5,8
are preferably coupled to amplify and filter such signals and make
them available to the microprocessor and related circuitry of the
AED.
[0241] One significant advantage of all forms of this embodiment
that include RPS results from the fact that conventional AED
defibrillation frequently immediately terminates a lethal rhythm
but often fails to restore adequate cardiac function. As a result,
a victim of sudden cardiac arrest oftentimes rapidly or eventually
succumbs to cardiac dysfunction or EMD/PEA. An AED configured to
deliver RPS therapy promptly following termination of the
tachyarrhythmia beneficially attempts to restore adequate cardiac
function. Prompt restoration of cardiac mechanical function is
exceptionally critical immediately following termination of such a
potentially lethal tachyarrhythmia and is provided by this aspect
of the present invention.
[0242] The following examples are intended as illustrative and are
not intended to be limiting of the scope of the claimed
invention.
EXAMPLE 1
AED Example with Presentation of VF
[0243] Despite the increasing availability to quick access
defibrillation by the public and quickening response times, the
prognosis of a victim of a sudden cardiac arrest surviving to a
hospital discharge is low, with many of these victims succumbing to
electromechanical dissociation (EMD) or pulseless electrical
activity (PEA). Current AED technology is equipped to treat
tachyarrhythmias but has no means to treat EMD/PEA.
[0244] An AED equipped with the features detailed in this invention
would address these scenarios. In an example implementation, the
AED would appear identical to the first responder. The responder
would place two transthoracic self-adhesive electrodes on the
patient and depress a start button on the device. The AED would
then obtain a surface ECG from the transthoracic electrodes and
apply a VF detection algorithm to the signal. If VF was detected,
the AED would apply a defibrillation shock and then apply a
re-detection algorithm. If VF stopped or was never present, the
device would check to see if the patient was in a bradyarrhythmia
or asystole and then would apply pacing therapies through the
transthoracic electrodes if needed. Furthermore, upon sensing a
sinus rhythm or during a paced rhythm, the device would request for
the responder to obtain a pulse from the victim. If a pulse was not
detected, the responder would press a button on the AED, which
would initiate RPS/NES therapies, delivered through the
transthoracic electrodes. The device would periodically request
additional pulse checks and would have an abort button clearly
labeled, allowing the responder to terminate therapy should the
victim regain consciousness.
[0245] Alternatively, the AED would be connected to a sensor that
made a non-invasive measurement of cardiac function such as a pulse
oximeter or a non-invasive blood pressure device such as a
inflatable arm cuff. Such a system would not require the responder
to make assessments of the victims pulse and would automatically
start and stop RPS/NES therapy as needed.
EXAMPLE 2
ICD Example with Presentation of VT
[0246] ICD systems provides patients with greatly improved
survivability from episodes of sudden cardiac arrest when compared
to patients treated with AED's mainly because there is minimal time
to wait between the onset of the arrhythmia and delivery of therapy
when the device is implanted and always ready to detect events.
However, some patients, especially those with more pronounced HF,
may not tolerate well even the shortest of VF episodes and may have
depressed cardiac function long after the arrhythmia is terminated.
Additionally, circumstances may arise that lengthen the duration of
the tachyarrhythmia before the device delivers a therapy. Some
tachyarrhythmias pose detection problems for ICD's, which may
postpone delivery of therapy. An arrhythmia could also require
several shocks to terminate, further prolonging the episode.
[0247] During a tachyarrhythmia, the coronary blood flow perfusing
the heart can become severely impaired, leading to ischemia and a
temporary loss in cardiac contractility referred to as stunning. If
the loss in contractility is severe enough to prevent restoration
of coronary flow once the arrhythmia is terminated, further
ischemia will result, leading to further diminishment of
contractility in a downward spiral. A therapy to quickly restore
contractility can break this cycle and lead to restoration of
sustained cardiac function.
[0248] An example of a RPS/NES stimulation therapy would include
treating impaired cardiac mechanical function following a
tachyarrhythmia. In an example scenario, an ICD equipped with such
a therapy would log the duration of any detected tachyarrhythmia.
If the duration of the episode exceeded a programmable threshold
before being terminated, indicating that the likelihood was high
that cardiac mechanical function was severely impaired, the device
would initiate a NES/RPS therapy for a fixed duration following the
episode to provide a quick boost in hemodynamics to hasten
re-perfusion of the heart and allow a more complete recovery from
the tachyarrhythmia. Alternatively, an RV pressure sensor could
detect RV pulse pressure following the episode and compare it to a
baseline value measured and stored before the episode was detected.
Should the RV pulse pressure fall shy of the baseline value for too
great of a time following the tachyarrhythmia, indicating prolonged
periods of depressed cardiac mechanical function, the ICD would
initiate RPS/NES therapies and then terminate the therapies after
the RV pressure reached some percentage of the baseline
measurement, indicating that the cardiac function was restored.
EXAMPLE 3
HF Example with Presentation of Acute Decompensation
[0249] Advanced stage HF patients experience sudden worsening of
heart failure associated symptoms which require hospitalization.
The transition from chronic compensated HF to acute decompensated
HF may result from a number of factors including dietary
indiscretion, progress of HF disease, and acute myocardial
infarction. When severe, symptoms may progress in a few hours to a
stage where these patients need to be admitted to a critical care
hospital bed, monitored by physiologic sensors, and treated with a
variety of drugs including intravenous inotropes. A patient
experiencing such a decompensation commonly exhibits low cardiac
output at rest, poor contractile function and low dP/dt max, slow
relaxation and high tau, elevated diastolic ventricular pressures,
and reduced ventricular developed pressures.
[0250] Cardiac resynchronization therapy delivered by an implanted
device is an important adjunct to good medical therapy. Such a
resynchronization device possesses electrodes and circuitry suited
to deliver NES and/or RPS stimulation therapy. Implantable
monitoring technology to continuously monitor cardiac performance
using RV pressure is undergoing clinical trials. In this scenario,
the implantable device is equipped to provide stimulation therapies
and monitor hemodynamic function as taught by this invention.
[0251] Upon detection of a rise of RV diastolic pressure and
decreased contractility assessed by dP/dt from a mean value
established over the past 2-4 weeks, RPS therapy may be initiated
with a single 2.0 V, 0.5 ms ventricular pulse delivered 260 ms
after a Vsense event from a RV apex bipolar lead. At this point the
patient may only experience a mild worsening of HF symptoms.
[0252] In this scenario, the response to this therapy is an almost
immediate doubling of dP/dt max, increased stroke volume and
ejection fraction, increased cardiac output, and reduced heart
rate. Over the course of a few hours, the improved hemodynamics
allow the kidneys to remove excess salt and water and RV diastolic
pressure falls back to baseline levels. Stimulation therapy is
painless and automatically started and discontinued without being
noticed by the patient. Interrogation of the implanted device's
memory reveals the episode described above and is credited with
preventing hospitalization or an emergency department visit.
EXAMPLE 4
SVT Example with Poor Toleration of High Rate
[0253] Supraventricular tachycardias that result in rapid
ventricular rates may be poorly tolerated, particularly in patients
with a history of heart failure. In this scenario the patient
experiences first symptoms of dizziness and palpitations (a
sensation of a fluttering within the chest). Upon evaluation by
emergency medical personnel, the heart rate is found to be 220 bpm.
Over the next few minutes, the patient's blood pressure drops, and
the patient becomes pale, sweaty and confused. An AED device
instrumented with NES and RPS therapies as described in this
invention is attached to the patient by a pair of adhesive pad
electrodes.
[0254] The fast but narrow ECG complexes allow the device to
diagnose a serious SVT and the operator is presented with the
option of a trial of RPS stimulation or cardioversion. After
administering a sedative/analgesic, a 5 minute trial of RPS
stimulation is begun by delivering 20 ms pulses of 60 mA timed 250
ms after surface ECG ventricular sense events. Vital signs,
evaluated by the emergency personnel document that heart rate drops
from 220 to 110 bpm and that blood pressure increases from 90/50 to
120/60. The patient becomes more lucid and notably more pink.
Before the 2 minute trial is completed, the rhythm spontaneously
converts to a sinus rhythm at 120 bpm. The AED recognizes this and
ends its stimulation therapy immediately.
[0255] A patient with a history of HF may not tolerate a
tachyarrhythmia well for more than a few minutes. If the rate is
high enough, patients often loose consciousness and their rhythms
deteriorate into VF. Despite prompt and good care, defibrillation
after a prolonged several minutes of cardiac ischemia may result in
EMD/PEA or asystole and death. This patient was indicated for
urgent pharmacologic or electrical cardioversion shock therapy and
avoided both. While the foregoing has been described as employing
RPS alone (with incidental NES therapy due to the location of the
surface electrode and magnitude of the stimulation), it may be
desirable to intentionally invoke NES alone or in combination with
RPS therapy. This may be advantageously employed by using one or
more dedicated electrodes.
[0256] The above-described methods and apparatus are believed to be
of particular benefit for patient's suffering heart failure
including cardiac dysfunction, chronic HF, and the like and all
variants as described herein and including those known to those of
skill in the art to which the invention is directed. It will
understood that the present invention offers the possibility of
monitoring and therapy of a wide variety of acute and chronic
cardiac dysfunctions. The current invention provides a system and
method for delivering therapy for cardiac hemodynamic dysfunction,
which without limitation, may include one of the following
features:
[0257] Therapy for cardiac dysfunction that might otherwise require
inotropic drugs such as dobutamine, calcium, or milrinone;
[0258] Therapy for cardiac dysfunction that might otherwise require
mechanical aids such as intra-aortic balloon pumps, cardiac
compression devices, or LV assist device pumps;
[0259] An implantable or external device that continuously monitors
the patient, automatically administering therapy when physiologic
sensors indicate need or the patient experiences symptoms;
[0260] Treatment for cardiac dysfunction as a result of drug
overdose or hypothermia;
[0261] Combined with negative inotrope drug treatments such as beta
blockers to improve patient tolerance of these treatments;
[0262] Therapy for post ischemic cardiac dysfunction or stunning
such as following coronary vessel occlusion, thrombolytic drugs,
angioplasty, or cardiac bypass surgery;
[0263] Support for the dysfunction that is associated with coming
off cardiac bypass and the use of cardioplegia;
[0264] Therapy for rapid and poorly tolerated supra-ventricular
tachycardias (SVT) by regularizing 2:1 AV block, lowering
mechanical heart rate and improving mechanical function, and may
facilitate arrhythmia termination;
[0265] Management of dysfunction following tachycardic events
including AT, AF, SVT, VT, or VF including elective cardioversion
and urgent defibrillation and resuscitation;
[0266] Severe bouts of heart failure, worsening to cardiogenic
shock, electromechanical dissociation (EMD) or pulseless electrical
activity (PEA)
[0267] Acute deterioration of cardiac function associated with
hypoxia or metabolic disorders;
[0268] Intermittent therapy for HF such as prior or during exertion
or for worsening symptoms;
[0269] Continuous therapy for HF to modify heart rate, improve
filling and mechanical efficiency, and facilitate reverse
remodeling and other recovery processes;
[0270] Scheduled therapy for HF including use for a specified
interval of time at a particular time of day or scheduled delivery
every N cardiac cycles;
[0271] Atrial RPS therapy to increase atrial contractility,
facilitate better ventricular filling, and AV synchrony; and/or
[0272] Reducing AF burden as a result of reduced atrial loading and
better ventricular function during therapy.
[0273] Consequently, the expression "heart failure" as used in
above and in the following claims shall be understood to embrace
each of the foregoing and conditions related thereto. All patents
and other publications identified above are incorporated herein by
reference.
[0274] While the present invention has been illustrated and
described with particularity in terms of preferred embodiments, it
should be understood that no limitation of the scope of the
invention is intended thereby. The scope of the invention is
defined only by the claims appended hereto. It should also be
understood that variations of the particular embodiments described
herein incorporating the principles of the present invention will
occur to those of ordinary skill in the art and yet be within the
scope of the appended claims.
* * * * *