U.S. patent application number 14/539273 was filed with the patent office on 2015-03-12 for method and apparatus to control conduction through the heart to treat cardiac conditions.
The applicant listed for this patent is Medtronic, Inc.. Invention is credited to Daniel C. Sigg, Michael R. Ujhelyi.
Application Number | 20150073288 14/539273 |
Document ID | / |
Family ID | 37491739 |
Filed Date | 2015-03-12 |
United States Patent
Application |
20150073288 |
Kind Code |
A1 |
Ujhelyi; Michael R. ; et
al. |
March 12, 2015 |
METHOD AND APPARATUS TO CONTROL CONDUCTION THROUGH THE HEART TO
TREAT CARDIAC CONDITIONS
Abstract
Control of conduction through a heart is described. A lead with
a proximal end and a distal end is provided. The distal end of the
lead is inserted into a target area. An agent is delivered through
the lead to the target area. Delivery of the agent is monitored via
a closed loop feedback system.
Inventors: |
Ujhelyi; Michael R.; (Maple
Grove, MN) ; Sigg; Daniel C.; (St. Paul, MN) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Medtronic, Inc. |
Minneapolis |
MN |
US |
|
|
Family ID: |
37491739 |
Appl. No.: |
14/539273 |
Filed: |
November 12, 2014 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
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11192884 |
Jul 29, 2005 |
8892197 |
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14539273 |
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Current U.S.
Class: |
600/518 ;
604/503; 607/3 |
Current CPC
Class: |
A61M 5/14276 20130101;
A61N 1/365 20130101; A61M 5/1723 20130101; A61N 1/3682 20130101;
A61B 5/046 20130101; A61N 1/0575 20130101; A61M 2230/04 20130101;
A61M 2005/1726 20130101; A61M 2210/125 20130101; A61M 2230/63
20130101 |
Class at
Publication: |
600/518 ; 607/3;
604/503 |
International
Class: |
A61M 5/172 20060101
A61M005/172; A61B 5/046 20060101 A61B005/046; A61N 1/368 20060101
A61N001/368 |
Claims
1-21. (canceled)
22. A method of treating atrial fibrillation in a patient, the
method comprising: delivering a therapeutic agent directly into AV
nodal tissue of the patient in response to a determination of
atrial fibrillation to decrease ventricular rate; monitoring an
electrical response by the heart to the delivered therapeutic agent
via a closed loop system, wherein monitoring the electrical
response comprises monitoring AV conduction time; and adjusting a
quantity of the therapeutic agent delivered directly to the AV
nodal tissue using the closed loop system until a preferred AV
conduction time is attained.
23. The method of claim 22, further comprising: determining whether
AV conduction time is greater than 100 ms; determining whether AV
conduction time is less than 250 ms; and continuing to deliver the
therapeutic agent directly into AV nodal tissue until preferred AV
conduction time is attained if the AV conduction time is greater
than 100 ms and less than 250 ms.
24. The method of claim 22, further comprising: determining whether
AV conduction time is less than 100 ms; and ceasing delivery of the
therapeutic agent in response to determining AV conduction time is
less than 100 ms.
25. The method of claim 24, further comprising: continuing to
monitor AV conduction time upon ceasing delivery of the therapeutic
agent in response to determining AV conduction time is less than
100 ms; and delivering therapeutic agent directly into AV nodal
tissue if AV conduction time becomes greater than 100 ms after
delivery was previously ceased.
26. The method of claim 22, further comprising: determining whether
AV conduction time is greater than 250 ms; and determining whether
AV block III is present in the patient in response to determining
AV conduction time is greater than 250 ms.
27. The method of claim 26, further comprising determining if
pacing is required in response to determining that AV block III is
present.
28. The method of claim 26, further comprising delivering a
quantity of therapeutic agent different than previously being
delivered if AV block III is not determined when AV conduction time
is greater than 250 ms.
29. The method of claim 22, further comprising: determining whether
AV conduction time is less than 250 ms; and delivering the
therapeutic agent directly into AV nodal tissue until a preferred
AV conduction time is attained if AV conduction time is less than
250 ms.
30. The method of claim 22, further comprising: determining whether
AV conduction time is greater than 100 ms; and delivering the
therapeutic agent directly into AV nodal tissue until a preferred
AV conduction time is attained if AV conduction time is greater
than 100 ms.
31. The method of claim 22, further comprising: determining whether
AV conduction time is greater than 100 ms; and determining whether
AV conduction time is greater than 250 ms in response to
determining AV conduction time is greater than 100 ms.
32. A method of treating atrial fibrillation in a patient, the
method comprising: delivering a therapeutic agent directly into AV
nodal tissue of the patient; monitoring an electrical response by
the heart to the delivered therapeutic agent via a closed loop
system, wherein monitoring the electrical response comprises
monitoring AV conduction time of the heart; adjusting a quantity of
the therapeutic agent delivered to the AV nodal tissue using the
closed loop system until a preferred AV conduction time is attained
if AV conduction time is greater than a lower AV conduction time
and less than an upper AV conduction time; ceasing delivery of the
therapeutic agent in response to determining AV conduction time is
less than the lower AV conduction time; and determining whether a
cardiac condition requiring pacing is present if the AV conduction
is greater than the upper AV conduction time.
33. The method of claim 32, wherein the lower AV conduction time is
100 ms and the upper AV conduction time is 250 ms.
34. The method of claim 32, wherein ceasing delivery of the
therapeutic agent in response to determining AV conduction time is
less that the lower AV conduction time comprises ceasing delivery
of the therapeutic agent in response to determining AV conduction
time is less than 100 ms.
35. The method of claim 32, further comprising: continuing to
monitor AV conduction time upon ceasing delivery of the therapeutic
agent upon determining AV conduction time is less than the lower AV
conduction time; and delivering therapeutic agent directly into AV
nodal tissue if AV conduction time becomes greater than the lower
AV conduction time after delivery was previously ceased.
36. The method of claim 32, wherein determining whether a cardiac
condition requiring pacing is present if the AV conduction is
greater than the upper AV conduction time comprises determining
whether AV block III is present in the patient in response to
determining AV conduction time is greater than the upper AV
conduction time,
37. The method of claim 36, further comprising determining if
pacing is required in response to determination that AV block III
is present.
38. The method of claim 36, further comprising delivering a
quantity of therapeutic agent different than previously being
delivered if AV block III is not determined when AV conduction time
is greater than the upper AV conduction time.
39. The method of claim 32, wherein adjusting a quantity of the
therapeutic agent delivered to the AV nodal tissue using the closed
loop system comprises: determining whether AV conduction time is
less than 250 ms; and delivering the therapeutic agent directly
into AV nodal tissue until a preferred AV conduction time is
attained if AV conduction time is less than 250 ms.
40. The method of claim 32, wherein adjusting a quantity of the
therapeutic agent delivered to the AV nodal tissue using the closed
loop system comprises: determining whether AV conduction time is
greater than 100 ms; and delivering the therapeutic agent directly
into AV nodal tissue until a preferred AV conduction time is
attained if AV conduction time is greater than 100 ms.
41. The method of claim 32, wherein monitoring AV conduction time
comprises: determining whether AV conduction time is greater than
100 ms; and determining whether AV conduction time is greater than
250 ms in response to determining AV conduction time is greater
than 100 ms.
Description
RELATED APPLICATION
[0001] This application is related to, and claims the benefit of,
provisionally-filed U.S. Patent Application Ser. No. 60/464,767
filed Apr. 23, 2003, and U.S. patent application Ser. No.
10/798,613 filed Mar. 11, 2004 entitled "System for the Delivery of
a Biologic Therapy with Device Monitoring and Back-Up", which are
incorporated herein by reference in their entirety. This
application is also related to, and claims the benefit of,
provisionally-filed U.S. Patent Application Ser. No. 60/684,658,
filed May 26, 2005.
FIELD OF THE INVENTION
[0002] The present invention relates generally to cardiovascular
therapies and, more particularly, to control of conduction through
the heart.
BACKGROUND OF THE INVENTION
[0003] Cardiac conditions such as supraventricular arrhythmias
(SVA) or chronic heart block are treated with device therapies,
drug therapies, or a combination thereof. Device therapies
typically involve implantable medical devices (IMDs). IMDs are
effective except with some patients that experience SVA or chronic
heart block. One such example relates to implantable pulse
generators (IPGs) or implantable cardioverter-defibrillators (ICDs)
that deliver electrical stimulation to the vagal nerve plexes
located in the heart. Stimulation of vagal nerve plexes enhances
parasympathetic input to the atrioventricular (AV) node and
subsequently slows AV nodal conduction and ventricular rate. While
this therapy operates acutely, tachyphylaxis may occur.
Tachyphylaxis is a rapidly decreasing response to a drug or
physiologically active agent after administration of a few doses.
Additionally, vagal stimulation may induce atrial arrhythmias.
[0004] Combined device and drug therapies are costly. One such
therapy relates to ventricular rate sensors of an IMD that rely on
a sensor-based algorithm to regulate the delivery of drugs. In this
case, drugs are typically taken orally on a daily basis regardless
of the existence of atrial fibrillation (AF) or inadequate
ventricular rate in a heart. A daily dosage is problematic for some
patients. For example, some patients are excessively bradycardiac
while in sinus rhythm and experience an elevated ventricular rate
in AF. To address this problem, a pacemaker is implanted to detect
"drug induced brady" conditions and to control the rate of drug
delivery. Pacemakers increase patients' costs.
[0005] Drug therapies also have drawbacks. Drugs are delivered
through systemic circulation of a patient. Examples of systemic
drug delivery include oral, intravenous, subcutaneous, or
transdermal delivery methods. Since systemic drug delivery
introduces drugs to all organs and tissue, non-targeted organs or
tissue may exhibit drug toxicity. Drug toxicity concerns limit the
dosage that is administered to a patient. Limiting a dosage may
reduce the effectiveness of the drug. Systemic drug delivery may
also cause side effects in the patient, which reduces tolerability
or effectiveness of drugs. For example, drugs that slow down AV
nodal conduction may cause side effects such as sinus bradycardia,
congestive heart failure, fatigue, or constipation.
[0006] Some gene therapies claim to chronically transfect AV nodal
tissue with specific genes to control conduction rate through the
AV node. However, it is unclear whether these gene therapies
adequately control titration of an agent to achieve therapeutic
goals. Consequently, gene therapy may result in uncontrollable or
inadequate AV nodal rate. It is therefore desirable to have
therapies that overcome the limitations described above.
BRIEF DESCRIPTION OF THE DRAWINGS
[0007] The present invention will become more fully understood from
the detailed description and the accompanying drawings,
wherein:
[0008] FIG. 1 is a block diagram of an exemplary system to control
conduction through a heart;
[0009] FIG. 2 is a partial perspective view of an exemplary medical
device that delivers therapeutic agent to myocardial tissue of a
patient;
[0010] FIG. 3 is a flow diagram of a method to detect cardiac
conditions;
[0011] FIG. 4 is a flow diagram of a method to treat cardiac
conditions when a patient has low physical activity;
[0012] FIG. 5 is a flow diagram of a method to treat cardiac
conditions when a patient has increased physical activity;
[0013] FIGS. 6A-6B are flow diagrams of a method to control atrial
ventricular conduction time;
[0014] FIG. 7 is a flow diagram of a method to detect cardiac
conditions;
[0015] FIG. 8 is a flow diagram of a method to treat cardiac
conditions;
[0016] FIG. 9 is a flow diagram of a method to treat cardiac
conditions based upon patient activity;
[0017] FIG. 10A is a bar diagram in which ventricular rate is
controlled;
[0018] FIG. 10B is a electrocardiogram in which ventricular rate is
controlled;
[0019] FIG. 10C is a block diagram of FIG. 10B in which ventricular
rate is controlled; and
[0020] FIG. 10D is a bar diagram of reversible increase of AH and
AV intervals during continuous administration of an agent.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0021] The following description of embodiments is merely exemplary
in nature and is in no way intended to limit the invention, its
application, or uses. For purposes of clarity, similar reference
numbers are used in the drawings to identify similar elements.
[0022] The present invention is directed to control of conduction
through a heart. This is accomplished, in part, by monitoring
delivery of an agent (e.g. drug, biologic, drug/biologic, etc.) to
a target area through a closed loop feedback system. Closed loop
feedback systems typically relate to implantable medical devices
(IMDs). An IMD includes a first and a second lead. The distal end
of the first lead is inserted into or around the target area (e.g.
atrialventricular (AV) nodal area etc.). The first lead then
delivers the agent to the target area. The IMD monitors the
electrical response from the heart by accessing data via an
electrode at a distal end of a second lead. Adjustments are made to
the amount of agent delivered based upon the sensed electrical
response from the heart by accessing data. In this manner, a
patient's ventricular rate is maintained at an optimal level.
[0023] A variety of cardiovascular conditions are treated through
control of AV conduction time. For example, the present invention
treats paroxysmal chronic supraventricular arrhythmias (i.e. atrial
fibrillation, atrial flutter, atrial tachycardia, supraventricular
tachycardia). Additionally, chronic heart block (i.e. chronic
atrial fibrillation (AF) conditions, chronic AV block conditions)
is also treated through the control of the ventricular rate or
atrialventricular conduction time. Episodic periods of AF with fast
ventricular response are also managed. Furthermore, the present
invention improves the treatment and management of atrial
bradyarrhythmias.
[0024] The present invention also improves treatment of
cardiovascular conditions. For example, drug dosages are reduced by
five to twenty fold. Additionally, low or undetectable systemic
plasma concentrations are obtained. Elimination or diminution is
achieved for non-cardiac and cardiac side effects (e.g. ventricular
proarrhythmia etc.). Non-orally bioavailable drugs can be
administered. Greater efficacy or duration of action is obtained.
Episodic drug delivery decreases the risk for drug toxicity and
complication. Episodic delivery also increases the time periods
between drug replacement in the implantable drug delivery
arrhythmia management system. A synergistic effect may be obtained
in combination with electrical stimulation therapies.
[0025] FIG. 1 depicts a block diagram of system 10 that treats
cardiac conditions (e.g. supraventricular arrhythmias, chronic
heart block etc.) by monitoring the effectiveness of an agent
delivered to myocardial tissue. System 10 includes IMD 12, one or
more leads 20a-20c, and agent reservoir 30. A detailed example of
an IMD 12 may be seen with respect to a U.S. patent application
Ser. No. 10/465,351 filed on Jun. 19, 2003, and assigned to the
assignee of the present invention, the disclosure, in relevant
part, is incorporated by reference. Exemplary IMDs 12 include an
IPG to provide a pacing function, an ICD to provide shocks, a
monitoring implant to record various cardiac performance
characteristics, or a device that combines these functions.
[0026] Leads 20a-20c, which extend from IMD 12, are inserted into
or around the myocardial tissue. For example, distal end of lead
20a is in the right atrium, distal end of lead 20b is in the right
ventricle, and distal end of lead 20c is in or in close proximity
to the AV node. Leads 20a-20c include electrodes to sense data
related to cardiovascular variables or parameters. Lead 20c also
includes a delivery line (not shown) that allows delivery of the
agent to the myocardial tissue. An agent delivery system 30,
coupled to lead 20c via conductive line 21, contains and pumps the
desired agent (e.g. drug, biologic agent, drug/biologic agent,
genetic material etc.) to the myocardial tissue. Line 21 is a
coaxial line that includes a conductive line (e.g. wire) and an
agent delivery line (not shown).
[0027] An exemplary catheter 18 to deliver therapeutic agent to
tissue is depicted in FIG. 2. Catheter 18 includes a catheter body
19, lead 20c and a fluid container 50. Lead 20c comprises a lead
body 22, one or more electrodes 24, and an anchoring mechanism 34.
Lead body 22 has a proximal end 35, a distal end 36, and a lumen
therebetween. Anchoring mechanism 34 (e.g. a fixed screw etc.),
disposed near distal tip 25 of lead 20c, is configured to secure
lead 20c to the myocardial tissue (e.g. AV nodal tissue etc.).
Ideally, lead 20c is affixed in or around the triangle of Koch of
the myocardial tissue. Fluid container 50 interconnects agent
delivery system 30 with the myocardial tissue. Fluid container 50
is guided through lead 20c and is either removed after the
procedure or left in place. Distal tip 55 of fluid container 50
either contacts the myocardial tissue or is forced into the
myocardial tissue.
[0028] System 10 operates as a closed loop feedback system. For
example, IMD 12 signals agent delivery system 30 over line 21 to
deliver an agent to myocardial tissue. Exemplary agents include
calcium channel antagonists, beta-adrenergic antagonists,
digitalis-derived drugs, purinergic agents (e.g. adenosine
compound, etc.), parasympathetic agents, (e.g. acetylcholine-like
compounds, etc.), local anesthetics, adrenergic agonists or other
suitable material. In response to signals from IMD 12, agent
delivery system 30 pumps agent via a pump (not shown) through lead
20c. The agent is delivered through the fluid container 50 and into
or onto the myocardial tissue. The agent regulates AV nodal
conduction. For example, the agent controls the speed at which a
depolarization wavefront passes from the atrium to the ventricule.
In the case of supraventricular tachycardias (SVT), the speed of
the depolarization wavefront is decreased. In contrast, the speed
of the depolarization wavefront is increased for AV nodal block.
Sensed data is then transmitted over one or more leads 20a-20c via
their respective electrodes 24 to IMD 12. Based upon the sensed
data, IMD 12 then determines whether an adjustment of the agent
dosage is required. If an adjustment is required, IMD 12 signals
agent delivery system 30 to increase, decrease, or stop agent
delivery.
[0029] FIGS. 3 through 6A-6B generally depict an embodiment to
monitor the effect of an agent on myocardial tissue and then, if
necessary, adjust the agent dosage. These operations are embodied
in computer instructions that are stored in memory (e.g. RAM) and
executed on the microprocessor of IMD 12. FIG. 3 specifically
relates to monitoring for cardiac conditions. At operation 100, a
patient's heart rate is sensed through the electrode(s) of one or
more leads 20a-20c. At block 110, a determination is made as to
whether an arrhythmia is occurring. If arrhythmia is not detected,
system 10 continues to sense data related to the heart rate at
block 100. Alternatively, if an arrhythmia is detected, the
ventricular rate is sensed by one or more of electrodes of leads
20a-20c at block 120. At block 130, a determination is made as to
whether an elevated ventricular response is occurring. An
undetected elevated ventricular response causes system 10 to return
to block 120 to continue to sense data related to ventricular rate.
If an elevated ventricular response is detected, the patient's
level of activity is sensed at block 140. At block 150, a
determination is made as to whether the patient is at rest. If the
patient is at rest, the operation goes to block 300 of FIG. 5. In
contrast, if the patient is at rest, the operation goes to block
200 of FIG. 4.
[0030] FIG. 4 is a flow diagram depicting a method to treat a
patient for cardiovascaular conditions while in an inactive
physical state (i.e. rest state). Generally, blocks 300-340 relate
to treatment of a high ventricular rate; blocks 350-380 relate to
maintaining a desirable ventricular rate; and blocks 410-480 relate
to treatment of a low ventricular rate. At block 300, agent
delivery to a target area (e.g. AV nodal area, etc.) occurs. At
block 310, a determination is made as to whether a high ventricular
rate is occurring. Typically, a high ventricular rate is greater
than 80 beats per minute (BPM). However, age, pre-existing disease,
pre-existing physiological sinus heart rate (if available) and
other factors are considered by the physician when programming the
ventricular heart rate levels. If high ventricular rate data is
sensed from the electrical activity of the myocardial tissue, IMD
12 signals agent delivery system 30 to increase the agent dosage
level at block 320. The elevated dosage level is also referred to
as a first dosage level. A determination is then made as to whether
the ventricular rate is within the desired range after the
administration of the first dosage level at block 330. A desired
ventricular rate range is typically greater than 60 BPM and less
than 80 BPM. If the ventricular rate is not within the desired
range after a certain time period, the agent is administered at
another elevated dosage level at block 320. For example, if the
ventricular rate exceeds 100 bpm for over 5 minutes at rest while a
drug is administered at a given dosage X, then dosage X is
increased 10-200% until the ventricular rate is within the desired
range. Alternatively, if the ventricular rate is determined to be
within the desired range, delivery of the agent in its current
dosage is continued at block 340.
[0031] If it is determined that a high ventricular rate does not
exist at block 310, the operation turns to maintenance of a desired
ventricular rate. A determination is made as to whether the
ventricular rate is within a desired range at block 350. If the
ventricular rate is below the desired ventricular rate, delivery of
the agent is stopped at block 400. If the ventricular rate is
within the desired range, the agent is continuously delivered in
its current dosage at block 360. A determination is then made as to
whether the arrhythmia has stopped at block 370. If the arrhythmia
has ceased, the agent is continuously delivered at its current
dosage to the target area at block 300. If not, a determination is
made as to whether the heart rate is too low at block 375. If the
heart rate is not too low, delivery of the agent is stopped at
block 380 and system 10 returns to monitoring cardiovascular
conditions at block 100 of FIG. 3. If the heart rate is too low, a
pacing operation is implemented at operation 420.
[0032] Blocks 400-480 generally relate to treatment of a low
ventricular rate. At block 400, delivery of the agent is stopped
for low range ventricular rate (e.g. typically less than 60 BPM).
At block 410, a determination is made as to whether pacing is
required. If pacing is required, pacing is performed at block 420
by one of the leads 20a-20c. At block 430, the heart rate is
monitored. At block 450, a determination is made as to whether the
heart rate is too low. If the heart rate is too low, the operation
makes a determination as to whether pacing is required at block
410. If the heart rate is not too low, a determination is made as
to whether the heart rate is too high at block 460. If the heart
rate is too high, the operation goes to block 310 to determine
whether a high ventricular rate exists. If the heart rate is not
too high, the agent is administered at a certain dosage level at
block 470. For example, if the heart rate is at 160 bpm during
exercise, then the AVN blocker drug such as calcium channel blocker
agent (e.g. verapamil etc.) is continuously delivered. A
determination is then made at block 480 as to whether the
arrhythmia has stopped. If the arrhythmia has stopped, delivery of
the agent is stopped at block 380. If the arrhythmia has not
stopped, the agent is delivered at a certain dosage level at block
470. This dosage level is referred to as a second dosage level.
[0033] FIG. 5 is a flow diagram that depicts treatment of a cardiac
condition based upon the activity of a patient instead of
ventricular rate. At block 500, agent delivery to a target area
(e.g. AV nodal area, etc.) occurs. At block 505, a determination is
made as to whether a patient exhibits high physical activity. U.S.
patent application Ser. No. 10/465,351, incorporated by reference,
in relevant part, briefly describes sensors for activity.
[0034] Typically, high physical activity is determined by increased
activity of these sensors (e.g. motion sensor, etc). If high
physical activity data is sensed from the electrical activity of
the myocardial tissue, IMD 12 signals agent delivery system 30 to
increase the agent dosage level at block 510. The elevated dosage
level is also referred to as a first dosage level. A determination
is then made as to whether the patient, who is experiencing high
physical activity, nevertheless maintains the heart beat within a
desired range after the administration of the first dosage level at
block 515. If the heart rate is not within the desired range within
a certain time period, the agent is administered at another
elevated dosage level at block 510. For example, the patient has a
ventricular rate of 180 bpm at a given dosage level X, then this
dosage level is increased by 10-200%. Alternatively, if the heart
rate is determined to be within the desired range, delivery of the
agent in its current dosage is continued at block 520.
[0035] If it is determined that a high physical activity does not
exist at block 505, the operation turns to medium level of physical
activity operations. A determination is made as to whether medium
physical activity is occurring at block 525. If the ventricular
rate is below the desired ventricular rate, delivery of the agent
is stopped at block 550. If medium physical activity is occurring,
the agent is continuously delivered in its current dosage at block
530. A determination is then made as to whether the arrhythmia has
stopped at block 535. If the arrhythmia has ceased, the agent is
continuously delivered at its current dosage to the target area at
block 500. If not, a determination is made as to whether the heart
rate is too low at block 540. If the heart rate is not too low,
delivery of the agent is stopped at block 545 and the system
returns to monitoring cardiovascular conditions at block 100 of
FIG. 3.
[0036] Blocks 550-585 generally relate to treatment of a patient
during low physical activity. At block 550, delivery of the agent
is stopped for low range ventricular rate (e.g. less than 60 BPM).
At block 555, a determination is made as to whether pacing is
required. If pacing is required, pacing is performed at block 560
by one of the leads 20a-20c. At block 565, the heart rate is
monitored. At block 570, a determination is made as to whether the
heart rate is too low. If the heart rate is too low, the operation
makes a determination as to whether pacing is required at block
555. If the heart rate is not too low, a determination is made as
to whether the heart rate is too high at block 575. If the heart
rate is too high, the operation goes to block 505 to determine
whether a high physical activity exists. If the heart rate is not
too high, the agent is administered at a certain dosage level at
block 580. For example, a calcium blocking agent may be delivered
if the ventricular heart rate is 160 beats per minute. A
determination is then made at block 585 as to whether the
arrhythmia has stopped. If the arrhythmia has stopped, delivery of
the agent is stopped at block 545. If the arrhythmia has not
stopped, the agent is delivered at a certain dosage level at block
580. This dosage level is referred to as a second dosage level.
[0037] FIGS. 6A and 6B depict operations to control AV conduction
time. At block 700, the heart rate is sensed by system 10. At block
710, AV conduction time is monitored. At block 720, a determination
is made as to whether AV conduction time too high. If AV conduction
time is not too high, the operation loops back to block 710 to
monitor AV conduction time. Alternatively, if AV conduction time is
too high, agent is delivered to the target area at block 730. At
block 740, a determination is made as to whether AV conduction time
is lower than 100 microseconds. If AV conduction time is not lower
than 100 milliseconds) (ms), a determination is then made at block
780 as to whether AV conduction time is less than 250 ms. In
contrast, if AV conduction time is lower than 100 ms, agent
delivery is stopped at block 750. At block 760, AV conduction time
is monitored. At block 770, a determination is made as to whether
AV conduction time is greater than 100 ms. If AV conduction time is
not greater than 100 ms, system 10 loops back to block 760 to
monitor AV conduction time. Alternatively, if AV conduction time is
greater than 100 ms, the agent is delivered to the target area at
block 730.
[0038] Turning now to block 780, a determination is made as to
whether AV conduction time is less than 250 ms. If AV conduction
time is less than 250 ms, delivery of the agent continues at its
current dosage at block 790.
[0039] At block 810, a determination is made as to whether AV block
III is occurring in the patient. If it is not present, agent
delivery continues at a specified dosage at block 820. The heart
rate is monitored and appropriate action is taken if a cardiac
condition is detected at block 825. Optionally, control of system
10 returns to block 700. In contrast, if AV block III is occurring,
a determination is made as to whether pacing is required at block
830. If pacing is required, a pacing operation is implemented at
block 840. The patient's heart rate is monitored at block 850. A
determination is made as to whether the heart rate is too low at
block 860. At block 865, the heart rate is monitored and
appropriate action is taken if a cardiac condition is detected.
Optionally, control of system 10 returns to block 700.
[0040] FIGS. 7-9 illustrate another embodiment to control
conduction through a heart. FIG. 7 depicts operations that
determine whether a therapeutic algorithm or a pacing algorithm are
implemented. At block 900, the heart rate of a patient is sensed.
At block 910, a determination is made as to whether atrial
arrhythmia is detected. If no atrial arrhythmia is detected, any
therapy is stopped at operation 915 and the system returns to
sensing the heart rate at block 900. If atrial arrhythmia is
detected, the patient's level of activity is sensed at block 920.
At block 930, the heart rate is determined. At operation 940, a
determination is made as to whether an elevated ventricular
response is present. If so, the therapeutic algorithm is
implemented at operation 950 and the operations in FIG. 8 are then
followed. If an elevated ventricular response is not detected, a
determination is made as to whether a low ventricular response is
present at block 960. If so, a standard pacing algorithm is
implemented at operation 970 and the operations of FIG. 9 are
implemented. However, if a low ventricular response is not
detected, control of the algorithm returns to the start
operation.
[0041] FIG. 8 is a flow diagram related to administration of a
therapeutic agent taking into consideration a patient's level of
physical activity. At operation 1000, an agent is delivered to the
target area (e.g. triangle of Koch area). At operation 1010, a
determination is made as to whether a condition is satisfied.
Exemplary conditions include the elapsed time from which the agent
was delivered to the target area, variables related to AF, slope of
heart rate change, or other suitable conditions. If the condition
is not satisfied, control of the operation returns to block 1000 in
which the agent continues delivery. In contrast, if the condition
is satisfied, the patient's level of activity is checked at block
1015. A determination is then made as to whether a low heart range
is present at block 1020. If a low heart range is present, a
determination is made as to whether a minimum dosage level is being
applied to patient at block 1030. If the minimum dosage level is
being used, delivery of the agent at target area is stopped at
block 1040 and control of the algorithm returns to block 100. In
contrast, if a minimum dosage level is not present, the agent
dosage is decreased at operation 1032 to control of system 10 then
turns to block 1000.
[0042] If a low heart range is not present in the patient, a
determination is then made at block 1022 as whether a normal heart
range is present. If the normal heart range is occurring, agent
dosage is maintained at block 1024 and control of system 10 returns
to block 1000. If a normal heart range is not present in the
patient, a determination is made as to whether the patient is being
administered at maximum agent dosage level at block 1028. If not,
agent dosage is increased at block 1029 and control of system 10
returns to block 1000. In comparison, if the patient is at the
maximum dosage level, a patient alert is sent to the physician at
block 1026 and control of the algorithm returns to block 1000 at
operation 1049.
[0043] FIG. 9 relates to checking patient's level of activity. At
operation 1100, the heart rate of the patient is sensed. At block
1110, a determination is made as to whether atrial arrhythmia is
occurring. If not, any applicable therapy is stopped at block 1115
and control of system 10 returns to sensing the heart rate at 1100.
If atrial arrhythmia is detected, the patient's level of activity
is sensed using an activity sensor at block 1120. A determination
is made as to the patient's heart rate at block 1130. At block
1140, a determination is made as to whether an elevated ventricular
response is present. At block 1150, if there is an elevated
ventricular response, control of the algorithm returns to block
1020. In contrast, if an elevated ventricular response is not
present, a determination is made as to whether a low ventricular
response is occurring in the patient at block 1060. A standard
pacing algorithm is implemented at block 1170 if a low ventricular
response is present. In contrast, if the patient lacks a low
ventricular response, control of the operation returns to the start
of the algorithm.
[0044] FIGS. 10A-10D represent in vivo experimental data obtained
from anesthetized animals based upon features of the claimed
invention. Specifically, this data demonstrates that local drug
delivery directly into the AVN region effectively controls
ventricular rate during AF without producing systemic effects and
toxicity. This study evaluated the effect of locally administered
acetylcholine (ACH) on AVN conduction and refractoriness properties
during sinus rhythm and AF. Canines (n=7) were anesthetized, and
instrumented to assess atrial and ventricular electrophysiology as
well as arterial blood pressure. A custom drug delivery catheter
was fixed into the AVN region using a combination of standard
electrophysiological mapping techniques and image guided therapy
via a cardiac navigation system. Its location was confirmed by
delivering an ACH test dose and resultant complete, but fully
reversible heart block in all 7 animals. As noted from data
presented below in Table 1, the duration of AV block administered
via direct AVN injection was substantially longer than for
intravenous administration of the identical dose.
TABLE-US-00001 TABLE 1 AV Block III duration and overall AV Block
duration for direct AVN Bolus injection vs. Intravenous Bolus
injection. Direct AVN Bolus Intravenous Bolus (n = 6) (n = 5)
Overall AV Block duration* (min) 41.19 .+-. 27.14 0.31 .+-. 0.43 AV
Block III duration (min) 12.30 .+-. 4.72 0.00 .+-. 0.00 *Duration
of AV block I, II and III
[0045] Subsequently, incremental doses of ACH starting at 10 ug/min
were infused into the AVN until complete atrioventricular heart
block (AVB) was observed. ACH produced AVB in a dose dependent
manner. During electrically induced AF, the ventricular rates
decreased from 182.+-.32 to 77.+-.28 beats per minutes (bpm)
(acetylcholine dosage inducing first degree AVB; p<0.05) and to
28.+-.8 bpm (third degree AVB; p<0.05) (FIG. 10A). Raw data
obtained during electrically induced AF are shown in FIG. 10B
during and without drug administration. At the first degree AVB
dose, AVN effective refractory period (ERP) at a pacing cycle
length of 400 milliseconds (msec) increased from 186.+-.37 msec to
282.+-.33 msec (p=0.06), and Wenckebach cycle length from 271.+-.29
msec to 378.+-.58 msec (p<0.05) (FIG. 10C). In addition, ACH
dose producing first AVB prolonged AV, PR and AH intervals, whereas
PP intervals, HV intervals and blood pressure remained unchanged,
demonstrating a local effect (FIG. 10D). Observed effects were
fully reversible within 20 minutes after stopping ACH infusion.
From this in vivo data, local ACH delivery into the AVN region
successfully increased AVN refractoriness and significantly
decreased ventricular rate response during electrically induced AF
in a dose related fashion. These effects occurred without
significant systemic effects and were rapidly reversible within
minutes. This may represent a novel drug delivery therapy whereby
direct AVN drug delivery is monitored and controlled to maintain an
optimal ventricular rate during AF events.
[0046] The present invention has numerous applications. For
example, while the figures relate to AF, other types of cardiac
conditions may be treated by this process. For example, AV block
may rely on the embodiment presented in FIGS. 7-9. To illustrate,
blocks 1020 and 1028 may be switched with each other. Additionally,
the blocks that describe "atrial arrhythmia" are switched to AV
block. The rest of the blocks remain unchanged. The description of
the invention is merely exemplary in nature and, thus, variations
that do not depart from the gist of the invention are intended to
be within the scope of the invention. Such variations are not to be
regarded as a departure from the spirit and scope of the
invention.
* * * * *