U.S. patent application number 15/018973 was filed with the patent office on 2016-09-08 for combined vagus-phrenic nerve stimulation device.
The applicant listed for this patent is BIOTRONIK SE & Co. KG. Invention is credited to Marcelo Baru.
Application Number | 20160256692 15/018973 |
Document ID | / |
Family ID | 55304881 |
Filed Date | 2016-09-08 |
United States Patent
Application |
20160256692 |
Kind Code |
A1 |
Baru; Marcelo |
September 8, 2016 |
COMBINED VAGUS-PHRENIC NERVE STIMULATION DEVICE
Abstract
An implantable pulse generator (IPG) includes a respiration
activity sensing unit configured to generate a signal representing
respiration activity, a stimulation unit configured to generate
nerve stimulation electric pulses, and a control unit configured to
trigger delivery of the nerve stimulation electric pulses via a
stimulation electrode on a stimulation lead connected to the
implantable pulse generator. The triggering of the stimulation
pulse delivery depends on the signal representing respiration
activity.
Inventors: |
Baru; Marcelo; (Tualatin,
OR) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
BIOTRONIK SE & Co. KG |
Berlin |
|
DE |
|
|
Family ID: |
55304881 |
Appl. No.: |
15/018973 |
Filed: |
February 9, 2016 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
62127296 |
Mar 3, 2015 |
|
|
|
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61N 1/0558 20130101;
A61B 5/4836 20130101; A61B 5/1116 20130101; A61N 1/36114 20130101;
A61B 2562/0219 20130101; A61N 1/3614 20170801; A61N 1/36514
20130101; A61B 5/0809 20130101; A61N 1/3601 20130101; A61N 1/36139
20130101; A61B 5/686 20130101; A61N 1/36053 20130101; A61N 1/3611
20130101; A61B 5/0031 20130101; A61N 1/37211 20130101; A61N 1/056
20130101; A61B 5/0826 20130101; A61N 1/3627 20130101 |
International
Class: |
A61N 1/36 20060101
A61N001/36; A61N 1/372 20060101 A61N001/372 |
Claims
1. An implantable pulse generator (106) connected or connectable to
a stimulation lead (100) having a stimulation electrode (107), the
implantable pulse generator (106) including: a. a respiration
activity sensing unit (54, 60) configured to generate a signal
representing respiration activity, b. a control unit (50)
configured to trigger delivery of nerve stimulation electrical
pulses via the stimulation electrode (107), wherein triggering of
delivery depends on the signal representing respiration
activity.
2. The implantable pulse generator (106) of claim 1 wherein the
control unit (50) is configured to: a. generate a predictive
respiration pattern from the signal representing respiration
activity, and b. trigger the stimulation pulses in dependence on
the predictive respiration pattern.
3. The implantable pulse generator (106) of claim 1: a. further
including the stimulation lead (100), wherein the stimulation lead
(100) has several stimulation electrodes (107), b. the control unit
(50) is configured to: (1) select one or more of the stimulation
electrodes (107), and (2) trigger delivery of nerve stimulation
electrical pulses via the selected electrodes (107).
4. The implantable pulse generator (106) of claim 3 wherein at
least some of the stimulation electrodes (107) are situated in a
left superior intercostal vein (101) between a phrenic nerve (103)
and a vagus nerve (104).
5. The implantable pulse generator (106) of claim 3 wherein one or
more of the stimulation electrodes (107) extend about no more than
half of the outer circumference of the stimulation lead (100).
6. The implantable pulse generator (106) of claim 1 wherein the
control unit (50) is configured to trigger delivery of nerve
stimulation electrical pulses when the signal representing
respiration activity indicates a breathing pause.
7. The implantable pulse generator (106) of claim 1 wherein the
control unit (50) is configured to trigger delivery of nerve
stimulation electrical pulses when the signal representing
respiration activity indicates decreased inspiration and expiration
amplitudes.
8. The implantable pulse generator (106) of claim 1 wherein the
signal representing respiration activity is a chest Respiration
Effort Signal (REFFS).
9. The implantable pulse generator (106) of claim 8 wherein the
respiration activity sensing unit (54): a. includes or is connected
to an accelerometer, and b. is configured to generate the chest
Respiration Effort Signal (REFFS) from a signal from the
accelerometer.
10. The implantable pulse generator (106) of claim 1 wherein the
respiration activity sensing unit (60): a. includes or is connected
to an impedance measurement unit (60) configured to generate an
impedance signal representing intrathoracic impedance, and b. is
configured to generate the chest Respiration Effort Signal (REFFS)
from the impedance signal.
11. The implantable pulse generator (106) of claim 1 further
including a telemetry unit (72) configured to: a. receive
programming, and/or b. transmit recorded data and/or status
information.
12. The implantable pulse generator (106) of claim 1 further
including a heart monitoring unit that is configured to determine
at least a heart rate.
13. The implantable pulse generator (106) of claim 1 further
including: a. a case (20) enclosing at least a portion of the
implantable pulse generator (106), wherein at least a portion of
the case is electrically conductive; b. a far-field electrogram
(ff-EGM) sensing unit (56) connected to: (1) the case (20), and (2)
a stimulation electrode (107) of the stimulation lead (100), the
far-field electrogram (ff-EGM) sensing unit (56) being configured
to sense ff-EGM (600) signals.
14. The implantable pulse generator (106) of claim 1: a. further
including the stimulation lead (100), b. wherein the stimulation
lead (100) is a multi-electrode lead configured for placement in a
left superior intercostal vein.
15. A method for nerve stimulation including the steps of: a.
sensing respiration activity, b. delivering nerve stimulation
electrical pulses via a stimulation electrode (107), wherein
delivery is dependent on the sensed respiration activity.
16. The method of claim 15: a. further including the step of
determining a predictive respiration pattern based on the sensed
respiration activity, and b. wherein the delivery of the nerve
stimulation electrical pulses is also dependent on the predictive
respiration pattern.
17. The method of claim 15 wherein the nerve stimulation electrical
pulses are delivered to a vagus nerve and/or a phrenic nerve.
18. The method of claim 15 wherein the nerve stimulation electrical
pulses are delivered during a breathing pause (504).
19. The method of claim 15 wherein: a. the nerve stimulation
electrical pulses are delivered via several stimulation electrodes
(107) on a stimulation lead (100), b. the several stimulation
electrodes (107) are situated: (1) in a left superior intercostal
vein (101), (2) between a phrenic nerve (103) and a vagus nerve
(104).
20. An implantable pulse generator (106) a. a respiration activity
sensing unit (54, 60) configured to generate a signal representing
respiration activity; b. a stimulation lead (100) having a
stimulation electrode (107) situated within a left superior
intercostal vein between a phrenic nerve (103) and a vagus nerve
(104); d. a control unit (50) configured to trigger delivery of
electric stimulation pulses via the stimulation electrode (107)
when the signal representing respiration activity indicates a
breathing pause.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority under 35 USC .sctn.119(e)
to U.S. Provisional Patent Application 62/127,296 filed 3 Mar.
2015, the entirety of which is incorporated by reference
herein.
FIELD OF THE INVENTION
[0002] The invention relates to an implantable stimulation system
suitable for vagus nerve stimulation, the system including an
implantable pulse generator (IPG) having a stimulation lead
connected to the IPG, and which has a stimulation electrode for
delivery of stimulation pulses. Preferably, the system is suitable
for Vagus-Phrenic Nerve Stimulation (VNS-PhrNS) therapy, in
particular for the treatment of patients suffering from Congestive
Heart Failure (CHF) with Central Sleep Apnea (CSA) syndrome.
BACKGROUND OF THE INVENTION
[0003] Transvascular stimulation of a vagus nerve via a catheter,
for the purpose of heart rate reduction (parasympathetic drive),
was first reported by Thompson et al. in 1998 [Thompson et al.
"Bradycardia induced by intravascular versus direct stimulation of
the vagus nerve", Annals of Thoracic Surgery, 65(3), 637-42, 1998].
A few years later, Hasdemir et al. [Hasdemir et al. "Endovascular
stimulation of autonomic neural elements in the superior vena cava
using a flexible loop catheter", Japanese Heart Journal, 44(3),
417-27, 2003] investigated the use of a flexible loop with multiple
contacts in the superior vena cava (SVC). This work showed
stimulation at anterior sites resulted in phrenic nerve
stimulation, whereas posterior site stimulation affected sinus
cycle length and atrioventricular conduction while avoiding phrenic
nerve stimulation.
[0004] Transvascular stimulation of the phrenic nerves, on the
other hand, dates back to the 1950s [Doris J. W. Escher et al.
"Clinical control of respiration by transvenous phrenic pacing",
Trans. Amer. Soc. Artif. Int. Organs, Vol. XIV, 192-197, 1968].
WO2008/092246 A1 discloses a stimulation device with a single
endovascular lead having multiple electrodes for stimulation of a
vagus nerve and/or a phrenic nerve. The reference describes phrenic
nerve stimulation to regulate breathing, and fine-tuning the
positioning of the electrode array in the internal jugular vein
(UV) by observing the patient's breathing.
[0005] U.S. Pat. No. 8,433,412 B1 discloses a lead-electrode system
for use with an Implantable Medical Device (IMD) configured to
monitor and/or treat both cardiac and respiratory conditions. More
particularly, versions of the invention relate to a lead-electrode
configuration of a combination IMD that combines therapies such as
cardiac pacing, respiratory sensing, phrenic nerve stimulation,
defibrillation, and/or biventricular pacing, referred to as Cardiac
Resynchronization Therapy (CRT). Stimulation and/or sensing leads
may be placed in a small pericardiophrenic vein, a brachiocephalic
vein, an azygos vein, a thoracic intercostal vein, or other
thoracic vein that affords proximity to the phrenic nerve for
stimulation. Respiration sensing may be performed via transthoracic
impedance.
[0006] U.S. Pat. No. 8,630,704 B2 discloses utilizing measurement
of respiratory stability or instability during sleep or rest as
feedback to control stimulation of an autonomic neural target (e.g.
vagus nerve stimulation).
[0007] Almost half of the Congestive Heart Failure (CHF) patient
population suffers from Central Sleep Apnea (CSA). Although CRT has
become the standard device therapy for the treatment of NYHA class
III or IV heart failure patients with left ventricular ejection
fractions (LVEF).ltoreq.35% and QRS.gtoreq.130 ms, only 7% of all
eligible CHF patients receive the device (see
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493802/), and
approximately 30% of those who receive it are classified as
non-responders (see
http://circ.ahajournals.org/content/117/20/2608.abstract). Hence, a
combination device as proposed by U.S. Pat. No. 8,433,412 B1 is not
optimal for the treatment of CHF with CSA.
[0008] Vagus nerve stimulation recently emerged as a potential
progression-preventing and treatment option for CHF patients.
Experimental data have demonstrated that stimulation of a vagus
nerve at the cervical level is able to reverse ventricular
remodeling of the failing heart. There is also evidence that
increasing parasympathetic activity may stimulate the production of
nitric oxide, and reduce the devastating inflammatory process
involved in heart failure. Present vagus nerve stimulation devices
for CHF involve an implanted nerve cuff electrode that connects via
wires to an IPG in the patient's chest. A standard pacemaker
sensing lead in the ventricle has been proposed in prior art for
the purpose of synchronous delivery of vagus nerve stimulation
pulses in the cardiac refractory period, although other prior art
devices operate asynchronously to the cardiac cycle. Stimulation of
both the right and left vagus nerves are disclosed in prior art for
CHF treatment.
[0009] At the cervical level, the vagus nerve bundle includes
large-diameter fibers that innervate the muscles of the larynx and
pharynx in addition to the target parasympathetic cardiac fibers.
Since the former present a lower threshold to stimulation compared
to the latter, vagus nerve stimulation therapy delivery for CHF
requires the use of special waveforms and electrode arrangements
that preferentially target the cardiac fibers. Although side
effects (e.g. coughing) are reduced with these special stimulation
techniques, they are not fully eliminated, which is a drawback of
this stimulation approach.
[0010] Transvascular stimulation of the vagus nerve cardiac
branches is very appealing, as the implantation of endovascular
leads is well known by physicians dealing with CHF patients.
Chronically implanting a lead in a large major vein as proposed by
WO2008/092246 A1 requires a suitable anchoring solution which is
not described in that reference. Unfortunately, the absence of data
supporting the safety and efficacy of SVC filters for
upper-extremity Deep Vein Thrombosis (DVT) (see
http://www.jvir.org/article/S1051-0443%2810%2900208-3/abstract)
have precluded the chronic implantation of endovascular leads in
large veins for the purpose of nerve stimulation. There is no
suitable solution in the prior art that satisfactorily addresses
this issue.
[0011] U.S. Pat. No. 8,433,412 B1 does not disclose stimulation of
the vagus nerve cardiac branches, though this is possible via a
lead in the left superior intercostal or azygos vein. In that
reference, an "implantable respiration lead" is proposed for
transvascularly stimulating a phrenic nerve. This respiration lead
may be installed in a pericardiophrenic vein, a brachiocephalic
vein, an IJV, a superior intercostal vein, the SVC, or other
appropriate locations.
SUMMARY OF THE INVENTION
[0012] The invention seeks to provide a nerve stimulation device
that advances the management/treatment of Congestive Heart Failure
(CHF) patients, in particular those who also suffer from Central
Sleep Apnea (CSA) syndrome.
[0013] The invention also seeks to provide a dual-purpose
implantable system for Vagus-Phrenic Nerve Stimulation (VNS-PhrNS)
based on a single endovascular lead and implantable pulse generator
(IPG), particularly targeting CHF patients with CSA syndrome, and
suitable for integration into a Home Monitoring/Remote Programming
therapy regime.
[0014] An exemplary version of the invention involves an IPG that
is connected or connectable to a stimulation lead having at least
one stimulation electrode. This IPG includes a respiration activity
sensing unit configured to generate a signal that represents
respiration activity (such as a chest Respiration Effort Signal
(REFFS)), and at least one stimulation unit configured to generate
electric stimulation pulses for nerve stimulation. The IPG further
includes a control unit configured to trigger delivering of
electric stimulation pulses via the stimulation electrode(s),
wherein triggering of the stimulation pulses depends on the signal
that represents respiration activity.
[0015] Preferably, the control unit is configured to generate a
predictive respiration pattern from the signal that represents
respiration activity, and to trigger the stimulation pulses
depending on the predictive respiration pattern.
[0016] Stimulation pulses can be delivered in anticipation of a
physiological event in the respiration pattern that can be
predicted from the chest Respiration Effort Signal (REFFS) or other
respiration activity signal. Preferably, the delivery of
stimulation occurs during a breathing pause period.
[0017] The control unit can be configured to trigger the
stimulation pulses using the predictive respiration pattern as
feed-forward parameter.
[0018] Preferably, the stimulation lead has several stimulation
electrodes for delivery of stimulation pulses. The control unit is
configured to select one or more of the electrodes, and to trigger
delivery of electric stimulation pulses via the selected
electrodes. This delivery may be triggered when the signal that
represents respiration activity indicates a breathing pause.
[0019] The invention reflects the view that an implantable chronic
therapy for combined CHF-CSA treatment via VNS-PhrNS should
preferably utilize a single endovascular lead that is implanted
through typical pacemaker-lead access sites (e.g. the subclavian
vein), and that avoids routing through the superior vena cava (SVC)
to allow for the possibility of implanting a Cardio Rhythm
Management (CRM) device should the patient require one in the
future. This makes the azygos vein less of a candidate, in
particular because implantable cardioverter defibrillator (ICD)
leads, for example, are also implanted in the azygos vein in
patients who present a high threshold to defibrillation stimulation
(Bar-Cohen et al. "Novel use of a vascular plug to anchor an
azygous vein ICD lead", Journal of Cardiovascular
Electrophysiology, 21(1), 99-102, 2010). The left superior
intercostal vein is then the preferred location for the placement
of this VNS-PhrNS combo lead. However, given the proximity of the
vagus branches and phrenic nerve in this location, there is a need
for a suitable therapy delivery strategy which manages stimulation
spillage.
[0020] The stimulation lead is preferably a single multi-electrode
lead that can be implanted in the left superior intercostal vein,
and which is connectable to the IPG that can be located in a pocket
in the patient's chest.
[0021] The chest Respiration Effort Signal (REFFS) is preferably
either derived by an accelerometer in the IPG, or by impedance
measurement between the IPG case and one of the lead electrodes.
Accordingly, it is preferred if the respiration activity sensing
unit includes or is connected to an accelerometer, and wherein the
respiration activity sensing unit is configured to evaluate an
accelerometer signal to generate the chest REFFS. Alternatively,
the respiration activity sensing unit can include or can be
connected to an impedance measurement unit that generates an
impedance signal that represents intrathoracic impedance, and
wherein the respiration activity sensing unit is configured to
evaluate the impedance signal to generate the chest REFFS.
[0022] The Respiration Effort Signal (REFFS) is preferably used as
feed-forward parameter for the delivery of Vagus Nerve Stimulation
(VNS) therapy so that any stimulation spillage to the phrenic nerve
will assist breathing.
[0023] The IPG is preferably connected or connectable to a
stimulation lead having several stimulation electrodes. The control
unit of the IPG is preferably configured to trigger delivery of
electric stimulation pulses via selected electrodes, wherein
triggering of the stimulation pulses depends on the chest
REFFS.
[0024] The IPG is preferably configured to perform intrathoracic
far-field electrogram (ff-EGM) recordings for CHF monitoring, and
to detect hypopnea and apnea conditions based on changes to the
chest Respiration Effort Signal (REFFS). Upon detection of one of
these conditions, Phrenic Nerve Stimulation (PhrNS) can be
delivered to restore normal breathing.
[0025] The IPG can also include a heart monitoring unit that is
configured to determine parameters such as heart rate.
[0026] The IPG may further include a ff-EGM sensing unit that is
connected to an electrically conducting case of the IPG, and to one
or more stimulation electrodes of the stimulation lead, wherein the
ff-EGM sensing unit is configured to sense and evaluate ff-EGM
signals.
[0027] The device can operate in a stimulation mode where the chest
Respiration Effort Signal (REFFS) is also used as a feed-forward
parameter for the delivery of Phrenic Nerve Stimulation (PhrNS)
therapy. This mode may minimize diaphragm atrophy if the patient is
hospitalized and placed on mechanical ventilation.
[0028] The IPG might include a telemetry unit allowing it to
communicate via a MICS-band link to an external Programmer, or to a
bedside Patient Messenger connected to a Home Monitoring/Remote
Programming Center.
[0029] The stimulation lead is preferably a percutaneous,
linear-type multi-electrode lead configured for placement in a left
superior intercostal vein. The inventors found that the left
superior intercostal vein provides a superior location for the dual
stimulation of the left phrenic nerve and the cardiac branches of
the left vagus nerve. Implantation of a lead in the left superior
intercostal vein can be done through the left subclavian vein, and
the lead can be connected to an IPG in a pocket in the left side of
the patient's chest. Several electrodes (e.g. eight, similar to a
percutaneous spinal cord lead) are preferred for easy lead
placement to achieve selective stimulation.
[0030] The invention also involves a method for nerve stimulation
including the steps of monitoring respiration activity; determining
a predictive respiration pattern based on the monitored respiration
activity; and delivering stimulation pulses depending on the
monitored respiration activity and/or the predictive respiration
pattern for delivering the stimulation pulses. The stimulation
pulses are preferably delivered to a vagus nerve and/or a phrenic
nerve. The pulse delivery preferably occurs during a breathing
pause.
[0031] Preferably, the chest Respiration Effort Signal (REFFS) is
derived by either an accelerometer in the IPG, or by impedance
measurement between an electrode in the lead and the IPG case.
[0032] Given the proximity of the nerve branches, the chest
Respiration Effort Signal (REFFS) is preferably used as a
feed-forward parameter for the delivery of Vagus Nerve Stimulation
(VNS) therapy so that any stimulation spillage to the phrenic
nerve, should it occur, is timed to assist breathing. Preferably,
VNS is delivered during the breathing pause period derived from the
chest REFFS.
[0033] The IPG may be configured so it can record the far-field
electrogram (ff-EGM) utilizing a vector between an electrode in the
lead and the IPG case. The ff-EGM can be utilized for heart rate
determination and heart condition monitoring. Preferably, the IPG
includes a ff-EGM sensing unit configured to sense and to evaluate
far-field electrogram signals, and which is connected to an
electrically-conducting area of the IPG case and to at least one
stimulation electrode of the stimulation lead.
[0034] Given apneas can occur at any time of day if the patient
falls asleep, monitoring and detection of such events is preferably
performed independently of the time of day. Preferably, the control
unit is configured to deliver Phrenic Nerve Stimulation (PhrNS)
therapy upon detection of a hypopnea or an apnea condition from the
chest Respiration Effort Signal (REFFS), i.e. shallow breathing
effort or absence of breathing effort respectively, to re-establish
normal breathing. Although the arrangement of electrodes and
stimulation technique for PhrNS will minimize spillage to the vagus
nerve (e.g. guarded cathode configuration), spillage is actually
beneficial for CHF as both are in the same frequency range.
[0035] Preferably, the IPG includes a triaxial accelerometer. The
triaxial capabilities of the accelerometer permit monitoring
sleeping positions at night time. This statistic is of particular
interest as patients with CHF generally tend to sleep in a sitting
position due to breathing difficulties (e.g., when the lungs fill
with fluid). Trend data on sleeping positions, for example, can be
utilized to analyze improvement or worsening of a patient's
condition. This trend, together with CSA event statistics and
detected heart conditions derived from the far-field electrogram
(ff-EGM) (e.g. arrhythmias), can be telemetered via a MICS-link to
a bedside Patient Messenger which is connected to a Home
Monitoring/Remote Programming Center. The same wireless link can be
used for programming of the IPG via an external Programmer.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] FIG. 1 shows an exemplary implantable stimulation
system;
[0037] FIG. 2 shows the system of FIG. 1 in combination with
external devices;
[0038] FIG. 3 is a schematic block diagram of components of an
implantable pulse generator (IPG) for use in the system of FIG. 1
or 2;
[0039] FIG. 4 is a more detailed view of the implanted
multi-electrode lead of FIG. 1 in the left superior intercostal
vein;
[0040] FIG. 5 illustrates an alternative version for the lead
wherein the four distal electrodes are implemented with opposite
active areas;
[0041] FIG. 6 illustrates a preferred stimulation arrangement for
the electrodes;
[0042] FIG. 7 illustrates that the chest Respiration Effort Signal
(REFFS) in a CHF patient with CSA alternates between two breathing
patterns; and
[0043] FIG. 8 shows that the mean power at the IPG implant sites
(i.e. somewhere between 9-a and 10-a) is 20 dB below the maximum
measured at the 11-a position (ideal chest position).
DETAILED DESCRIPTION OF EXEMPLARY VERSIONS OF THE INVENTION
[0044] FIG. 1 shows an implantable stimulation system including a
stimulation lead 100 and an implantable pulse generator (IPG) 106
with a header 22. The stimulation lead 100 is a percutaneous,
linear-type multi-electrode lead, which is implanted in the left
superior intercostal vein 101 via the subclavian vein 102 using
standard pacemaker implantation techniques. Electrodes 107 of the
lead 100 form an active contact for the delivery of stimulation
pulses and/or for impedance measurement. The stimulation lead 100
is positioned in the vein 101 so that electrodes are distributed
between the phrenic nerve 103 and the vagus nerve 104, which cross
the left superior intercostal vein 101. The lead 100 has a distal
anchoring mechanism 105, and its proximal end is routed
subcutaneously and connected to an IPG 106 implanted in the
patient's chest.
[0045] FIG. 2 illustrates a preferred system that further includes
a bedside Patient Messenger 601 and a Programmer 604, external
devices which communicate with the IPG 106. The IPG 106 can
wirelessly communicate with the Patient Messenger 601 via a
MICS-band link 602, which can further relay the information to a
Home Monitoring/Remote Programming Center. A similar link 603
allows the Programmer 604 to program the IPG 106.
[0046] FIG. 3 is a schematic diagram of some of the components of
the IPG 106. The IPG 106 includes a case (IPG case) 20 and a header
22 (see FIG. 1) for connection of the lead 100. The header 22
includes a number of connectors 24, 26, 28, 30, 32 and 34 that can
electrically connect to the connectors of the stimulation lead 100,
and thus to the electrodes 107 of the stimulation lead 100.
[0047] Within the IPG case 20, one or more stimulation units 36,
38, 40, 42, 44 and 46 are respectively electrically connected to
the connectors 24, 26, 28, 30, 32 and 34, and are configured to
generate stimulation pulses and to deliver the pulses via a
respective connector 24, 26, 28, 30, 32 and 34. However, instead of
having one stimulation unit 36 to 46 for each connector 24 to 34
(and thus for each electrode 107 of lead 100), one stimulation unit
and a switch matrix can be provided, whereby the switch matrix
allows delivery of stimulation pulses via selected connectors (and
thus via selected electrodes 107 of lead 100). In another version
of the illustrated arrangement, all electrodes 107 of lead 100 are
switched in parallel to each other, and thus only one connector and
one stimulation unit is needed.
[0048] In the version of FIG. 3, each stimulation unit 36, 38, 40,
42, 44 and 46 is connected to and controlled by a control unit 50.
The control unit 50 controls generation, and triggers delivery, of
stimulation pulses by the stimulation units 36, 38, 40, 42, 44 and
46. The stimulation pulses to be generated and triggered by each
stimulation unit 36, 38, 40, 42, 44 and 46 are tailored for vagus
and phrenic nerve stimulation.
[0049] The control unit 50 is further connected to a time signal
generator 52 that supplies a time base to the control unit 50.
[0050] The IPG 106 further includes an activity sensing unit 54,
preferably a three-axis accelerometer for sensing movements of the
IPG 106 in three spatial dimensions, which delivers an
accelerometer signal to the control unit 50.
[0051] The control unit 50 is also connected to a far-field
electrogram (ff-EGM) sensing unit 56 configured to generate a
ff-EGM signal representing a far-field electrogram 600. In order to
record such a signal, the ff-EGM sensing unit 56 is connected to at
least one of the connectors 24 to 34, and thus to one of the
electrodes 107 of lead 100. Another input of the ff-EGM sensing
unit 56 is connected to the IPG case 20. Thus, the ff-EGM sensing
unit 56 can sense voltages between an electrode 107 and the IPG
case 20 that result from electric potentials caused by the
patient's heart activity. The far-field electrogram (ff-EGM)
sensing unit 56 is configured to supply a ff-EGM signal to the
control unit 50 wherein the ff-EGM signal represents the patient's
heart activity. The patient's heart rate and other parameters can
be determined from the ff-EGM signal.
[0052] The control unit 50 is further connected to an impedance
measuring unit 60 that includes a programmable current source 62
for generating and delivering biphasic impedance measuring pulses.
The current source 62 may be electrically connected to the IPG case
20 and to at least one of the connectors 24 to 34 (and thus to at
least one of the electrodes 107 of lead 100). The impedance
measurement unit 60 further includes a voltage sensing unit 64
configured to measure a voltage difference between an electrode 107
of lead 100 and the IPG case 20, or between two electrodes 107, in
response to delivery of current pulses by the current source 62.
The current source 62 and the voltage sensing unit 64 are connected
to an impedance determination unit 66 of the impedance measurement
unit 60. The impedance determination unit 66 is configured to
generate an impedance signal depending on the voltages measured by
voltage sensing unit 64, and to supply the impedance signal to the
control unit 50. The impedance signal generated by the impedance
measurement unit 60 represents an intrathoracic impedance which
depends on the breathing activity of a patient. Thus, the control
unit 50 can determine the chest Respiration Effort Signal (REFFS)
from the impedance signal supplied by the impedance measurement
unit 60. Alternatively, as discussed below, the chest REFFS can be
determined from the accelerometer's signal supplied by the activity
sensing unit 54.
[0053] To extract the chest REFFS from the impedance signal
supplied by the impedance measurement unit 60, the control unit 50
may apply morphological operators as discussed in
[0054] U.S. Pat. No. 8,419,645 B2. U.S. Pat. No. 8,419,645 B2
describes how morphological operators can be utilized to determine
respiration parameters from a transthoracic impedance signal.
Although the measuring configuration disclosed in U.S. Pat. No.
8,419,645 B2 is different from the one described herein, and does
not utilize transthoracic impedance given the relative position of
the lead 100 with respect to the IPG 106, the method disclosed in
U.S. Pat. No. 8,419,645 B2 (particularly at column 9, line 5 to
column 10, line 26, and in FIGS. 2-5) can be applied in an
analogous manner.
[0055] The control unit 50 may be further connected to a memory
unit 70 that may serve to store signals recorded by control unit
50, and/or programs that control the operation of control unit
50.
[0056] In order to wirelessly communicate recorded signals to an
external device or to receive program instructions, a telemetry
unit 72 is also connected to the control unit 50.
[0057] FIG. 4 shows a more detailed sketch of the implanted
multi-electrode lead 100 in the left superior intercostal vein 101,
and of the crossing of the phrenic nerve 103 and the cardiac
branches 200 of the vagus nerve 104. Since the objective is to
stimulate these vagus nerve branches 200 and the phrenic nerve 103,
and both typically cross anteriorly to the vein 101, each contact
area 201 of the lead 100 preferably presents an active area 202 for
stimulation and an opposite insulated area 203 (e.g. half of a ring
contact may be coated with parylene or another insulator). The lead
100 can be rotated and implanted so the active areas 202 face the
phrenic nerve 103 and the cardiac branches 200. This minimizes
unwanted stimulation of the laryngeal nerve branches 204, which
form part of the vagus nerve 104 near the vein 101 crossing. The
anchoring mechanism 105 of the lead 100 may utilize elastic loops
205 similar to those employed in embolic protection devices.
[0058] FIG. 5 illustrates an alternative version of the lead 100
wherein the contact areas 201 of four distal electrodes 107 are
each implemented with opposing active areas 202 separated by
insulating areas 203. In yet another alternative version for the
lead 100, the four distal electrodes 107 each include three active
areas 202 separated by insulating areas 203. These alternative lead
designs allow for improved stimulation selectivity of the cardiac
branches 200 due to anatomical variations that may occur in the
branching from the main vagus nerve trunk 104.
[0059] FIG. 6 illustrates a preferred stimulation arrangement for
the electrodes 107. A first group 400 of electrodes 107 implements
a guarded-cathode configuration for the stimulation of the phrenic
nerve 103 whereas a second group 401 of electrodes 107 does the
same for the stimulation of the vagus nerve cardiac branches 200.
The stimulation is preferably current-based and is not delivered
simultaneously, i.e. Vagus Nerve Stimulation (VNS) is delivered
during normal breathing (as discussed below), and is interrupted
when hypopnea 506 or apnea events 507 (see FIG. 7) are detected
from the chest Respiration Effort Signal (REFFS).
[0060] FIG. 7 illustrates that the chest REFFS in a CHF patient
with CSA alternates between two breathing patterns. The top pattern
500 represents normal breathing, whereas the bottom 501, known as
the Cheyne-Stokes respiration pattern, is typically observed at
sleep.
[0061] The chest REFFS Amplitude can be proportional to
gravitational acceleration (.varies.g) if an accelerometer in the
IPG 106 is used, or proportional to ohms (.OMEGA.) if impedance
measurement between the IPG's case 20 and an electrode 107 in the
lead 100 is utilized instead. Normal breathing alternates periods
of inspiration 502 and expiration 503, with a breathe pause 504 in
between, and with a minimum REFFS peak-to-peak amplitude 505
indicative of the patient's normal tidal volume.
[0062] The chest REFFS may be obtained by first band-pass filtering
the accelerometer or impedance signal between 0.1 Hz and 0.5 Hz.
FIG. 8 (which is adapted from Rendon et al. "Mapping the Human Body
for Vibrations using an Accelerometer", Proceedings of the 29th
Annual IEEE EMBS International Conference, FrA06.1, pp. 1671-4,
2007) shows that the mean power at the IPG 106 implant sites (i.e.
somewhere around 9-a and 10-a) is 20 dB below the maximum measured
at the 11-a position (ideal chest position). Hence, signal
processing for extraction of the chest REFFS may involve a
morphological filter algorithm given the reduced signal-to-noise
ratio. In an alternative version, signal processing for extraction
of the chest REFFS is based on discrete wavelet transforms. In this
case, combining signals from both the accelerometer signal supplied
by the activity sensing unit 54 and the far-field electrogram
(ff-EGM) 600 may increase the accuracy of event classification
compared to use of only the accelerometer signal.
[0063] Vagus Nerve Stimulation (VNS) therapy preferably consists of
a programmable train of one or more pulses with a fixed charge per
pulse, and a fixed frequency between them, delivered in
anticipation of a physiological event in the respiration pattern
that can be predicted from the chest Respiration Effort Signal
(REFFS). In a preferred version, the beginning of the delivery of
the VNS train of pulses occurs during the breathing pause period
504. Given the delay between Phrenic Nerve Stimulation (PhrNS) and
contraction of the diaphragm muscle, this feed-forward control
permits any VNS stimulation spillage to the phrenic nerve (should
it occur) to appear at the inspiration period 502, thereby
providing breathing assistance for the patient. VNS may be duty
cycled and delivered intermittently, i.e. once every "n" breathing
pause periods 504, and might only be active during pre-programmed
daily sessions.
[0064] When the chest REFFS amplitude 505 drops, a hypopnea event
506 may be declared by a detection algorithm in the IPG 106, and
PhrNS therapy may be started during the next breathing pause period
504. To directly detect the initiation of apnea events 507, a
programmable timer 508 from the onset of each inspiration period
502 (normal breathing 500 established) allows starting PhrNS
therapy if the following onset of inspiration period 502 cannot be
derived from the chest REFFS before the timer 508 elapses.
[0065] Vagus Nerve Stimulation (VNS) and Phrenic Nerve Stimulation
(PhrNS) are preferably delivered multiplexed in time, and PhrNS has
priority over VNS, i.e. if VNS is being delivered and either a
hypopnea 506 or an apnea 507 condition is detected from the chest
REFFS, then VNS may be aborted until PhrNS restores normal
breathing 500.
[0066] Phrenic Nerve Stimulation (PhrNS) therapy preferably
consists of a programmable train of pulses of similar frequency
compared to VNS (tens of Hz). However, each train may include a
ramp up phase, both in charge injected per pulse and in frequency
between pulses, and a ramp down phase. This type of train allows
for a more natural recruitment of the diaphragm. Once PhrNS
successfully assists restoration of the chest REFFS to the
peak-to-peak amplitude 505, the stimulation is stopped (and the
chest REFFS monitoring is continued).
[0067] The IPG 106 might operate in a stimulation mode where the
chest Respiration Effort Signal (REFFS) is also used as
feed-forward parameter for the delivery of Phrenic Nerve
Stimulation (PhrNS) therapy. This mode might be triggered by the
patient or clinician (as by placing a magnet near the IPG 106) if,
for example, the patient is hospitalized and placed on mechanical
ventilation. Phrenic Nerve Stimulation (PhrNS) may minimize
diaphragm atrophy, and may therefore accelerate the period during
which the patient is weaned off ventilation. This mode does not
prevent Vagus Nerve Stimulation (VNS) therapy from being delivered,
as it can be time-multiplexed with PhrNS.
[0068] The triaxial accelerometer might also be used to extract
sleeping position patterns. For example, a decrease in the patient
sleeping angle may indicate improvement of the patient's condition,
as patients with CHF tend to sleep with several pillows due to
breathing difficulties associated with the disease (owing to the
lungs filling with fluid).
[0069] Returning to FIG. 2, the far-field electrogram (ff-EGM) 600
is recorded between an electrode 107 in the lead 100 and the IPG's
case 20. Diagnostics and statistics such as sleeping angles, apnea
events, arrhythmias, etc. can be wirelessly communicated to the
bedside Patient Messenger 601 via a MICS-band link 602, which can
further relay the information to a Home Monitoring/Remote
Programming Center. A similar link 603 allows a Programmer 604 to
program the IPG 106.
[0070] A few of the advantages achieved by the invention are:
[0071] 1) only a single endovascular lead for dual Vagus-Phrenic
Nerve Stimulation is needed, with reduced side effects;
[0072] 2) the system is implantable via standard pacemaker
techniques and tools, thereby reducing risk and physician training
requirements;
[0073] 3) the system avoids leads through the SVC/heart chambers,
and is therefore compatible with other CRM devices;
[0074] 4) the system can provide assistive breathing therapy for
CHF patients admitted to the hospital and placed on mechanical
ventilation;
[0075] 5) the system offers added diagnostics/statistics for CHF
patients suffering from CSA; and
[0076] 6) the system provides improved therapy for CHF patients
suffering from CSA.
[0077] It is emphasized that the foregoing versions of the
invention are merely exemplary, and they can be modified in various
respects. In particular, it is possible for IPG 106 to utilize
alternative methods of stimulation, e.g., voltage-based
stimulation. It is also possible for the lead 100 to include
additional electrodes 107 that are situated in the access vein when
the lead 100 is implanted as described above. Such additional
electrodes may also permit stimulating the vagus and phrenic nerves
transvascularly through the access vein's wall. This feature may
further improve stimulation selectivity. This invention can readily
be adapted to a number of different kinds of nerve stimulation
devices and nerve stimulation methods by use of the concepts
discussed herein.
[0078] The invention is not intended to be limited to the exemplary
versions discussed above, but rather is intended to be limited only
by the claims set out below. Thus, the invention encompasses all
different versions that fall literally or equivalently within the
scope of these claims.
* * * * *
References