US20160256692A1

US20160256692A1 - Combined vagus-phrenic nerve stimulation device

Info

Publication number: US20160256692A1
Application number: US15/018,973
Authority: US
Inventors: Marcelo Baru
Original assignee: Biotronik SE and Co KG
Current assignee: Biotronik SE and Co KG
Priority date: 2015-03-03
Filing date: 2016-02-09
Publication date: 2016-09-08
Also published as: US20160256687A1; EP3064131A1; US10143844B2

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.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority under 35 USC §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

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

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.
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.
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.
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).
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)≦35% and QRS≧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.
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.
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.
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.
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

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.
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.
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.
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.
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.
The control unit can be configured to trigger the stimulation pulses using the predictive respiration pattern as feed-forward parameter.
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.
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.
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.
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.
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.
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.
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.
The IPG can also include a heart monitoring unit that is configured to determine parameters such as heart rate.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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

FIG. 1 shows an exemplary implantable stimulation system;

FIG. 2 shows the system of FIG. 1 in combination with external devices;

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;

FIG. 4 is a more detailed view of the implanted multi-electrode lead of FIG. 1 in the left superior intercostal vein;

FIG. 5 illustrates an alternative version for the lead wherein the four distal electrodes are implemented with opposite active areas;

FIG. 6 illustrates a preferred stimulation arrangement for the electrodes;

FIG. 7 illustrates that the chest Respiration Effort Signal (REFFS) in a CHF patient with CSA alternates between two breathing patterns; and

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

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.
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.
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.
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.
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.
The control unit 50 is further connected to a time signal generator 52 that supplies a time base to the control unit 50.
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.
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.
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.
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
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.
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.
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.
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.
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.
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).
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.
The chest REFFS Amplitude can be proportional to gravitational acceleration (∝g) if an accelerometer in the IPG 106 is used, or proportional to ohms (Ω) 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.
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.
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.
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.
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.
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).
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.
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).
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.
A few of the advantages achieved by the invention are:
1) only a single endovascular lead for dual Vagus-Phrenic Nerve Stimulation is needed, with reduced side effects;
2) the system is implantable via standard pacemaker techniques and tools, thereby reducing risk and physician training requirements;
3) the system avoids leads through the SVC/heart chambers, and is therefore compatible with other CRM devices;
4) the system can provide assistive breathing therapy for CHF patients admitted to the hospital and placed on mechanical ventilation;
5) the system offers added diagnostics/statistics for CHF patients suffering from CSA; and
6) the system provides improved therapy for CHF patients suffering from CSA.
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.
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.

Claims

What is claimed is:

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.