JP4755111B2 - Baroreflex stimulation system - Google Patents

Description

  The present application relates generally to implantable medical devices, and in particular to systems, devices, and methods for reducing hypertension using baroreceptor stimulation.

  It is known to implant electrical stimulators on a long-term basis, such as cardiac stimulators, for administering medical treatment. Examples of cardiac stimulators include implantable cardiac rhythm management (CRM) devices such as pacemakers, implantable defibrillators (ICDs), and implantable devices that can perform pacing and defibrillation functions. .

  A CRM device is an implantable device that provides electrical stimulation to a selected heart chamber to treat a disorder of cardiac rhythm. For example, an implantable pacemaker is a CRM device that paces the heart with pacing pulses in tune. If functioning properly, the pacemaker makes up for the heart itself not being paced with the proper rhythm to meet metabolic demands by increasing the minimum heart rate. Some CRM devices synchronize pacing pulses delivered to different areas of the heart to regulate contraction. The coordinated contraction allows the heart to pump effectively while providing sufficient cardiac output.

  Heart failure refers to a clinical syndrome that causes subnormal cardiac output in which heart function falls below levels appropriate to meet the metabolic demands of peripheral tissues. Heart failure may manifest as congestive heart failure (CHF) due to concomitant veins or pulmonary congestion. Heart failure is caused by a variety of etiologies such as ischemic heart disease.

  Hypertension is a cause of heart disease and other related heart comorbidities. When blood vessels narrow, hypertension occurs. As a result, the heart works hard to maintain flow at higher blood pressure, which contributes to heart failure. Many people in the general population suffer from hypertension, as well as many patients with implanted pacemakers or defibrillators. If blood pressure and hypertension can be reduced, they can improve not only long-term mortality but also the quality of survival. Many patients who suffer from hypertension do not respond well to treatment, such as lifestyle changes or treatments related to antihypertensive agents.

  The baroreceptive region or field can sense pressure changes, such as changes in blood pressure. The baroreceptive region is referred to herein as a baroreceptor and generally includes some sensor of pressure change. For example, baroreceptors contain afferent nerves and also function as central reflex receptors that result from increased blood pressure from the inside and tend to decrease blood pressure, and include sensory nerve endings that are sensitive to wall spread . Baroreflex functions as a negative feedback system and is associated with a reflex mechanism triggered by baroreceptor stimulation. The increase in pressure widens the blood vessel, which in turn activates baroreceptors within the blood vessel. Baroreceptor activation occurs spontaneously via internal pressure and arterial wall spread, resulting in baroreflex inhibition of sympathetic nerve activity (SNA) and a reduction in systemic blood pressure. Increased baroreceptor activity induces SNA reduction, which reduces blood pressure by reducing peripheral vascular resistance.

  The general concept of stimulating afferent nerve trunks derived from baroreceptors is known. For example, direct electrical stimulation is applied to the vagus nerve and carotid sinus. Studies have shown that electrical stimulation of the carotid sinus nerve leads to a reduction in experimental hypertension, and that direct electrical stimulation to the baroreceptor region of the carotid sinus itself causes a reduction in the reflex of experimental hypertension .

  Electrical systems are proposed to treat hypertension in patients who do not otherwise respond favorably to treatment with lifestyle changes or antihypertensive agents, and possibly to reduce drug dependence in other patients It was done.

  Various aspects and embodiments of the present subject matter apply baroreflex therapy, sense physiological parameters indicative of the effectiveness of baroreflex therapy, and modify baroreflex therapy based on the physiological parameters. And a method comprising: Applying baroreflex therapy includes electrically stimulating the baroreceptor region in or near the heart using a lead that is intravascularly supplied to at least a portion of the heart.

  Various aspects and embodiments of the present subject matter provide baroreflex therapy to a baroreceptor region near the heart via a lead supplied intravascularly via at least a portion of the heart to suppress sympathetic activity. An implantable baroreflex stimulator is provided that includes means and means for providing feedback regarding the effectiveness of the baroreflex therapy used to control the performance of the baroreflex therapy. According to various embodiments, the implantable stimulator includes a pulse generator, a lead, a sensor, and a controller. The pulse generator generates a baroreflex stimulation signal as part of the baroreflex treatment. The lead is electrically connected to the pulse generator and is configured to be delivered intravascularly to the heart. The lead includes an electrode positioned in or near the heart to send a baroreflex signal to the baroreceptor region in or near the heart. The sensor senses a physiological parameter related to the effectiveness of the baroreflex treatment and provides a signal indicative of the effectiveness of the baroreflex treatment. A controller is connected to the pulse generator to control the baroreflex stimulation signal and to a sensor to receive a signal indicating the effectiveness of the baroreflex treatment.

  This summary is an overview of some of the teachings of the present application and is not intended to be an exclusive or comprehensive treatment of the present subject matter. Further details about the present subject matter are found in the detailed description and appended claims. Other aspects will become apparent to those skilled in the art upon reading and understanding the following detailed description and viewing the drawings that form a part thereof, each of which is not to be construed in a limiting sense. Let's go. The scope of the present invention is defined by the appended claims and their equivalents.

  The following detailed description of the subject matter refers to the accompanying drawings that illustrate, by way of illustration, specific aspects and embodiments in which the subject matter is implemented. These embodiments are described in sufficient detail to enable those skilled in the art to practice the present subject matter. Other embodiments may be utilized and structural, logical, and electrical changes may be made without departing from the scope of the present subject matter. References to “an”, “one” or “various” embodiments in this disclosure are not necessarily directed to the same embodiment, and such references are intended to one or more embodiments. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope is defined only by the appended claims and the full scope of legal equivalents to which such claims are entitled. The

Hypertension and Baroreflex Physiology To assist the reader in understanding the present disclosure, a brief discussion of physiology regarding hypertension and baroreceptors is provided. This brief discussion introduces hypertension, autonomic nervous system and baroreflex.

  Hypertension is a cause of heart disease and other related heart comorbidities. Hypertension is generally associated with high blood pressure, such as a transient or sustained increase in systemic blood pressure to a level that is prone to trigger cardiovascular injury or other adverse consequences. Hypertension was exclusively defined as systolic blood pressure above about 140 mmHg or diastolic blood pressure above about 90 mmHg. Hypertension occurs when the blood vessels narrow. As a result, the heart works busy to maintain flow at higher blood pressure. Uncontrolled hypertension results include, but are not limited to, retinal vascular disease and stroke, left ventricular hypertrophy and failure, myocardial infarction, dissecting aneurysm, and renal vascular disease.

  The autonomic nervous system (ANS) regulates “involuntary” organs, while the contraction of voluntary (skeletal) muscles is controlled by somatic motor nerves. Examples of involuntary organs include breathing and digestive organs, and also include blood vessels and the heart. Often, the ANS functions involuntarily and reflexly to regulate glands, regulate skin, eye, stomach, intestine, bladder muscles, and for example, muscles around the heart muscle and blood vessels.

  ANS includes, but is not limited to, the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system is closely related to the “fight or escape response” to stress and emergencies. Among other effects, “fight or runaway response” increases blood pressure and heart rate to increase skeletal muscle blood flow, and reduces digestion to provide energy for “fight or runaway” Let The parasympathetic nervous system is closely related to relaxation and “rest and digestive response”, which, among other effects, reduces blood pressure and heart rate and increases digestion to conserve energy. The ANS maintains normal internal function and cooperates with the somatic nervous system.

  The subject matter of this disclosure generally refers to the effects that ANS has on heart rate and blood pressure, including vasodilation and stenosis. Heart rate and power increase when the sympathetic nervous system is stimulated and decrease when the sympathetic nervous system is suppressed (parasympathetic nervous system is stimulated). 1A and 1B show the neural mechanism of peripheral vascular control. FIG. 1A generally shows afferent nerves to the vasomotor center. The afferent nerve transmits an impulse toward the nerve center. The vasomotor center relates to the nerves that cause the blood vessels to expand and contract in order to control the dimensions of the blood vessels. FIG. 1B generally shows the efferent nerve from the vasomotor center. Centrifugal nerves transmit impulses avoiding nerve centers.

  Stimulating the sympathetic and parasympathetic nervous systems has effects other than heart rate and blood pressure. For example, stimulating the sympathetic nervous system dilates the pupil, reduces saliva and mucus production, relaxes bronchial muscles, reduces the continuous wave of involuntary contraction (peristalsis) and gastric motility, Increases the conversion of glycogen to glucose by the liver, decreases urinary secretion by the kidneys, relaxes the walls, and closes the sphincter of the bladder. Stimulating the parasympathetic nervous system (suppressing the sympathetic nervous system) contracts the pupil, increases saliva and mucus production, contracts bronchial muscles, increases secretion and motility in the stomach and large intestine, And increases digestion in the small intestine, increases urine secretion, contracts the wall, and relaxes the sphincter of the bladder. The functions associated with the sympathetic and parasympathetic nervous systems are many and are complexly integrated with each other. Thus, in order to achieve a desired response, such as vasodilation in one physiological system, promiscuous stimulation of the sympathetic and / or parasympathetic nervous system also results in an undesirable response in other physiological systems.

  A baroreflex is a reflex caused by stimulation of a baroreceptor. Baroreceptors are the result of increased pressure from the inside and act as receptors for central reflex mechanisms that tend to reduce the pressure, and are sensitive to wall stretching, atrial appendages, cardiac fat pads, vena cava, aorta Includes any sensor of pressure change, such as the arch, sensory nerve endings in the carotid sinus wall. In addition, baroreceptors include afferent nerve trunks such as vagus, aorta, and carotid nerves leading from sensory nerve endings. Stimulating baroreceptors reduces systemic blood pressure by suppressing sympathetic activity (stimulating the parasympathetic nervous system) and reducing peripheral vascular tolerance and cardiac contractility. Baroreceptors are naturally stimulated by internal pressure and by stretching the arterial wall.

  Some aspects of this summary reduce the undesirable effects of indiscriminate stimulation of the nervous system and rather than stimulate the afferent nerve trunk for the purpose of stimulating the desired response (eg, reducing hypertension) Stimulates specific nerve endings in the arterial wall locally. For example, some embodiments stimulate baroreceptor sites within the pulmonary artery. Some embodiments of the present invention involve stimulation of nerve endings in the baroreceptor site or aorta, heart chambers, cardiac fat pad, and in some embodiments of the present summary, afferents such as vagus, carotid, and aortic nerves. It involves stimulating the nerve trunk. In some embodiments, cuff electrodes are used to stimulate the afferent nerve trunk, and in some embodiments, in order to stimulate the afferent nerve trunk, electrical stimulation is passed through the vessel wall in the vessel near the nerve. Stimulate the afferent nerve trunk using an intravascular lead positioned at the

  2A-2C show the heart. As shown in FIG. 2A, heart 201 includes superior vena cava 202, aortic arch 203, pulmonary artery 204, and is useful for providing a contextual relationship with the description of FIGS. 3-5. As discussed in more detail below, pulmonary artery 204 includes a baroreceptor. The lead, like the cardiac pacemaker lead, passes through the peripheral vein, through the tricuspid valve, is inserted into the right ventricle of the heart (not shown in the figure), and is inserted into the blood vessel from the right ventricle through the pulmonary valve. It extends to. A part of the pulmonary artery and the aorta are close to each other. Various embodiments stimulate baroreceptors in the aorta using leads positioned in the pulmonary artery. Thus, according to various aspects of the present subject matter, baroreflex is stimulated in or around the pulmonary artery by at least one electrode inserted intravascularly into the pulmonary artery. Alternatively, a wireless stimulator with or without pressure sensing capability is positioned through the catheter in the pulmonary artery. Stimulation and / or control of energy for stimulation is provided by another implantable or external device via ultrasound, electromagnetic or a combination thereof. Aspects of the present subject matter provide a relatively non-invasive surgical technique for implanting baroreceptor stimulators into pulmonary arteries in blood vessels.

  FIGS. 2B-2C further illustrate a cardiac fat pad with nerve endings that show the right and left sides of the heart, respectively, and function as baroreceptor sites. FIG. 2B shows right atrium 267, right ventricle 268, sinoatrial node 269, superior vena cava 202, inferior vena cava 270, aorta 271, right pulmonary vein 272, and right pulmonary artery 273. FIG. 2B also shows a cardiac fat pad 274 between the superior vena cava and the aorta. Baroreceptor nerve endings in cardiac fat pad 274 are stimulated in some embodiments using electrodes fixed to the fat pad, and in some embodiments, for example, the right pulmonary artery or superior vena cava Intravascularly stimulated using an intravascularly supplied lead positioned in the vicinity of the fat pad. 2C shows left atrium 275, left ventricle 276, right atrium 267, right ventricle 268, superior vena cava 202, inferior vena cava 270, aorta 271, right pulmonary vein 272, left pulmonary vein 277, right pulmonary artery 273, coronary sinus. 278 is shown. FIG. 2C also shows a cardiac fat pad 279 located near the right cardiac vein and a cardiac fat pad 280 located near the inferior vena cava and the left atrium. Baroreceptor nerve endings within fat body 279 are stimulated in some embodiments using electrodes secured to fat body 279, and in some embodiments, eg, right pulmonary artery 273 or right pulmonary vein 272. Stimulated using an intravascularly delivered lead positioned in the vicinity of the fat pad within the blood vessel. The baroreceptors in 280 are stimulated in some embodiments using electrodes fixed to the fat pad, and in some embodiments, intravascular such as the inferior vena cava 270 or coronary sinus. And stimulated using an intravascularly delivered lead positioned in the vicinity of the fat pad or a lead in the left atrium 275.

  FIG. 3 shows baroreceptors in the areas of carotid sinus 305, aortic arch 303, and pulmonary artery 304. Aortic arch 303 and pulmonary artery 304 were previously described with respect to the heart of FIG. 2A. As shown in FIG. 3, the vagus nerve 306 provides a sensory nerve ending 307 that extends and functions as a baroreceptor in the aortic arch 303, the carotid sinus 305, and the common carotid artery 310. The glossopharyngeal nerve 308 provides a nerve ending 309 that functions as a baroreceptor within the carotid sinus 305. For example, nerve endings 307 and 309 are sensitive to wall stretching resulting from increased pressure from the inside. Activation of these nerve endings reduces pressure. Although not shown in the figure, the fat pad and heart atrium and ventricle also contain baroreceptors. The cuff is placed around the afferent nerve trunk, such as the vagus nerve that leads from the baroreceptor to the vasomotor center to stimulate the baroreflex. According to various embodiments of the present subject matter, the afferent nerve trunk is stimulated using a cuff positioned in a blood vessel in the vicinity of the afferent nerve or an intravascularly supplied lead.

  FIG. 4 shows baroreceptors in and around the pulmonary artery 404. The superior vena cava 402 and aortic arch 403 are also shown. As shown, pulmonary artery 404 includes a number of baroreceptors 411, as generally indicated by dark areas. In addition, closely spaced baroreceptors are located near the arterial chord attachment 412. FIG. 4 also shows the right ventricle 413 of the heart and the pulmonary valve 414 that separates the right ventricle 413 from the pulmonary artery 404. According to various embodiments of the present subject matter, the lead is inserted through the peripheral vein, passed through the tricuspid valve, into the right ventricle, and right to stimulate baroreceptors in and / or around the pulmonary artery. The ventricle 413 is passed through the pulmonary artery valve 414 to the pulmonary artery 404. In various embodiments, for example, the lead is positioned to stimulate baroreceptors near the arterial chord 412. FIG. 5 shows baroreceptor field 512 in pulmonary trunk 504 and aortic arch 503 near the arterial duct. Some embodiments position a lead in the pulmonary artery to stimulate baroreceptor sites in the aorta and / or fat body, as shown in FIGS. 2B-2C.

  FIG. 6 shows a known relationship between respiration 615 and blood pressure 616 when the left aortic nerve is stimulated. When the nerve is stimulated with 617, blood pressure 616 drops and respiration 615 becomes faster and deeper as indicated by the higher frequency and amplitude of the respiration waveform. Respiration and blood pressure appear to return to the pre-stimulus state approximately 1-2 minutes after the stimulus is removed. Various embodiments of the present subject matter use this relationship between respiration and blood pressure by using respiration as a surrogate parameter for blood pressure.

  FIG. 7 shows the known blood pressure response to carotid nerve stimulation in hypertensive dogs during 6 months of intermittent carotid nerve stimulation. The figure shows that the blood pressure of the stimulated dog 718 is significantly lower than that of a control dog 719 that also has high blood pressure. Thus, intermittent stimulation can cause a baroreflex that reduces hypertension.

Baroreflex Stimulator System Various embodiments of the present subject matter relate to a baroreflex stimulator system. Such baroreflex stimulation systems are also referred to herein as neural stimulation (NS) devices or NS sections. Examples of neural stimulators include an anti-hypertension (AHT) device, or AHT section, used to treat hypertension. Various embodiments of the present subject matter include a stand-alone implantable baroreflex stimulator system, including an implantable device integrating an NS and cardiac rhythm management (CRM) unit, and connecting the implantable device wirelessly or A system having at least one embedded NS device and an embedded CRM device capable of communicating with each other via leads. Integrating NS and CRM functions performed within the same or separate devices improves these therapeutic aspects by allowing NS and heart therapies to work together intelligently.

  FIG. 8 illustrates a system 820 that includes an implantable medical device (IMD) 821 and a programmer 822 in accordance with various embodiments of the present subject matter. Various embodiments of the IMD 821 include only neurostimulator functions, and various embodiments include a combination of NS and CRM functions. Some embodiments of the neural stimulator provide AHT function. The programmer 822 and the IMD 821 can communicate data and instructions wirelessly. In various embodiments, for example, programmer 822 and IMD 821 use telemetry coils to communicate data and instructions wirelessly. Thus, the programmer is used to coordinate the programmed therapy provided by the IMD 821, and the IMD uses device data (such as battery and lead resistance) and sensing (using wireless telemetry, for example). And report treatment data (such as stimulus data) to the programmer. According to various embodiments, the IMD 821 stimulates baroreceptors to provide NS therapy, such as AHT therapy. Various embodiments of the IMD 821 stimulate baroreceptors within the pulmonary artery using a lead delivered through the right ventricle and further delivered to the pulmonary artery, similar to a cardiac pacemaker lead. According to various embodiments, the IMD 821 includes a sensor that senses ANS activity. Such a sensor can be used to provide feedback in a closed loop control system. For example, various embodiments sense surrogate parameters such as respiration and blood pressure indicative of ANS activity. According to various embodiments, the IMD further includes cardiac stimulation capabilities, such as pacing and defibrillation capabilities, in addition to the ability to stimulate baroreceptors and / or sense ANS activity.

  FIG. 9 illustrates an implantable medical device (IMD) 921 such as the IMD 821 shown in the system 820 of FIG. 8, according to various embodiments of the present subject matter. The illustrated IMD 921 performs an NS function. Some embodiments of the IMD 921 shown perform AHT functions and thus describe an implantable AHT device. The illustrated device 921 includes a control circuit 923 and a memory 924. The control circuit 923 can be implemented using hardware, software, and a combination of hardware and software. For example, according to various embodiments, control circuit 923 includes a processor that executes instructions recorded in memory 924 that perform functions associated with NS therapy, such as AHT therapy. For example, the illustrated device 921 further includes a transceiver 925 and associated circuitry used to communicate with a programmer or other external or internal device. Various embodiments have wireless communication capabilities. For example, some transceiver embodiments use a telemetry coil to communicate wirelessly with a programmer or other external or internal device.

  The illustrated device 921 further includes a baroreceptor stimulation circuit 926. Various embodiments of the device 921 also include a sensor circuit 927. One or more leads are connected to sensor circuit 927 and baroreceptor stimulation circuit 926. The baroreceptor stimulation circuit 926 is used to apply an electrical stimulation pulse to a desired baroreceptor, such as a baroreceptor site in the pulmonary artery, via one or more stimulation electrodes. The sensor circuit 927 is used to detect and process surrogate parameters, such as blood pressure, respiration, etc. to determine ANS neural activity and / or ANS activity.

  According to various embodiments, the stimulation circuit 926 may include any one of the following pulse characteristics: stimulation pulse amplitude 928, stimulation pulse frequency 929, pulse burst frequency 930 or duty cycle, pulse waveform 931, Or a module for setting two or more combinations is included. Examples of wave forms include waves with the desired harmonic components to mimic white noise, such as square, triangular, sine waves as well as spontaneous baroreflex stimulation.

  10A-10C illustrate baroreceptor stimulation leads with integrated pressure sensors (IPS) according to various embodiments of the present subject matter. Although not drawn to scale, these illustrated leads 1032A, 1032B, 1032C include an IPS 1033 having baroreceptor stimulation electrodes 1034 for observing changes in blood pressure and hence the effects of baroreceptor stimulation. These lead illustrations should not be read as limiting other aspects or embodiments of the present subject matter. In various embodiments, for example, micro electrical mechanism system (MEMS) technology is used to sense blood pressure. Some sensor embodiments determine blood pressure based on the displacement of the membrane.

  10A-10C show IPS on the leads. Some embodiments embed IPS within an IMD or NS device. The stimulator and sensor functions can be integrated even if the stimulator and sensor functions are located on separate leads or locations.

  The lead 1032A shown in FIG. 10A includes a baroreceptor stimulation electrode 1034 and an IPS 1033 positioned distally. This lead may be used to stimulate baroreceptor sites, such as, for example, pulmonary arteries, aortic arches, arterial chords, coronary sinus sites in the atria and ventricular cavities and / or in the cardiac fat body. Intravascular introduction is possible.

  A lead 1032B shown in FIG. 10B includes a tip electrode 1035, a first ring electrode 1036, a second ring electrode 1034, and an IPS 1033. The lead can be inserted into or near the heart chamber and at least some of the electrodes 1035, 1036, 1034 can be used to pace or otherwise stimulate the heart and At least some are further positioned proximate to the baroreceptor site so that at least one baroreceptor site can be stimulated. IPS 1033 is used to sense blood pressure. In various embodiments, IPS is used to sense blood pressure in a blood vessel near the baroreceptor site selected for stimulation.

  The lead 1032C shown in FIG. 10C includes a baroreceptor stimulation electrode 1034, an IPS 1033, and a ring electrode 1036 positioned distally. This lead 1032C is inserted into the blood vessel, for example, into the right atrium and ventricle and then through the pulmonary valve and into the pulmonary artery. Depending on the programming within the device, electrode 1036 can be used to regulate and / or sense cardiac activity, such as can occur in the right ventricle, and electrode 1034 and IPS 1033 can utilize baroreflex activity via surrogate parameters. It is located near baroreceptors in or near the pulmonary artery to stimulate and sense directly or indirectly.

  Accordingly, various embodiments of the present subject matter provide an implantable NS device that automatically adjusts baroreceptor stimulation using IPS. Integrating the pressure sensor into the lead provides localized feedback regarding the stimulus. This localized sensing improves feedback control. For example, an integrated sensor can be used to compensate for baroreflex inertia so that the target is not continuously removed. According to various embodiments, the device observes pressure parameters such as mean arterial pressure, systolic pressure, diastolic pressure, and the like. When the mean arterial pressure increases or remains greater than the programmable target pressure, for example, the device stimulates the baroreceptor at an increased rate to reduce blood pressure and control hypertension. As the mean arterial pressure decreases towards the target pressure, the device responds by reducing baroreceptor stimulation. In various embodiments, the algorithm takes into account the current metabolic state (cardiac demand) and adjusts neural stimulation accordingly. An NS device with IPS can automatically adjust baroreceptor stimulation to which the implantable NS device determines the patient's hypertension level and responds by sending the appropriate level of therapy. However, it should be noted that other sensors can be used to provide closed loop feedback control, including NS or sensors that are not present in the neurostimulator.

  FIG. 11 shows an implantable medical device (IMD) 1121 as shown at 821 in FIG. 8 having an anti-hypertension (AHT) portion 1137 and a cardiac rhythm management (CRM) portion 1138 according to various embodiments of the present subject matter. Indicates. The illustrated device 1121 includes a controller 1123 and a memory 1124. According to various embodiments, the controller 1123 includes hardware, software, or a combination of hardware and software to perform baroreceptor stimulation and CRM functions. For example, the programmed therapy application discussed in this disclosure can be stored as computer-readable instructions embodied in memory and executed by a processor. According to various embodiments, the controller 1123 includes a processor that executes instructions recorded in memory to perform baroreceptor stimulation and CRM functions. The illustrated device 1121 further includes a transceiver 1125 and associated circuitry for use to communicate with a programmer or other external or internal device. Various embodiments include a telemetry coil.

  The CRM treatment unit 1138 includes members for stimulating the heart and / or sensing cardiac signals using one or more electrodes, i.e., members based on management of the controller. The CRM treatment unit includes a pulse generator 1139 that is used to provide an electrical signal through the electrodes to stimulate the heart and includes a sensing circuit 1140 for detecting and processing the sensed cardiac signal. In addition. Interface 1141 is typically used by controller 1123 to communicate between pulse generator 1139 and sensing circuit 1140. Three electrodes are shown as an example of use to provide CRM therapy. However, the present summary is not limited to a specific number of electrode sites. Each electrode can include its own pulse generator and sensing circuit. However, the present summary is not so limited. The pulse generation and sensing functions can be multiplexed to function with multiple electrodes.

  NS treatment unit 1137 includes components based on management of the controller to stimulate baroreceptors and / or sense ANS parameters related to neural activity or ANS parameters such as blood pressure and respiration. Three interfaces 1142 are shown for use to provide ANS therapy. However, the present subject matter is not limited to a particular number of interfaces or any particular stimulus or sensing function. The pulse generator 1143 is used to supply electrical pulses to the electrodes used to stimulate the baroreceptor site. According to various embodiments, the pulse generator may include a stimulus pulse amplitude, a stimulus pulse, such as a square wave, a triangle wave, a sine wave, a white noise or a wave having a desired harmonic component to mimic other signals. Includes a circuit for setting the frequency, the burst frequency of the pulse, and the pulse form and, in some embodiments, changing. Sensing circuit 1144 is used to detect and process signals from sensors, such as sensors for neural activity, blood pressure, respiration, and the like. A general interface 1142 is shown in which the controller 1123 is used for communication between the pulse generator 1143 and the sensing circuit 1144. Each interface can be used, for example, to control a separate lead. Various embodiments of the NS treatment unit include only a pulse generator for stimulating baroreceptors. For example, the NS treatment unit performs AHT treatment.

  Aspects of this summary designed specifically to treat hypertension by activating the baroreceptor reflex and observing blood pressure and stimulating baroreceptors to suppress sympathetic nerve release from the vasomotor center Related to a long-term implanted stimulation system. Baroreceptors are in various anatomical locations such as the carotid sinus and the aortic arch. Other baroreceptor locations include pulmonary arteries including arterial chords and sites within the atria and ventricular chambers. In various embodiments, the system is integrated into a pacemaker / defibrillator or other electrical stimulation system. The components of the system include a high frequency pulse generator, a sensor that observes blood pressure or other suitable physiological parameters, a lead that applies electrical stimulation to the baroreceptor, and an algorithm that determines the appropriate time to administer the stimulation. Algorithms for manipulating data for display and patient management.

  Various embodiments relate to a system for delivering electrical mediated NS therapy, such as AHT therapy, to a patient. Various embodiments combine a “stand alone” pulse generator with a minimally invasive monopolar lead that directly stimulates baroreceptors near the heart, such as the pulmonary artery. This embodiment can be implanted by a general doctor who lacks expert skills. Various embodiments incorporate a simple implantation system that can sense a parameter indicative of blood pressure. The system can adjust the therapeutic output (waveform amplitude, frequency, etc.) to maintain the desired quality of life. In various embodiments, the implantation system includes a pulse generator and a lead system, and the stimulation electrode is positioned near the endocardial baroreceptor tissue using a transvenous implant technique. Another embodiment includes a system that combines NS treatment with traditional bradyarrhythmia, tachyarrhythmia, and / or congestive heart failure (CHF) treatment. Some embodiments use an additional “baroreceptor lead” that exits the device header and is paced from a modified traditional pulse generation system. In one embodiment, the traditional CRM lead is modified to incorporate a proximal electrode that is naturally positioned near the baroreceptor site. With these leads, the distal electrode provides CRM therapy and the proximal electrode stimulates the baroreceptor.

  The systems according to these embodiments can be used to increase the number of partially successful treatment strategies. As an example, undesirable side effects limit the use of some drugs. Combining the system according to these embodiments with a reduced drug volume is beneficial.

  In various embodiments, the lead and the electrode on the lead are directed against the heart so that the electrode can properly pulse and sense signals from the heart and to the baroreceptor to stimulate the baroreflex. Are physically arranged. Since there are multiple leads and multiple electrodes per lead, the shape is programmed to use one or more special electrodes. According to various embodiments, the baroreflex is stimulated by stimulating the afferent nerve trunk.

  FIG. 12 illustrates a system 1220 that includes a programmer 1222, an implantable neural stimulation (NS) device 1237, and an implantable cardiac rhythm management (CRM) device 1238 according to various embodiments of the present subject matter. Various aspects include a method of communicating between an NS device 1237 such as an AHT device and a CRM device 1238 or between it and other cardiac stimulators. In various embodiments, this communication allows one of the devices 1237 or 1238 to perform a more appropriate treatment (ie, a more appropriate NS treatment or CRM treatment) based on data received from the other device. To do. Some embodiments provide on-demand communication. In various embodiments, this communication enables each of the devices 1237, 1238 to provide a more appropriate treatment (ie, a more appropriate NS treatment or CRM treatment) based on data received from the other device. To do. The illustrated NS device 1237 and CRM device 1238 can wirelessly communicate with each other, and the programmer can wirelessly communicate with the NS device and at least one of the CRM devices 1237, 1238. For example, various embodiments use telemetry coils to wirelessly communicate data and instructions to each other. In other embodiments, data and / or energy communication is by ultrasound means.

  In some embodiments, the NS device 1237 stimulates the baroreflex to perform NS therapy and uses surrogate parameters such as breathing and blood pressure to indicate ANS activity, or directly produces ANS activity. Sense. CRM device 1238 includes cardiac stimulation capabilities such as pacing and defibrillation capabilities. Rather than providing wireless communication between the NS device and the CRM devices 1237, 1238, various embodiments provide a communication cable or an intravenously supplied cable used to communicate between the NS device 1237 and the CRM device 1238, or Provide wire.

  FIG. 13 shows an implantable neural stimulation (NS) device 1337, such as that shown at 1237 in the system of FIG. 12, according to various embodiments of the present subject matter. FIG. 14 shows an implantable cardiac rhythm management (CRM) device 1438, such as that shown at 1238 in the system of FIG. 12, according to various embodiments of the present subject matter. The functions of the NS device 1337 members were previously discussed with respect to FIGS. 9 and 11 (NS portion 1137), and the functions of the CRM device 1238 members were previously discussed with respect to FIG. 11 (CRM portion 1138). For simplicity, these discussions about NS and CRM will not be repeated here. Various embodiments of NS and CRM devices include wireless transceivers 1325 and 1425, respectively, for wireless communication with each other. Various embodiments of NS and CRM devices include telemetry coils or ultrasonic transducers for wireless communication with each other.

  According to various embodiments, for example, the NS device allows data to be exchanged between it and the CRM device, and the NS device is capable of heart rate, minute ventilation, atrial activation, ventricular activation, A telemetry coil is provided that allows the treatment to be modified based on electrophysiological parameters such as cardiac events. In addition, the CRM device modifies therapy based on data received from the NS device such as mean arterial pressure, systolic pressure, diastolic pressure, baroreceptor stimulation rate.

  Some NS device embodiments can be implanted in a patient with an existing CRM so that the functionality of the NS device can be enhanced by receiving physiological data acquired by the existing CRM device. . The functionality of two or more embedded devices is enhanced by providing communication capabilities between or within the embedded devices. In various embodiments, greater functionality can be achieved by designing the devices to communicate wirelessly with each other.

  FIG. 15 illustrates a programmer 1522, such as the programmer 822, 1222 shown in the system of FIGS. 8, 12, or other devices for communicating with the implantable medical device 1237 and / or 1238, according to various embodiments of the present subject matter. Indicates an external device. Another example of an external device includes a personal information terminal (PDA) or a personal laptop or desktop computer in an advanced patient management (APM) system. The illustrated device 1522 includes a control circuit 1545 and a memory 1546. The control circuit 1545 can be implemented using hardware, software, or a combination of hardware and software. For example, according to various embodiments, the control circuit 1545 may execute instructions recorded in the memory 1546 to perform a number of functions, including communication data to the implantable device and / or programming instructions. Including a processor. The illustrated device 1522 further includes a transceiver 1547 and associated circuitry used to communicate with the implantable device. Various embodiments have wireless communication capabilities. For example, various embodiments of circuitry associated with transceiver 1547 include a telemetry coil used to wirelessly communicate with an implantable device. The illustrated device 1522 includes an input / output device 1549 such as a display 1548, keyboard or mouse / pointer, and further includes a communication interface 1550 used for communication with other devices, such as on a communication network.

Application of programmed therapy The NS function and / or CRM function of the system, whether they are implemented as two separate and separate implantable devices, may be integrated as part of a single implantable device. A processor is included to perform the therapy and / or CRM therapy, or a portion of the therapy. In some embodiments, NS treatment provides AHT treatment. These processes can be performed, for example, by a processor executing computer readable instructions recorded in memory. These therapies have a variety of processes and functions and include a number of applications, some of which are identified and discussed below. Since some embodiments of the present subject matter include a combination of two or more of the following processes and functions, these treatment processes and functions are not necessarily mutually exclusive.

Description of Neural Stimulation to Sense Signals Accurately FIGS. 16A-16D are diagrams between electrical stimulation from a neural stimulation (NS) device and sensing by a cardiac rhythm management (CRM) device, according to various embodiments of the present subject matter. 1 illustrates a system and method for avoiding interference. Neural stimulation improves the ability to sense signals and thus reduces or eliminates false positives associated with detection of cardiac events. NS devices include AHT devices in some embodiments. For example, according to some embodiments, the NS device communicates with and avoids or otherwise compensates for baroreflex stimulation so that the CRM device does not unintentionally respond to baroreflex stimulation. Some embodiments automatically synchronize baroreflex stimulation with the appropriate refraction in the heart. For example, some systems automatically synchronize baroreceptor stimulation in or around the pulmonary artery with atrial activation. Thus, the function of the CRM device is adversely affected by detecting far-field noise generated by baroreflex stimulation, even when baroreflex stimulation occurs near a CRM sensor or heart that detects cardiac electrical activity. Not.

  FIG. 16A illustrates an NS function 1651 (as performed by an NS unit or an NS unit in an integrated NS device / CRM device) and an CRM unit (as performed by the CRM device or an integrated NS device / CRM device). 1 illustrates generally a system 1654 including a CRM function 1652 (as done) and an ability 1653 to communicate between the NS function and the CRM function. The illustrated communication is two-way wireless communication. However, this summary considers one-way communication and further considers wired communication. Moreover, the present subject matter integrates NS functions and CRM functions 1651, 1652 into a single implantable device to send and receive communication signals within the device or within a separate implantable device. While baroreflex stimulation as part of neural stimulation has been specifically discussed, this aspect of the present summary avoids or explains unintentional interference that is detectable by the sensor and that arises from other electrical stimulators, Or applicable to compensate in other ways.

  FIG. 16B illustrates a process in which the CRM function does not respond to unintended baroreflex stimulation, according to various embodiments. FIG. 16B shows the process by which the NS device or NS portion 1651 sends a warning or otherwise informs the CRM device or CRM portion when the baroreceptor is electrically stimulated. In the illustrated embodiment, the NS device / NS unit determines at 1655 whether an electrical stimulus, such as a baroreflex stimulus, should be applied. When electrical stimulation is to be applied, the NS device or NS portion 1651 sends a warning 1657 at 1656 or otherwise informs the CRM device or CRM portion 1652 of electrical stimulation. At 1658, electrical stimulation is applied by the NS device / NS unit. At 1659, CRM therapy is performed including sensing. At 1660, the CRM device / CRM unit determines whether a warning 1657 has been received from the NS device / NS unit. If a warning is received, the event detection algorithm will increase the detection threshold and provide a blackout or blanking window, or else an electrical stimulation in the NS device or NS unit will cause an event by the CRM device / CRM unit. To prevent being misunderstood as 1661.

  FIG. 16C includes processes in which the CRM function does not unintentionally react with baroreflex stimulation, according to various embodiments. The CRM device / CRM unit 1652 determines the refractory period of the heart at 1662. At 1663, an enable 1664 corresponding to the refractory period is provided to the NS device / NS unit 1651 if the refractory period is occurring or is expected to occur within a predictable time. The AHT device / AHT unit 1651 determines whether electrical stimulation is desired at 1655. When desired, the AHT device / AHT unit applies electrical stimulation during the refractory period at 1666 as controlled by the enable signal 1664. FIG. 16D shows the refractory period at 1667 in the heart and the baroreflex stimulus 1668 and further shows that the baroreflex stimulus is applied during the refractory period.

  The refractory period includes both an absolute refractory period and a relative refractory period. Heart tissue cannot be stimulated during the absolute refractory period. The required stimulation threshold during the absolute refractory period is essentially infinite. The relative refractory period occurs after the absolute refractory period. If the heart tissue begins to repolarize during the relative refractory period, the stimulation threshold is initially very high and falls to the normal stimulation threshold by the end of the relative refractory period. Thus, according to various embodiments, the neurostimulator is in an absolute refractory period corresponding to a stimulation threshold that is high enough to prevent neural stimulation from capturing heart tissue or part of a relative refractory period. Apply nerve stimulation during.

  Various embodiments of the present subject matter relate to methods for sensing atrial activation and limiting pulmonary artery stimulation to the atrial refractory period to avoid unintentional stimulation of nearby atrial tissue. The implantable baroreceptor stimulator observes atrial activation with an atrial sensing lead. Leads in the pulmonary artery stimulate baroreceptors in the vessel wall. However, instead of continuously stimulating these baroreceptors, stimulation of baroreceptors in the pulmonary artery maintains the intrinsic atrial velocity and activation and avoids capturing the nearby atrial myocardium. Get up during the period. Various embodiments of the present subject matter combine an implantable device that stimulates baroreceptors in the pulmonary artery wall with atrial sensing capabilities. Various embodiments stimulate baroreceptors in the cardiac fat body, heart chamber, and / or afferent nerve.

  FIG. 17 illustrates a system for regulating baroreflex stimulation, according to various embodiments of the present subject matter. The system shown includes a baroreflex stimulator 1751, such as a stimulator that stimulates baroreceptors in and around the pulmonary artery. The baroreflex stimulator is included in a stand-alone NS device or, for example, as an NS unit in an integrated NS device / CRM device. The illustrated stimulator 1751 includes a modulator 1769 that selectively increases or decreases the applied baroreflex stimulation. According to various embodiments, modulator 1769 includes any one of the following modules. Module 1770 for changing the amplitude of the stimulation pulse. A module 1771 for changing the frequency of the stimulation pulse. A module 1772 for changing the burst frequency of the stimulation pulse. The burst frequency is also called the duty cycle. According to various embodiments, the modulator 1769 includes functionality for various combinations of two or more modules 1770, 1771, 1772. Moreover, the stimulator can include a waveform generator capable of providing various waveforms in response to the control signal.

  Various embodiments of the system can control the modulator 1769 of the stimulator 1759 to properly apply a desired level of baroreflex stimulation, a cardiac activity monitor 1773, an adverse event detector 1774, a respiratory monitor 1775. , Any one or any combination of circadian rhythm templates 1776. Each of these 1773, 1774, 1775, 1776 is associated with a method of adjusting the baroreflex signal. According to various embodiments, the system includes means for adjusting the baroreflex signal based on the following parameters or combination of parameters. Cardiac activity (1773). Adverse event (1774). Breathing (1775). Circadian rhythm (1776). Cardiac activity (1773) and adverse events (1774). Cardiac activity (1773) and respiration (1775). Cardiac activity (1773) and circadian rhythm (1776). Adverse events (1774) and breathing (1775). Adverse events (1774) and circadian rhythms (1776). Breathing (1775) and circadian rhythm (1776). Cardiac activity (1773), adverse events (1774), breathing (1775). Cardiac activity (1773), adverse events (1774), circadian rhythm (1776). Cardiac activity (1773), breathing (1775), circadian rhythm (1776). Adverse events (1774), breathing (1775), circadian rhythm (1776). Cardiac activity (1773), adverse events (1774), breathing (1775), circadian rhythm (1776).

  Stimulation is applied to the afferent nerve trunk, such as the vagus nerve, using an intravascularly supplied lead positioned near the cuff electrode or nerve trunk. Stimulation is applied to baroreceptor sites such as those located in the pulmonary artery, aortic arch, and carotid sinus using, for example, an intravascularly supplied lead. Stimulation is applied to a baroreceptor site located within the cardiac fat body by using a lead delivered intravascularly or by fitting an electrode into the fat body. For example, an embodiment of the heart activity detector 1774 includes any one or combination of a heart rate monitor 1777, a minute ventilation monitor 1778, an acceleration monitor 1779. The respiration monitor 1775 functions as a proxy for observing blood pressure. Embodiments of respiratory monitor 1775 include any one or any combination of tidal volume monitor 1780 and minute ventilation module 1781. Embodiments of circadian rhythm template 1776 include any one or any combination of custom generated template 1782 and pre-programmed template 1783. These embodiments are discussed in more detail below with respect to FIGS. 18A-18C, 19A-19B, 20A-20B, 21A-21E, 22, 23A-23C.

  Various embodiments use a circadian rhythm template to provide AHT therapy. Various embodiments use a circadian rhythm template to provide apnea therapy.

Modulation of baroreflex stimulation based on systolic interval The sympathetic or parasympathetic nervous system is a type of systolic interval, primarily the progenitor phase (PEP), sensed electrical activity in the ventricle (eg, sensing “R” waves). It is known to change the time interval between the start of ventricular discharge of blood. The PEP is measured from the sensed electrical event to the onset of pressure increase in the pulmonary artery using a pulmonary artery pressure sensor, or during draining using electrodes located in the right ventricle or extending into the left ventricle Measured at the onset of an increase in intracardiac impedance with a decrease in ventricular volume. At rest, neural stimulation is adjusted to maintain the PEP within a pre-programmed range, as determined by heart rate or physical activity as measured by an accelerometer, for example. A sudden decrease in PEP indicates an increase in sympathetic tone associated with exercise or emotional stress. This condition can be used to reduce neural stimulation that allows for the necessary contractility to meet heart rate increases and metabolic demands. Similarly, dramatically increasing PEP, which follows, represents the end of increased metabolic demand. At this point, blood pressure control by neural stimulation can be resumed.

Modulating baroreflex stimulation based on cardiac activity This summary describes a method for automatically adjusting baroreceptor stimulation based on cardiac activity, as determined by heart rate, ventilation per minute, acceleration, and combinations thereof. . Functionality of the device that electrostimulates baroreceptors is at least relatively high baropacing rates during rest when metabolic demand is relatively low, and progressively lower during physical exercise when metabolic demand increases Increased by applying pressure pacing. The index of cardiac activity is used to automatically regulate baroreceptor electrical stimulation, allowing the implantable antihypertensive device to respond to changes in metabolic demand. According to various embodiments, CRM devices such as pacemakers, AICD devices or CRT devices also have baroreceptor stimulation leads. The device observes cardiac activity via existing methods, for example using mixed sensors. The mixed sensor includes two sensors that measure parameters such as acceleration and ventilation per minute. The output of the mixed sensor becomes a composite parameter. Various NS and AHT therapies use composite parameters derived from two or more sensed parameters as discussed in this disclosure. At rest (low cardiac activity), the device stimulates baroreceptors at a high rate, reduces blood pressure, and controls hypertension. As cardiac activity increases, the device responds by temporarily reducing baroreceptor stimulation. This results in a temporary increase in blood pressure and cardiac output, allowing the body to respond to increased metabolic demands. For example, some embodiments provide baroreflex stimulation during rest and cancel baroreflex stimulation during exercise to match a normal blood pressure response to exercise. A pressure transducer can be used to determine activity. Further, activity can be sensed using a sensor used or used to drive heart rate sensitive pacing. Examples of such sensors include body movement, heart rate, QT sensation, respiratory rate, transthoracic impedance, tidal volume, ventilation per minute, body position, electroencephalogram (EEG), electrocardiogram (ECG), electrooculogram. (EOG), electromyogram (EMG), muscle tone, body temperature, pulse oximeter, time of day, and sensors that detect the progenitor interval from intracardiac impedance.

  Various embodiments of the cardiac activity monitor include mean arterial parameters, pulse pressure determined by the difference between systolic and diastolic pressure, end systolic pressure (pressure at the end of systole), end diastolic pressure (at the end of diastolic phase). A sensor for detecting at least one pressure parameter such as Various embodiments of the cardiac activity monitor include a stroke volume monitor. Heart rate and pressure can be used to guide stroke volume. Various embodiments of the cardiac activity monitor use at least one electrogram measurement to determine cardiac activity. Examples of such electrogram measurements include RR intervals, PR intervals, and QT intervals. Various embodiments of the cardiac activity monitor use at least one electrocardiogram (ECG) measurement to determine cardiac activity.

  18A-18C illustrate a method for adjusting baroreceptor stimulation based on cardiac activity parameters, according to various embodiments of the present subject matter. Cardiac activity can be determined by CRM devices, NS devices, or implantable devices with NS / CRM capabilities. A first process 1884A for adjusting baroreceptor stimulation based on cardiac activity is shown in FIG. 18A. At 1885A, the activity level is determined. According to various embodiments, the determination of the activity level is based on heart rate, minute ventilation, acceleration, or any combination of heart rate, minute ventilation, acceleration. In the process shown, the activity level has two defined binary levels (eg, HI and LO). In some embodiments, the LO level includes no stimulation. It is determined that the activity level is HI or LO. At 1886A, the baroreceptor stimulation level is set based on the determined activity level. The LO stimulation level is set if the activity level is determined to be HI, and the HI stimulation level is set if the activity level is determined to be LO.

  A second process 1884B for adjusting baroreceptor stimulation based on cardiac activity is shown in FIG. 18B. The activity level is determined at 1885B. According to various embodiments, the determination of the activity level is based on heart rate, minute ventilation, acceleration, or any combination of heart rate, minute ventilation, acceleration. In the process shown, the activity level has two or more defined levels or n defined levels. It is determined that the activity level is level 1, level 2... Or level n. Activity level labels correspond to increasing activity. At 1886B, a baroreceptor stimulation level is set based on the determined activity level. Available stimulation levels include level n... Level 2 and level 1, where the stimulation level indicator corresponds to increasing stimulation. According to various embodiments, the selected baroreceptor stimulation level is inversely proportional to the determined activity level. For example, if it is determined that the cardiac activity level is at the highest level n, then the stimulation level is set to the lowest level n. If it is determined that the stimulation level is first or second from the lowest level, respectively, level 1 or level 2, respectively, the stimulation level is set to the first or second from the highest level, level 1 or level 2, respectively. The

  Another process 1884C for modulating baroreceptor stimulation based on cardiac activity is shown in FIG. 18C. At 1887, the acquired cardiac activity parameter is compared to the target activity parameter. If the acquired cardiac activity is lower than the target activity parameter, baroreceptor stimulation increases at 1888. If the acquired cardiac activity is higher than the target activity parameter, baroreceptor stimulation decreases at 1889.

  An aspect of the present subject matter relates to a method for automatically adjusting the intensity of baroreceptor stimulation based on respiration as determined by tidal volume or minute ventilation. Instead of applying continuous baroreceptor stimulation, the NS device uses respiration as a surrogate for blood pressure to observe the hypertension level and deliver the appropriate treatment level so that the device can adjust the treatment level. To. This summary uses a respiratory index, such as impedance, to automatically adjust baroreceptor stimulation to the determined tidal volume or minute ventilation. Thus, the implantable NS device can determine the level of hypertension in the patient and responds by applying an appropriate level of therapy. In various embodiments, the implantable NS device includes a sensor that measures tidal volume or minute ventilation. For example, various embodiments measure transthoracic impedance to obtain respiratory rate. The device receives this data from the CRM device in some embodiments. NS devices regularly observe these respiratory parameters. When breathing decreases or stays below the programmed target, the device stimulates the baroreceptor at a high rate, reduces blood pressure, and controls hypertension. As the mean arterial pressure increases toward the target, the device responds by decreasing baroreceptor stimulation. In this way, the AHT device continuously provides an appropriate level of treatment.

  19A-19B illustrate a method according to various embodiments of the present subject matter, ie, a method for adjusting baroreceptor stimulation based on respiratory parameters. The respiratory parameter can be determined by a CRM device, NS device, or an implantable device having NS / CRM capabilities. One embodiment for adjusting baroreceptor stimulation based on respiratory parameters is shown at 1910A in FIG. 19A. The respiratory level is determined at 1911 and the baroreceptor stimulation level is set at 1912 based on the determined respiratory level. According to various embodiments, the desired pressure pacing level is adjusted at 1913. For example, one embodiment compares the parameter obtained at 1914 with the target parameter. Pressure pacing can be increased at 1915 or decreased at 1916 based on the comparison of the acquired parameter to the target parameter.

  One embodiment of a method for adjusting baroreceptor stimulation based on respiratory parameters is shown at 1910B in FIG. 19B. At 1916, a baroreflex event trigger occurs, which results in an algorithm for the baroreflex stimulation process. At 1917, respiration is compared to the target parameter. Baroreflex stimulation increases at 1918 if respiration is below the target and decreases at 1919 if respiration exceeds the target. According to various embodiments, if the breath falls within the blanking window, the stimulus does not change. Various embodiments use memory to provide a hysteresis effect to stabilize the applied stimulus and baroreflex response. Moreover, in various embodiments, the respiratory target is modified during treatment based on various factors such as time of day or activity level. At 1920, it is determined whether to continue the baroreflex treatment algorithm based on, for example, receiving a sensed parameter or event interruption. If the baroreflex algorithm is to be continued, the process returns to 1917 where respiration is again compared to the target parameter, otherwise the baroreflex algorithm is stopped at 1921.

Modulation of baroreflex stimulation based on adverse events Aspects of this summary are to detect adverse cardiac events and automate baroreceptor stimulation to increase vasodilator response and potentially prevent or reduce myocardial ischemic damage. Including a method of increasing automatically. Various embodiments include a feedback mechanism in a cardiac rhythm management device (such as a pacemaker, AICD or CRT device) that also has a stimulation lead to electrically stimulate baroreceptors. The device observes cardiac electrical activity by existing methods. Ventricular fibrillation (VF) and atrial fibrillation (AF), ventricular tachycardia (VT) and atrial tachycardia (AT) exceeding a predetermined rate, dyspnea detected by minute ventilation sensor, angina In the case of adverse cardiac events such as decompensation, ischemia, the device responds by increasing baroreceptor stimulation to the maximum acceptable level. As a result, blood pressure is temporarily reduced, potentially preventing or avoiding myocardial damage due to ischemia. The functionality of a device for treating hypertension can be expanded if it can respond to adverse cardiac events by temporarily adjusting the extent of baroreceptor stimulation. Event detection algorithms automatically adjust baroreceptor stimulation, allowing implantable AHT devices to respond to adverse events by increasing baroreceptor stimulation, potentially preventing or reducing myocardial ischemic damage Let

  FIGS. 20A-20B illustrate a method of modulating baroreceptor stimulation based on the detection of adverse events, according to various embodiments of the present subject matter. Adverse events can be determined by CRM devices, NS devices, or implantable devices with NS / CRM capabilities. FIG. 20A illustrates one embodiment of adjusting baroreceptor stimulation based on detection of adverse events. At 2090A, it is determined whether an adverse event has been detected. If no adverse event is detected, normal pressure pacing (pressure pacing with normal procedure) is performed at 2091A. If an adverse event is detected, enhanced pressure pacing is performed at 2092. In various embodiments, maximum allowable pressure pacing is performed when an adverse event is detected. Other pressure pacing procedures can be performed. For example, various embodiments apply pressure pacing stimulation to refrain from pressure pacing therapy when an adverse event is detected, and various embodiments refrain from pressure pacing therapy when an adverse event is detected. Apply pacing stimulus. FIG. 20B illustrates one embodiment of adjusting baroreceptor stimulation based on detection of adverse events. At 2090B, it is determined whether an adverse event has been detected. If no adverse event is detected, normal pressure pacing (pressure pacing with normal procedure) is performed at 2091B. If an adverse event is detected, the event is identified at 2093 and appropriate pressure pacing is applied at 2094 to the identified adverse event. For example, appropriate blood pressure treatment differs from ischemia with respect to ventricular fibrillation. According to various embodiments, the desired pressure pacing is adjusted for events identified at 2095. For example, one embodiment compares 2096 the acquired parameter with the target parameter. Pressure pacing can be increased at 2097 or decreased at 2098 based on the comparison of the acquired parameter to the target parameter.

  According to various embodiments, adverse events include detectable precursors so that treatment can be applied to prevent cardiac arrhythmias. In some embodiments, adverse events include both cardiac events and non-cardiac events such as stroke. Furthermore, some embodiments detect both arrhythmia and nonarrhythmic events as adverse events.

Modulation of baroreflex stimulation based on circadian rhythm Certain aspects of the present subject matter relate to methods of stimulating baroreflex in hypertensive patients so as to mimic the natural variations in blood pressure that occur over a 24-hour period. Reduction in hypertension reflexes occurs during prolonged baroreceptor stimulation without changing the inherent arterial pressure fluctuations. According to various embodiments, the implantable device stimulates baroreceptors in the carotid sinus, pulmonary artery or aortic arch using, for example, short high frequency bursts (square waves having a frequency in the range of about 20-150 Hz). Designed to do. Some various embodiments directly stimulate the carotid sinus branch, aortic nerve or vagus nerve with a cuff electrode. However, bursts do not occur at a constant rate. Rather, the stimulation frequency, amplitude, and / or burst frequency goes up and down during the day, mimicking the natural circadian rhythm.

  Thus, various embodiments of NS devices account for natural arterial pressure fluctuations that occur in both normal and hypertensive individuals. In addition to activity related changes in mean arterial pressure, subjects also show consistent pressure fluctuations over a 24 hour cycle. A device that provides periodic baroreceptor stimulation mimics the inherent circadian rhythm and allows reflex inhibition and systemic blood pressure reduction without disturbing this rhythm. This summary provides a pacing procedure that changes baroreceptor stimulation frequency / amplitude to reduce mean arterial pressure without disturbing the inherent circadian rhythm.

  21A-21E show the circadian rhythm. FIG. 21A shows the circadian rhythm associated with the mean arterial pressure for 24 hours from noon to noon. FIG. 21B shows a circadian rhythm associated with a 24-hour heart rate from noon to noon. FIG. 21C shows the circadian rhythm associated with the rate of change of cardiac output (SV%) from noon to noon for 24 hours. FIG. 21D shows the circadian rhythm associated with the rate of change in cardiac output (CO) from noon to noon for 24 hours. FIG. 21E shows the circadian rhythm associated with the rate of change in total peripheral vascular resistance (% TPR), an index of vasodilation, from noon to noon for 24 hours. Various embodiments graph absolute values, and various embodiments graph percent values. In these figures, the shaded portion corresponds to the night time from approximately 10 pm to 7 am and therefore corresponds to rest or sleep time. For example, referring to FIGS. 21A and 21B, it is clear that both mean arterial pressure and heart rate decrease during the rest period. High blood pressure and heart rate can adversely affect rest. Moreover, low blood pressure and heart rate during the day adversely affect an individual's energy level.

  Various embodiments of the present subject matter regulate baroreflex stimulation using pre-programmed templates that are intended to adapt circadian rhythm to multiple subjects. Various embodiments of the present subject matter generate customized templates to suit a subject.

  FIG. 22 illustrates a method for adjusting baroreceptor stimulation based on circadian rhythm according to various embodiments of the present subject matter using a customized circadian rhythm template. The illustrated method 2222 senses and records parameters associated with hypertension at 2223. Examples of such parameters include heart rate and mean arterial pressure. At 2224, a circadian rhythm template is generated based on these recorded parameters. At 2225, baroreflex stimulation is adjusted using the circadian rhythm template generated at 2224.

Modulation of baroreflex stimulation to provide desired cardiac output Certain aspects of the present disclosure provide NS therapy to reduce systemic blood pressure by stimulating baroreflex and cardiac pacing for rate control The present invention relates to an implantable medical device that further provides cardiac pacing therapy using a lead. Baroreflex stimulation and cardiac pacing occur in series, allowing blood pressure to drop without sacrificing cardiac output.

  According to various embodiments, the baroreflex stimulator communicates with a separate implantable CRM device and uses existing pacing leads. In various embodiments, baroreflex stimulation occurs via baroreceptors in the pulmonary artery, carotid sinus, or aortic arch with electrodes placed in or around the vessel wall. In various embodiments, afferent nerves such as the aortic nerve, carotid sinus branch, or vagus nerve are stimulated directly by the cuff electrode.

  Baroreflex stimulation rapidly causes vasodilation and reduces systemic blood pressure. To compensate for the simultaneous decrease in cardiac output, the pacing rate is increased during baroreflex stimulation. The present summary allows blood pressure to be gradually reduced via baroreflex stimulation, while avoiding a decrease in cardiac output associated with such stimulation by combining baroreflex stimulation with cardiac pacing, Allows the implantable device to maintain cardiac output during blood pressure control.

  23A-B illustrate a method for adjusting baroreceptor stimulation based on cardiac output parameters, according to various embodiments of the present subject matter. FIG. 23A illustrates one embodiment of adjusting baroreceptor stimulation based on cardiac output parameters. In the process 2326A shown, it is determined whether a baroreflex stimulus is applied at 2327. If baroreflex stimulation is not applied, the subject matter at 2328 performs appropriate pacing therapy, if any, with an appropriate pacing rate. If baroreflex stimulation is not applied, this summary improves pacing therapy at 2329 at a high pacing rate to maintain cardiac output.

  FIG. 23B illustrates one embodiment of adjusting baroreceptor stimulation based on cardiac output parameters. In the process 2326B shown, baroreflex stimulation is applied at 2330 and it is determined at 2331 whether the cardiac output is appropriate. If it is determined that the cardiac output is not appropriate, the pacing rate is increased at 2332 in order to maintain proper cardiac output.

  According to various embodiments, the existing pacing rate is increased by a predetermined factor during baroreflex stimulation to maintain cardiac output. In various embodiments, the pacing rate is initiated during baroreflex stimulation to maintain cardiac output. Adjusting baroreflex stimulation to provide the desired cardiac output can be performed by atrial rate control and ventricular rate control, AV delay control, resynchronization, multi-site stimulation. Alternatively, cardiac output can be observed by right ventricular impedance using an electrode in the right ventricular cavity, or by left ventricular impedance using an electrode in or spanning the left ventricular cavity, and the pacing rate can be In order to maintain the output, it can be increased using the application of neural stimulation.

Modulating Baroreflex Stimulation to Reconstruct the Curing Process Aspects of this summary involve baroreflex stimulation methods used by implantable NS devices to lower systemic blood pressure in patients with refractory hypertension. The baroreflex stimulation algorithm gradually increases the baroreflex stimulation to slowly adjust the blood pressure toward the programmable target. This algorithm prevents the central nervous system from adapting to an increased level of baroreflex stimulation that normally mitigates the pressure-lowering effect. Moreover, the gradual nature of blood pressure changes allows patients to better tolerate treatment without sudden changes in systemic blood pressure and cardiac output.

  This summary avoids the central nervous system from adapting to increased baroreflex stimulation and allows blood pressure levels over time to allow reversal of the arteriosclerosis process caused by previous hypertensive conditions present in the patient. A specific algorithm or process is provided that is designed to slowly reduce the aging and avoid a decrease in cardiac output during baroreceptor stimulation. Inversion of the arterial system is expected over time to reconstruct the sclerosis process initiated by previously existing hypertension. The slow and gradual decline in mean / median blood pressure allows a slow reversal of this curing process via reverse reconstruction. Blood pressure is reduced without compromising cardiac output in the process, thus avoiding undesirable patient symptoms.

  In various embodiments, the device stimulates baroreceptors in the pulmonary artery, carotid sinus, or aortic arch by electrodes placed in or adjacent to the vessel wall. In various embodiments, afferent nerves such as the aortic nerve, carotid sinus branch, or vagus nerve are stimulated directly by the cuff electrode. Stimulated baroreflex rapidly dilates blood vessels and reduces systemic blood pressure. However, rather than stimulating the baroreflex at a constant high level, the device of the present subjecting first stimulates at a slightly increased level and then gradually increases the stimulus over a period of, for example, weeks or months . The rate of change is determined by the device based on the current and target arterial pressure. In various embodiments, the system determines the rate of change based on direct or indirect measurements of cardiac output to ensure that no pressure reduction occurs at the expense of reduced cardiac output. In various embodiments, the baroreflex stimulation rate is not constant, but has a white noise type distribution to more closely mimic the neural communication distribution. By mimicking the neural communication distribution, the baroreflex is expected to be more responsive to the stimulus, thus reducing the threshold for stimulating the baroreflex.

  FIG. 24 illustrates a method of adjusting baroreceptor stimulation to reverse reconstitution hardening according to various embodiments of the present subject matter. A baroreflex event trigger occurs at 2433. This trigger includes any event that initiates baroreflex stimulation, including activation of the AHT device. At 2434, the algorithm is implemented to increase baroreflex stimulation with a predetermined rate of change to gradually lower blood pressure to the target pressure to reverse reconstruct the curing process. At 2435, it is determined whether to continue the baroreflex stimulation algorithm. The algorithm is stopped at 2436 based on, for example, event interruption, sensed parameters, and / or reaching target blood pressure. At 2437, it is determined whether the cardiac output is acceptable. If the cardiac output is not acceptable, at 2438, the rate of change of the baroreflex stimulation is modified based on the cardiac output.

Baroreflex stimulation to treat myocardial infarction Following myocardial infarction, myocytes in the infarcted area die and are replaced by scar tissue that has mechanical and elastic properties that differ from functional myocardium. Over time, this infarcted area may become thin and dilate, causing redistribution of myocardial stress throughout the heart. Ultimately, this process leads to mechanical stress impairment and heart failure in high stress areas. High stress regions are referred to as severely “loaded” and stress reduction is referred to as “unlaoding”. An apparatus for treating acute myocardial infarction is desirable so as to prevent or reduce myocardial damage.

  One aspect of this summary relates to an implantable device for observing cardiac electrical activity. After detection of myocardial infarction, the device electrically stimulates the baroreflex by stimulating baroreceptors in or adjacent to the vessel wall and / or directly stimulating pressure sensitive nerves. Increased baroreflex stimulation compensates for decreased baroreflex sensitivity and improves clinical outcome in patients following myocardial infarction. Implantable devices (eg CRM devices) observe cardiac electrical activity. After detecting myocardial infarction, the device stimulates the baroreflex. Some embodiments of the device stimulate baroreceptors in the pulmonary artery, carotid sinus, or aortic arch with electrodes placed in or adjacent to the vessel wall. In various embodiments, afferent nerves, such as the aortic nerve, are stimulated directly by a lead or cuff electrode placed in a vein near the afferent nerve. A afferent nerve, such as the carotid sinus branch or vagus nerve, is directly stimulated by a lead or cuff electrode placed in a vein near the afferent nerve. In various embodiments, the cardiac fat pad is stimulated using an electrode fixed to the fat pad or a lead delivered intravenously into a cavity or blood vessel adjacent to the fat pad.

  Baroreflex stimulation rapidly dilates blood vessels and reduces systemic blood pressure. This compensates for reduced baroreflex sensitivity and reduces myocardial infarction. According to various embodiments, systemic blood pressure or surrogate parameters are observed during baroreflex stimulation to ensure that an appropriate level of stimulation is delivered. Some aspects and embodiments of the present subject matter provide baroreflex stimulation to prevent ischemic damage following myocardial infarction.

  FIGS. 25A-25B illustrate systems and methods for detecting myocardial infarction and performing pressure pacing in response to the detected myocardial infarction, according to various embodiments of the present subject matter. FIG. 25A shows a system that includes a myocardial infarction detector 2539 and a baroreflex or baroreceptor stimulator 2540. Myocardial infarction can be detected using, for example, an electrocardiogram. For example, a template is compared with an electrocardiogram to determine myocardial infarction. Another example is detecting a change in the elevation of the ST portion to detect myocardial infarction. In various embodiments, detector 2539 and stimulator 2540 are integrated into a single implantable device, such as in an AHT device or CRM device. In various embodiments, detector 2539 and stimulator 2540 are implemented as separate implantable devices suitable for communicating with each other.

  FIG. 25B illustrates a method for detecting myocardial infarction and performing pressure pacing in response to the detected myocardial infarction, according to various embodiments of the present subject matter. At 2541, it is determined whether a myocardial infarction has occurred. After determining that a myocardial infarction has occurred, the baroreflex is stimulated at 2542. For example, in various embodiments, baroreceptors in and around the pulmonary artery are stimulated using a lead delivered to the pulmonary artery via the right atrium and pulmonary valve. Other embodiments stimulate other baroreceptor sites and pressure sensitive nerves. Some embodiments observe systemic blood pressure or surrogate parameters at 2543 and determine whether stimulation should be adjusted based on this observation at 2544. If the stimulus is to be adjusted, it is adjusted with baroreflex stimulation, 2545. Examples of adjustments include changing the amplitude, frequency, burst frequency and / or waveform of the stimulus.

  Neural stimulation such as baroreflex stimulation can be used to unload after myocardial infarction. Various embodiments use an acute myocardial infarction detection sensor, such as an ischemia sensor, in the feedback control system of the NS device. However, a myocardial infarction detection sensor is not necessary. For example, a stimulation lead can be implanted after myocardial infarction. In various embodiments, a stimulation lead is implanted into the pulmonary artery via the right atrium to stimulate baroreceptors in and around the pulmonary artery. Various embodiments include stimulation cuffs or leads to stimulate afferents, electrode fixators or leads to stimulate cardiac fat pads, and other baroreceptors provided elsewhere in this disclosure. Embed the lead to stimulate.

  Electrical pre-excitation of a heavily loaded area reduces the loading of this area. This pre-excitation activates the sympathetic nerves, increases the overall stress, and significantly reduces the cardiac output that ultimately leads to harmful remodeling of the heart. This process can be avoided by increasing neural stimulation to reduce the impact of this reflex. Thus, activation of the parasympathetic nervous system during pre-excitation prevents undesired side effects of unloading due to electrical pre-excitation.

  Those skilled in the art will appreciate that the modules and other circuits shown and described herein can be implemented using software, hardware, or a combination of software and hardware. As such, the term module is intended to encompass software implementations, hardware implementations, and software and hardware implementations.

  The methods presented in this disclosure are not intended to exclude other methods within the scope of the present subject matter. Those of skill in the art upon reading and understanding the present disclosure will understand other methods within the scope of the present subject matter. The above embodiments and the portions of the illustrated embodiments are not necessarily mutually exclusive. These embodiments and their parts can be combined. For example, various embodiments combine two or more illustrated processes. Two or more sensed parameters are combined into a composite parameter that is used to deliver the desired neural stimulation (NS) or anti-term blood pressure (AHT) therapy. In various embodiments, the methods provided above are implemented as computer data signals embodied in a carrier wave or propagation signal that indicates a sequence of instructions that, when performed by a processor, cause the processor to perform the respective method. In various embodiments, the methods provided above are implemented as a set of instructions included in a computer-accessible medium that can instruct a processor to perform each method. In various embodiments, the medium is a magnetic medium, an electronic medium, or an optical medium.

  While various different embodiments have been shown and described herein, it should be understood that any arrangement calculated to accomplish the same purpose may be used in place of the particular embodiment shown. Will be recognized by the vendor. This application is intended to cover adaptations and variations of the present subject matter. It should be understood that the above description is illustrative and not restrictive. Combinations of the above embodiments and some combinations of the above embodiments in other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the present subject matter should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

The neural mechanism of peripheral vascular control is shown. Showing the heart. Showing the heart. Showing the heart. Fig. 6 shows baroreceptors and afferents in the area of the carotid sinus and aortic arch. The baroreceptors in and around the pulmonary artery are shown. The baroreceptor field within the aortic arch, arterial duct and pulmonary trunk is shown. 2 shows a known relationship between respiration and blood pressure when a baroreflex is stimulated. FIG. 6 shows blood pressure in response to carotid nerve stimulation in hypertensive dogs during 6 months of intermittent carotid nerve stimulation. 1 illustrates a system including an implantable medical device (IMD) and a programmer, according to various embodiments of the present subject matter. 9 illustrates an implantable medical device (IMD), such as that shown in the system of FIG. 8, according to various embodiments of the present subject matter. Fig. 6 illustrates a baroreceptor stimulation lead having an integrated pressure sensor (IPS), according to various embodiments of the present subject matter. FIG. 9 illustrates an implantable medical device (IMD) as shown in FIG. 8 having a neural stimulation (NS) unit and a cardiac rhythm management (CRM) unit according to various embodiments of the present subject matter. 1 illustrates a system including a programmer, an implantable neural stimulation (NS) device, and an implantable cardiac rhythm management (CRM) device, according to various embodiments of the present subject matter. 13 illustrates an implantable neural stimulation (NS) device, such as that shown in the system of FIG. 12, according to various embodiments of the present subject matter. 13 illustrates an implantable cardiac rhythm management (CRM) device, such as that shown in the system of FIG. 12, according to various embodiments of the present subject matter. 13 illustrates a programmer, or other external device in communication with an implantable medical device, as shown in the systems of FIGS. 8 and 12, according to various embodiments of the present subject matter. 2 illustrates a system and method for avoiding interference between electrical stimulation from a neural stimulation (NS) device and sensing by a cardiac rhythm management (CRM) device, according to various embodiments of the present subject matter. 2 illustrates a system and method for avoiding interference between electrical stimulation from a neural stimulation (NS) device and sensing by a cardiac rhythm management (CRM) device, according to various embodiments of the present subject matter. 2 illustrates a system and method for avoiding interference between electrical stimulation from a neural stimulation (NS) device and sensing by a cardiac rhythm management (CRM) device, according to various embodiments of the present subject matter. 2 illustrates a system and method for avoiding interference between electrical stimulation from a neural stimulation (NS) device and sensing by a cardiac rhythm management (CRM) device, according to various embodiments of the present subject matter. 1 illustrates a system for regulating baroreflex stimulation, according to various embodiments of the present subject matter. 6 illustrates a method of modulating baroreceptor stimulation based on cardiac activity parameters, according to various embodiments of the present subject matter. 6 illustrates a method of modulating baroreceptor stimulation based on cardiac activity parameters, according to various embodiments of the present subject matter. 6 illustrates a method of modulating baroreceptor stimulation based on cardiac activity parameters, according to various embodiments of the present subject matter. 6 illustrates a method of adjusting baroreceptor stimulation based on respiratory parameters according to various embodiments of the present subject matter. 6 illustrates a method of adjusting baroreceptor stimulation based on respiratory parameters according to various embodiments of the present subject matter. 6 illustrates a method of modulating baroreceptor stimulation based on detection of an adverse event, according to various embodiments of the present subject matter. Indicates circadian rhythm. Indicates circadian rhythm. Indicates circadian rhythm. Indicates circadian rhythm. Indicates circadian rhythm. 6 illustrates a method for modulating baroreceptor stimulation based on circadian rhythm according to various embodiments of the present subject matter. 6 illustrates a method of adjusting baroreceptor stimulation based on cardiac output parameters, according to various embodiments of the present subject matter. 6 illustrates a method of modulating baroreceptor stimulation to reverse reconstitution hardening, according to various embodiments of the present subject matter. 2 illustrates systems and methods for detecting myocardial infarction and performing pressure pacing in response to the detected myocardial infarction, according to various embodiments of the present subject matter.

Claims (39)

A pulse generator that generates a baroreflex stimulation signal as part of baroreflex treatment;
A lead electrically connected to the pulse generator and supplied intravascularly to the heart, wherein the lead is in or near the heart to send the baroreflex stimulation signal to a baroreceptor region in or near the heart A lead, wherein the lead is adapted to be fed to the pulmonary artery via a right ventricle and a pulmonary valve to position the electrode in the pulmonary artery;
A pressure sensor that senses blood pressure and provides a signal indicating the effectiveness of the baroreflex treatment;
A control device connected to the pulse generator for controlling the baroreflex stimulation signal and connected to the sensor for adjusting the baroreflex stimulation signal based on the blood pressure, the control device comprising: By controlling the pulse generator, the baroreflex stimulation signal is configured to provide a target pressure, and the controller compensates for a delayed physiological response to changes in the baroreflex stimulation and continuously applies the target pressure. And a controller that is further configured to adjust the baroreflex stimulation signal using the sensed blood pressure to avoid disconnection.   The controller generates the baroreflex stimulation signal to reduce the sensed blood pressure from hypertension, determines that the sensed blood pressure is decreasing from the hypertension to the target pressure, and The apparatus of claim 1, wherein the apparatus is configured to respond by reducing stimulation before the reducing blood pressure reaches the target pressure.   The controller controls the pulse generator to reduce the sensed blood pressure from hypertension and determines that the sensed blood pressure is maintained or increased above the target pressure. The device of claim 1, wherein the device is configured to respond by increasing stimulation. The controller is further adapted to determine the current cardiac demand and to consider the current cardiac demand when adjusting the baroreflex stimulation signal to compensate for a delayed physiological response to changes in baroreflex stimulation. The apparatus of claim 1.   The apparatus of claim 1, wherein the electrode is positioned proximate to an arterial chord.   6. The device according to claim 1, further comprising a sensing circuit for sensing a signal indicative of a cardiac refractory period, wherein the sensing circuit is connected to the control device.   The pulse generator is further adapted to generate a cardiac pacing signal, and the lead further includes a second electrode positioned to send the cardiac pacing signal to capture the heart. 6. The apparatus according to any one of 6. A second pulse generator for generating a cardiac pacing signal, wherein the second pulse generator is connected to the controller;
A second lead connected to the second pulse generator, the second lead including at least one electrode positioned to send the cardiac pacing signal to capture the heart The apparatus according to claim 1, further comprising: Sensing means for sensing an electrical signal indicative of a cardiac event;
6. The means for detecting an electrical signal indicative of the cardiac event, the means for detecting the electrical signal further comprising: means configured to compensate the baroreflex stimulation signal. The apparatus according to any one of 7 to 8. The sensing means includes an event detection routine for identifying the occurrence of a cardiac event based on the sensed electrical signal;
The means for detecting an electrical signal indicative of the cardiac event includes means for identifying when the baroreflex stimulation signal is applied, and means for adjusting an event detection routine to consider the baroreflex stimulation signal. The apparatus according to claim 9.   11. The apparatus of claim 10, wherein means for adjusting an event detection routine to take into account the baroreflex stimulation signal includes means for increasing a threshold of the event detection routine.   11. The means for adjusting an event detection routine to take into account the baroreflex stimulation signal includes means for providing a blanking window that prevents identification of event occurrence while the baroreflex stimulation signal is being applied. The device described in 1. The sensing means includes means for identifying a refractory period;
The apparatus of claim 9, wherein the means for detecting an electrical signal indicative of the cardiac event includes means for instructing the controller to apply the baroreflex stimulation signal during the refractory period.   The controller is adapted to communicate with a cardiac event detector to consider an applied baroreflex stimulation therapy, wherein the cardiac event detector transmits an electrical signal indicative of an event to the applied baroreflex stimulation. The device of claim 9, wherein the device is distinguishable from treatment.   The controller is adapted to provide a signal indicative of the occurrence of a baroreflex stimulus to the cardiac event detector, the cardiac event detector modifying an event detection routine to account for the occurrence of the baroreflex stimulus 15. The device according to claim 14, which makes it possible to do so.   The controller is adapted to receive a signal from the cardiac event detector corresponding to a refractory period, and the controller is further adapted to apply baroreflex stimulation therapy during the refractory period; The apparatus according to claim 14.   The apparatus of claim 9, wherein the means for detecting an electrical signal indicative of the cardiac event is incorporated into the implantable medical device.   The apparatus of claim 9, wherein means for detecting an electrical signal indicative of the cardiac event is not incorporated into the implantable medical device.   The apparatus according to claim 1, wherein the lead includes the pressure sensor.   The controller provides the baroreflex stimulation during application of a post-myocardial infarct region unload treatment to moderate an increase in sympathetic nervous system tension and is desired during application of an unload treatment for reconstruction control 20. The apparatus of claim 19, wherein the apparatus is adapted to adjust the baroreflex stimulation pulse to maintain the parameters of the desired range.   21. The apparatus of claim 20, wherein the desired parameter comprises a cardiac output parameter.   21. The apparatus of claim 20, wherein the desired parameter comprises a sympathetic tone parameter. A cardiac activity monitor that senses cardiac activity and provides a signal indicative of said cardiac activity;
A modulator that receives the signal indicative of cardiac activity and adjusts the baroreflex stimulation signal based on the signal indicative of cardiac activity to change the baroreflex treatment from a first baroreflex treatment to a second baroreflex treatment; The apparatus according to claim 1, further comprising:   24. The apparatus of claim 23, wherein the heart activity monitor includes a heart rate sensor and the signal indicative of heart activity includes a heart rate signal.   25. A device according to claim 23 or 24, wherein the cardiac activity monitor comprises a respiratory monitor and the signal indicative of cardiac activity comprises a respiratory signal.   26. The apparatus according to any of claims 23 to 25, wherein the cardiac activity monitor includes an acceleration sensor and the signal indicative of cardiac activity includes an acceleration signal.   27. The apparatus according to any of claims 23 to 26, wherein the cardiac activity monitor includes a sensor that senses at least one pressure parameter, and the signal indicative of cardiac activity includes a signal indicative of the at least one pressure parameter.   28. Apparatus according to any of claims 23 to 27, wherein the cardiac activity monitor comprises a stroke volume monitor and the signal indicative of cardiac activity comprises a signal indicative of stroke volume.   The heart activity monitor includes a monitor that measures at least one electrogram measurement, and the signal indicative of cardiac activity includes a signal indicative of the at least one electrogram measurement. Equipment.   30. The cardiac activity monitor according to any of claims 23 to 29, wherein the cardiac activity monitor includes a monitor that measures at least one electrocardiogram (ECG) measurement, and the signal indicative of cardiac activity includes a signal indicative of the at least one ECG measurement. apparatus. An adverse event detector that senses an adverse event and provides a signal indicative of the adverse event;
A modulator that receives the signal indicative of the adverse event and adjusts the baroreflex stimulation signal based on the signal indicative of the adverse event to change the baroreflex treatment from a first baroreflex treatment to a second baroreflex treatment. The apparatus according to claim 1, further comprising:   32. The apparatus of claim 31, wherein the adverse event comprises an adverse cardiac event.   35. The device of claim 32, wherein the adverse cardiac event comprises an arrhythmia.   35. The device of claim 32, wherein the adverse cardiac event comprises a stroke.   32. A device according to any of claims 1, 19, 23, 31 wherein the controller is adapted to adjust the amplitude of the baroreflex stimulation signal based on the blood pressure.   36. Apparatus according to any of claims 1, 19, 23, 31, 35, wherein the frequency of the baroreflex stimulation signal is adjusted.   36. Apparatus according to any of claims 1, 19, 23, 31, 35, wherein the pulse frequency of the baroreflex stimulation signal is adjusted.   36. Apparatus according to any of claims 1, 19, 23, 31, 35 wherein the form of the baroreflex stimulation signal is adjusted.   36. The device according to any of claims 1, 19, 23, 31, 35, wherein two or more properties selected from the group of properties consisting of amplitude, frequency and pulse frequency of the baroreflex stimulation signal are adjusted.

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