Patent Publication Number: US-8126560-B2

Title: Stimulation lead for stimulating the baroreceptors in the pulmonary artery

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The following commonly assigned U.S. patent applications are related, are all filed on the same date as the present application and are all herein incorporated by reference in their entirety: “Baroreflex Stimulation System to Reduce Hypertension,” Ser. No. 10/746,134; and “Lead for Stimulating the Baroreceptors in the Pulmonary Artery,” Ser. No. 10/746,861. 
     FIELD 
     This application relates generally to implantable medical devices and, more particularly, to systems, devices and methods for reducing hypertension using baroreceptor stimulation. 
     BACKGROUND 
     Medical leads have a distal end having one or more electrodes and a proximal end having a terminal that is coupled to a pulse generator. Electrical therapy is delivered from the pulse generator to the body via the electrode. 
     Hypertension is a cause of heart disease and other related cardiac co-morbidities. Hypertension occurs when blood vessels constrict. As a result, the heart works harder to maintain flow at a higher blood pressure, which can contribute to heart failure. Many patients who suffer from hypertension do not respond to treatment, such as treatments related to lifestyle changes and hypertension drugs. 
     A pressoreceptive region is capable of sensing changes in pressure, such as changes in blood pressure. Pressoreceptor regions are referred to herein as baroreceptors, which generally include any sensors of pressure changes. For example, baroreceptors include afferent nerves and further include sensory nerve endings that are sensitive to the stretching of the wall that results from increased blood pressure from within, and function as the receptor of a central reflex mechanism that tends to reduce the pressure. Baroreflex functions as a negative feedback system, and relates to a reflex mechanism triggered by stimulation of a baroreceptor. Increased pressure stretches blood vessels, which in turn activate baroreceptors in the vessel walls. Activation of baroreceptors naturally occurs through internal pressure and stretching of the arterial wall, causing baroreflex inhibition of sympathetic nerve activity (SNA) and a reduction in systemic arterial pressure. An increase in baroreceptor activity induces a reduction of SNA, which reduces blood pressure by decreasing peripheral vascular resistance. 
     The general concept of stimulating afferent nerve trunks leading from baroreceptors is known. For example, direct electrical stimulation has been applied to the vagal nerve and carotid sinus using nerve cuffs. Research has indicated that electrical stimulation of the carotid sinus nerve can result in reduction of experimental hypertension, and that direct electrical stimulation to the pressoreceptive regions of the carotid sinus itself brings about reflex reduction in experimental hypertension. 
     What is needed is a less invasive technique for providing long-term electrical stimulation of the baroreflex. 
     SUMMARY 
     One aspect provides a lead for placement in the pulmonary artery. The lead includes a flexible lead body extending from a proximal end to a distal end, the distal end having a biased portion having an outer diameter dimensioned to abut a wall of a pulmonary artery, an electrode coupled proximate the distal end. An implantable pulse generator is electrically coupled to the electrode. The implantable pulse generator is adapted to deliver a baroreflex stimulation signal to a baroreceptor in the pulmonary artery via the electrode. 
     One aspect includes a method. The method includes positioning an electrode on a distal end of a lead within a pulmonary artery, the distal end having a biased portion such that an outer diameter of the biased portion abuts a wall of the pulmonary artery, and delivering a baroreflex stimulation signal to a baroreceptor in the pulmonary artery via the electrode. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  shows a lead and pulse generator, in accordance with one embodiment. 
         FIG. 2  shows details of a heart. 
         FIG. 3  shows the lead of  FIG. 1  implanted in a heart, in accordance with one embodiment. 
         FIG. 4  shows a lead in accordance with one embodiment. 
         FIG. 5  shows the lead of  FIG. 4  with the distal end in a biased configuration. 
         FIG. 6  shows a lead in accordance with one embodiment. 
         FIG. 7  shows a side view of a lead in accordance with one embodiment. 
         FIG. 8  shows a portion of a lead in accordance with one embodiment. 
         FIG. 9  shows a lead implanted in accordance with one embodiment. 
     
    
    
     DETAILED DESCRIPTION 
     The following detailed description and accompanying drawings show specific embodiments in which the present invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention. Other embodiments may be utilized and structural changes may be made without departing from the scope of the present invention. 
     A brief discussion of hypertension and the physiology related to baroreceptors is provided to assist the reader with understanding this disclosure. This brief discussion introduces hypertension, the autonomic nervous system, and baroreflex. 
     Hypertension is a cause of heart disease and other related cardiac co-morbidities. Hypertension generally relates to high blood pressure, such as a transitory or sustained elevation of systemic arterial blood pressure to a level that is likely to induce cardiovascular damage or other adverse consequences. Hypertension has been arbitrarily defined as a systolic blood pressure above 140 mm Hg or a diastolic blood pressure above 90 mm Hg. Hypertension occurs when blood vessels constrict. As a result, the heart works harder to maintain flow at a higher blood pressure. Consequences of uncontrolled hypertension include, but are not limited to, retinal vascular disease and stroke, left ventricular hypertrophy and failure, myocardial infarction, dissecting aneurysm, and renovascular disease. 
     The automatic nervous system (ANS) regulates “involuntary” organs, while the contraction of voluntary (skeletal) muscles is controlled by somatic motor nerves. Examples of involuntary organs include respiratory and digestive organs, and also include blood vessels and the heart. Often, the ANS functions in an involuntary, reflexive manner to regulate glands, to regulate muscles in the skin, eye, stomach, intestines and bladder, and to regulate cardiac muscle and the muscle around blood vessels, for example. 
     The ANS includes, but is not limited to, the sympathetic nervous system and the parasympathetic nervous system. The sympathetic nervous system is affiliated with stress and the “fight or flight response” to emergencies. Among other effects, the “fight or flight response” increases blood pressure and heart rate to increase skeletal muscle blood flow, and decreases digestion to provide the energy for “fighting or fleeing.” The parasympathetic nervous system is affiliated with relaxation and the “rest and digest response” which, among other effects, decreases blood pressure and heart rate, and increases digestion to conserve energy. The ANS maintains normal internal function and works with the somatic nervous system. 
     The subject matter of this disclosure generally refers to the effects that the ANS has on the heart rate and blood pressure, including vasodilation and vasoconstriction. The heart rate and force is increased when the sympathetic nervous system is stimulated, and is decreased when the sympathetic nervous system is inhibited (e.g. when the parasympathetic nervous system is stimulated). 
     Baroreflex is a reflex triggered by stimulation of a baroreceptor. A baroreceptor includes any sensor of pressure changes, such as sensory nerve endings in the wall of the auricles of the heart, cardiac fat pads, vena cava, aortic arch and carotid sinus, that is sensitive to stretching of the wall resulting from increased pressure from within, and that functions as the receptor of the central reflex mechanism that tends to reduce that pressure. Additionally, a baroreceptor includes afferent nerve trunks, such as the vagus, aortic and carotid nerves, leading from the sensory nerve endings. Stimulating baroreceptors inhibits sympathetic nerve activity (stimulates the parasympathetic nervous system) and reduces systemic arterial pressure by decreasing peripheral vascular resistance. Baroreceptors are naturally stimulated by internal pressure and the stretching of the arterial wall. 
     Some aspects of the present subject matter locally and directly stimulate specific nerve endings in arterial walls rather than stimulate afferent nerve trunks in an effort to stimulate a desire response (e.g. reduced hypertension) while reducing the undesired effects of indiscriminate stimulation of the nervous system. For example, some embodiments stimulate baroreceptor sites in the pulmonary artery. Some embodiments of the present subject matter involve stimulating baroreceptor sites in the aorta. 
       FIG. 1  shows a lead  100  according to one embodiment. Lead  100  includes a flexible lead body  110  extending from a proximal end  115  to a distal end  120 . An electrode  130  is coupled proximate the distal end  120  of lead body  110 . The distal end  120  includes a biased portion  122 . Lead  100  is adapted to deliver stimulation to baroreceptors in the pulmonary artery. For example, the biased portion  122  can have a biased configuration having an outer diameter, D, dimensioned to abut a wall of a pulmonary artery to hold the electrode in place without any active fixation, as will be explained below. 
     Lead  100  is coupled to an implantable pulse generator  140 . Lead  100  includes conductors, such as coiled conductors that electrically couple pulse generator  140  to electrode  130 . Accordingly, implantable pulse generator  140  can deliver a baroreflex stimulation signal to a baroreceptor in the pulmonary artery via the electrode  130 . The lead further includes outer insulation to insulate the conductor. The system can include a unipolar system with the case acting as an electrode or a bipolar system with a pulse between two distally located electrodes. 
     In one embodiment, pulse generator  140  includes hardware, circuitry and software to perform NS functions. Some embodiments can also perform an AHT function. Pulse generator includes controller circuitry  142 . The controller circuitry  142  is capable of being implemented using hardware, software, and combinations of hardware and software. For example, according to various embodiments, the controller circuitry  142  includes a processor to perform instructions embedded in a memory to perform functions associated with NS therapy such as AHT therapy. In one example, the pulse generator delivers a pulse train having a frequency of between about 10 to 150 hertz via the electrode. In one embodiment, the pulse generator can deliver a waveform of 30 hertz, 2.5 msec, at 5 volts. Some embodiments deliver a waveform of 100 hertz, 1.0 msec, at 1, 3, or 5 volts, for example. 
       FIG. 2  shows a representation of a portion of a heart  200 . Heart  200  includes an aortic arch  203  and a pulmonary artery  204 . Pulmonary artery  204  includes a plurality of baroreceptors  206 . A lead, such as lead  100  ( FIG. 1 ), is capable of being intravascularly inserted through a peripheral vein and through the tricuspid valve into the right ventricle of the heart (not expressly shown in the figure) similar to a cardiac pacemaker lead, and continue from the right ventricle through the pulmonary valve  208  into the pulmonary artery  204 . 
     A portion of the pulmonary artery  204  and aorta arch  203  are proximate to each other. According to various aspects of the present subject matter, the baroreflex is stimulated in or around the pulmonary artery by at least one electrode intravascularly inserted into the pulmonary artery. Aspects of the present subject matter provide a relatively noninvasive surgical technique to implant a baroreceptor stimulator intravascularly into the pulmonary artery. The baroreceptors  206 , for example, are sensitive to stretching of the wall resulting from increased pressure from within. Activation of these nerve endings reduces pressure. 
     As illustrated, the pulmonary artery  204  includes a number of baroreceptors  206 , as generally indicated by the dark areas. Furthermore, a cluster of closely spaced baroreceptors  206 B is situated near the attachment of the ligamentum arteriosum  212 . According to various embodiments of the present subject matter, a lead is inserted through a peripheral vein and threaded through the tricuspid valve into the right ventricle, and from the right ventricle through the pulmonary valve  208  and into the pulmonary artery  204  to simulate baroreceptors in and/or around the pulmonary artery. In various embodiments, for example, the lead is positioned to stimulate the cluster of baroreceptors  206 B near the ligamentum arteriosum  212 . 
     There are also baroreceptor fields in the aortic arch  203 , near the ligamentum arteriosum  212 , and in the trunk  220  of the pulmonary artery  204 . Some embodiments position the lead in the pulmonary artery to stimulate baroreceptor sites in the aorta, possibly via the ligamentum arteriosum, or in the pulmonary trunk, or in either the right or left pulmonary arteries. 
       FIG. 3  shows a cross-section of electrode  130  mounted in pulmonary artery  204 , in accordance with one embodiment. In one embodiment, biased portion  122  includes an elongated spiral configuration with electrode  130  being a coiled electrode that is exposed to have substantially complete annular contact with the wall surface  304  of the pulmonary artery  204 . This allows for distributed stimulation along the length of the biased portion  122  and distributed wall fixation. Thus, for example, the entire electrode  130  can be an exposed electrode manufactured in a spiral configuration. As will be discussed below, some embodiments can include two or more discrete electrodes placed along the distal end of the lead. In some embodiments, portions of the surface of the electrode can be masked off to be electrically insulated. 
     As noted, the outer diameter of the biased portion  122  is designed to expand to abut the outer walls  304  of the pulmonary artery so as to fix the lead and the electrode in place by frictional forces. In this example, the electrode is adapted to be located near the ligamentum arteriosum  212  of the left pulmonary artery  204 . In some embodiments, at least a portion of electrode  130  can include a porous surface to further help fix the electrode within the artery. 
     In one embodiment, the biased portion  122  can have an outer biased diameter of about 10 mm to about 20 mm. Other embodiments can have a larger diameter. One example has a pitch of at least 5 coils per inch to provide high arterial surface contact and increased fixation. In general, the distal end and the electrode are dimensioned to optimize direct, low-voltage, high-frequency nerve stimulation. 
     In one embodiment, lead  100  can include a second electrode  312  located proximally from electrode  130 . This electrode can be used for bradyarrhythmia therapy, tachyarrhythmia therapy, as a sensing electrode, or as a cathode for electrode  130 . 
     In one example, electrode  130  is adapted to be chronically implanted in the pulmonary artery. For example, by passively mounting the electrode within the artery, no long-term damage is done to the artery. 
       FIGS. 4 and 5  show lead  100 , in accordance with one embodiment. Lead  100  can be implanted using a stylet  402  that is removed once the lead is positioned correctly. Removing stylet  402  from the lead allows distal end  122  to expand to its biased configuration until the electrode abuts the walls of the artery, as discussed above. 
       FIG. 6  shows a portion of a lead  600 , in accordance with one embodiment. Lead  600  includes a biased distal portion  622 , similar to biased portion  122  discussed above. In this embodiment, the biased portion  622  includes two or more discrete electrodes  624  exposed on the outer surface and outer diameter of the biased portion. In one embodiment, these discrete electrodes allow localized, but distributed stimulation when implanted in an artery. Alternatively, some of the discrete electrodes  624  can be coupled to a separate conductor of lead  600 . In this example, the user implants the electrode and then tests each electrode separately to discover which gives the best baroreflex response. Then, the non-productive electrode or electrodes can be turned off, or used only for sensing, or other purposes. In some embodiments, discrete electrodes  624  can be porous to provide further fixation within the artery. 
       FIG. 7  illustrates a baroreceptor stimulation lead  700  with an integrated pressure sensor  710  (IPS), according to various embodiments of the present subject matter. Lead  700  can include an IPS  710  with a baroreceptor stimulator electrode to monitor changes in blood pressure, and thus to monitor the effect of the baroreceptor stimulation. In various embodiments, micro-electrical mechanical systems (MEMS) technology can be used to sense the blood pressure. Some sensor embodiments determine blood pressure based on a displacement of a membrane. 
     In one example use of lead  700 , a system can include baroreceptor stimulation circuitry and sensor circuitry. The circuitry can be within pulse generator  140  ( FIG. 1 ) or be a separate system communicating wirelessly with the pulse generator. One or more leads can be connected to the sensor circuitry and baroreceptor stimulation circuitry. The baroreceptor stimulation circuitry is used to apply electrical stimulation pulses to desired baroreceptors sites, such as baroreceptor sites in the pulmonary artery, through one or more stimulation electrodes, such as electrode  130  on biased portion  722 . The sensor circuitry is used to detect and process ANS nerve activity and/or surrogate parameters such as blood pressure, respiration and the like, to determine the ANS activity. 
     Lead  700 , for example, is capable of being intravascularly introduced to stimulate a baroreceptor site, such as the baroreceptor sites in the pulmonary artery, aortic arch, or ligamentum arteriosum. One or more additional electrodes can be provided to pace and/or sense cardiac activity, such as that which may occur within the right ventricle with the sensor  710  located in or near the pulmonary artery and programmed to stimulate and sense, either directly or indirectly through surrogate parameters, baroreflex activity. 
       FIG. 8  shows a lead  800  according to one embodiment, lead  800  includes a distal portion  820  including a biased circular portion  822 . In this embodiment, a plurality of discrete electrodes  824  are placed around the outer circumference of the circular portion  822 . In other embodiments, the entire biased circular portion can be an exposed electrode. Circular biased portion  822  is dimensioned to fixate the distal end  820  within the pulmonary artery. For example, the biased circular portion can have an outer diameter of between 10 mm and 20 mm. In one embodiment, the circular plane of the distal portion  820  of the lead  800  is perpendicular to the long axis  830  of the lead body (i.e. shaped like a lasso). A distal end fashioned in this way tends to stimulate the pulmonary artery in a plane or cross section of the artery. Other embodiments can use other angles as needed. 
     To provide hypertension therapy according to one embodiment, a lead, such as any of the leads discussed herein, is intravascularly inserted through a peripheral vein and through the tricuspid valve into the right ventricle of the heart and then from the right ventricle through the pulmonary valve into the pulmonary artery. An electrode on the lead is fixated to a region of the pulmonary artery having one or more baroreceptors. One example passively fixates the electrode proximate the ligamentum arteriosum of the left pulmonary artery. In one embodiment, the pulse generator designed to intermittently pace with low-voltage, high frequency pulse train. For example, one embodiment delivers at least a 10 hertz pulse train via the electrode. As noted above, in some embodiments the pulse generator can deliver a waveform of 30 hertz, 2.5 msec, at 5 volts. Some embodiments deliver a waveform of 100 hertz, 1.0 msec, at 1, 3, or 5 volts, for example. In some embodiments, the baroreceptor can be intermittently paced for about 5 to 10 seconds each minute at a voltage of about 0.1 volts to 10 volts and a frequency between about 10 Hz and 150 Hz. Some examples utilize a voltage between about 1 volt to about 10 volts. 
     The leads of the present subject matter are easy to implant and deliver uncomplicated waveforms. Moreover, the baroreceptor pacing response is immediate and reversible. 
     Further embodiments can include a sensor to monitor blood pressure. The sensor can sense a physiological parameter regarding an efficacy of the baroreflex therapy and provides a signal indicative of the efficacy of the baroreflex therapy. For example, a controller can be connected to a pulse generator to control the baroreflex stimulation signal and to the sensor to receive the signal indicative of the efficacy of the baroreflex therapy. In some examples, the pulse generator can be further adapted to generate a cardiac pacing signal, and the lead can include a second electrode to be positioned to deliver the cardiac pacing signal to capture the heart. The present lead allows for chronic indwelling and is easy to implant. 
     In various embodiments of baroreceptor pacing according to the present subject matter, the system can deliver the pulse train intermittently with no sensing, or the system can be activated by the user when the user is at rest, or it can be activated by a timer to be periodically turned off and on, or it can be activated when the user goes to sleep, for example. 
     According to various embodiments, the stimulator circuitry of the pulse generator can include one or more functions as described in the commonly assigned U.S. patent application filed on the same date as the present application and incorporated by reference in its entirety: “Baroreflex Stimulation System to Reduce Hypertension,” Ser. No. 10/746,134, filed on Dec. 24, 2003. 
     For example, various embodiments of the present subject matter relate to baroreflex stimulator systems. Such baroreflex stimulation systems are also referred to herein as neural stimulator (NS) devices or components. Examples of neural stimulators include anti-hypertension (AHT) devices or AHT components that are used to treat hypertension. Various embodiments of the present subject matter include stand-alone implantable baroreceptor stimulator systems, include implantable devices that have integrated NS and cardiac rhythm management (CRM) components, and include systems with at least one implantable NS device and an implantable CRM device capable of communicating with each other either wirelessly or through a wire lead connecting the implantable devices. Integrating NS and CRM functions that are either performed in the same or separate devices improves aspects of the NS therapy and cardiac therapy by allowing these therapies to work together intelligently. 
     Thus, various embodiments of the present subject matter provide an implantable NS device that automatically modulates baroreceptor stimulation using an IPS. Integrating the pressure sensor into the lead provides localized feedback for the stimulation. This localized sensing improves feedback control. For example, the integrated sensor can be used to compensate for inertia of the baroreflex such that the target is not continuously overshot. According to various embodiments, the device monitors pressure parameters such as mean arterial pressure, systolic pressure, diastolic pressure and the like. As mean arterial pressure increases or remains above a programmable target pressure, for example, the device stimulates baroreceptors at an increased rate to reduce blood pressure and control hypertension. 
     As 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. A NS device having an IPS is able to automatically modulate baroreceptor stimulation, which allows an implantable NS device to determine the level of hypertension in the patient and respond by delivering the appropriate level of therapy. However, it is noted that other sensors, including sensors that do not reside in an NS or neural stimulator device, can be used to provide close loop feedback control. 
     An aspect of the present subject matter relates to a chronically-implanted stimulation system specially designed to treat hypertension by monitoring blood pressure and stimulating baroreceptors to activate the baroreceptor reflex and inhibit sympathetic discharge from the vasomotor center. Baroreceptors are located in various anatomical locations such as the carotid sinus and the aortic arch. Other baroreceptor locations include the pulmonary artery, including the ligamentum arteriosum, and sites in the atrial and ventricular chambers. In various embodiments, the system is integrated into a pacemaker/defibrillator or other electrical stimulator system. Components of the system include a high-frequency pulse generator, sensors to monitor blood pressure or other pertinent physiological parameters, leads to apply electrical stimulation to baroreceptors, algorithms to determine the appropriate time to administer stimulation, and algorithms to manipulate data for display and patient management. 
     Various embodiments relates to a system that seeks to deliver electrically mediated NS therapy, such as AHT therapy, to patients. Various embodiments combine a “stand-alone” pulse generator with a minimally invasive, unipolar lead that directly stimulates baroreceptors in the vicinity of the heart, such as in the pulmonary artery. This embodiment is such that general medical practitioners lacking the skills of specialist can implant it. Various embodiments incorporate a simple implanted system that can sense parameters indicative of blood pressure. This system adjusts the therapeutic output (waveform amplitude, frequency, etc.) so as to maintain a desired quality of life. In various embodiments, an implanted system includes a pulse generating device and lead system, the stimulating electrode of which is positioned near endocardial baroreceptor tissues using transvenous implant technique(s). 
     Another embodiment includes a system that combines NS therapy with traditional bradyarrhythmia, tachyarrhythmia, and/or congestive heart failure (CHF) therapies. Some embodiments use an additional “baroreceptor lead” that emerges from the device header and is paced from a modified traditional pulse generating system. In another embodiment, a traditional CRM lead is modified to incorporate proximal electrodes that are naturally positioned near baroreceptor sites. With these leads, distal electrodes provide CRM therapy and proximal electrodes stimulate baroreceptors. 
     For example,  FIG. 9  schematically shows an unbiased lead  900  having an electrode  910  on a distal end and an active or positive fixation mechanism, such as a helix  920 . Electrode  910  is intended to be implanted at or near a site of high baroreceptor concentration, such as baroreceptor site  206 B in the pulmonary artery  204 . At implant, lead  900  would be passed through the heart and into the pulmonary artery. With the distal end of lead  900  generally straight (unbiased), the act of implantation would naturally position the distal electrode end  910  at or near baroreceptor site  206 B. Stimulation at the  206 B location by a single electrode can be preferable, in some instances, to advancing a longer lead device deeper into the pulmonary artery to attempt stimulation of a number of diffuse locations. 
     Various embodiments of the present subject matter relate to a method of sensing atrial activation and confining pulmonary artery stimulation to the atrial refractory period, preventing unintentional stimulation of nearby atrial tissue. An implantable baroreceptor stimulation device monitors atrial activation with an atrial sensing lead. A lead in the pulmonary artery stimulates baroreceptors in the vessel wall. However, instead of stimulating these baroreceptors continuously, the stimulation of baroreceptors in the pulmonary artery occurs during the atrial refractory period to avoid capturing nearby atrial myocardium, maintaining the intrinsic atrial rate and activation. Various embodiments of the present subject matter combine an implantable device for stimulating baroreceptors in the wall of the pulmonary artery with the capability for atrial sensing. Various embodiments stimulate baroreceptors in the cardiac fat pads, in the heart chambers, and/or afferent nerves. 
     For example, the pulse generator can include a transceiver and associated circuitry for use to communicate with a programmer or another external or internal device. Various embodiments have wireless communication capabilities. For example, some transceiver embodiments use a telemetry coil to wirelessly communicate with a programmer or another external or internal device. 
     The above description is intended to be illustrative, and not restrictive. Many other embodiments will be apparent to those of skill in the art upon reviewing the above description. The scope of the invention should, therefore, be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.