SYMPATHETIC NERVE STIMULATION FOR POST TACHYCARDIA SYNDROME AND POSTURAL ORTHOSTATIC HYPOTENSION
TECHNICAL FIELD
[0001] This disclosure is directed to systems and methods of stimulating sympathetic nerves to reduce or eliminate symptoms of post tachycardia syndrome and postural orthostatic hypotension.
BACKGROUND
[0002] Postural tachycardia syndrome (POTS) is a debilitating condition that causes a number of symptoms when a person transitions from lying down to standing up, including an increased heart rate, dizziness and fatigue. Currently, the treatment for POTS includes lifestyle changes (diet, exercise, sleep) or medications, and these treatments are not always effective. Although POTS doesn’t impact life expectancy, it can severely disrupt daily living for people living with the syndrome. It is estimated that in the U.S. up to 1.3 million people suffer from POTS, with 0.2% prevalence in the general population. The exact cause of POTS remains unclear, though currently it is believed that there may be multiple causes.
[0003] Orthostatic hypotension (OH) is a sudden drop in blood pressure when a person stands from a seated or prone (lying down) position. The person may experience dizziness and may even faint.
[0004] Healthcare providers define orthostatic hypotension based on an individual’s normal blood pressure and the experienced change in blood pressure that results when the individual stands. A person can be diagnosed with orthostatic hypotension if their blood pressure drops more than 20 millimeters of mercury in systolic pressure or 10 millimeters of mercury in diastolic pressure within three minutes of standing up.
[0005] Persistent orthostatic hypotension can cause serious complications, especially in older adults. Typical complications include:
Falls - often as a result of fainting;
Stroke - swings in blood pressure from standing and sitting as a result of orthostatic hypotension can be a risk factor for stroke due to a reduction in blood supply to the brain;
Cardiovascular diseases - orthostatic hypotension can be a risk factor for cardiovascular diseases and complications, such as chest pain, heart failure or heart rhythm problems.
[0006] In view of these complications, systems and methods of preventing or at minimum mitigating the effects of both POTS and OH are desired. SUMMARY
[0007] One aspect of the disclosure is directed to a therapeutic system also including an implantable stimulation signal generator. The system also includes a pair of electrodes in electrical communication with the implantable signal generator, where the pair of electrodes are configured for placement proximate sympathetic nerves of a patient; and a motion sensor in communication with the implantable stimulation signal generator, where upon detection of motion of a patient in excess of a threshold the implantable stimulation signal generator is configured to output a stimulation signal to the electrodes, where the stimulation signal is configured to stimulate nerves to cause a blood vessel to contract. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.
[0008] Implementations of this aspect of the disclosure may include one or more of the following features. The therapeutic system where the motion sensor includes an accelerometer or a gyroscope. The pair of electrodes include screw type electrodes configured to screw into a blood vessel wall. The pair of electrodes are coupled to the implantable stent. Expansion of the balloon catheter expands the stent to contact a wall of the blood vessel. The electrodes are configured for placement proximate a spinal nerve. The electrodes are configured for placement proximate spinal nerves located between tl2 and upper lumbar vertebrae. The electrodes are configured for placement proximate a dorsal root area of a patient. Contraction of the blood vessel increases a blood pressure of a patient. The increase in blood pressure counters a drop in blood pressure experienced by a patient due to the detected motion in excess of a threshold. The drop in blood pressure is related to a patient condition including post tachycardia syndrome and postural orthostatic hypotension. The signal output to the electrodes includes a biphasic signal. The signal output to the electrodes includes a bipolar signal. The therapeutic system is configured to detect a heart rate sensed via the electrodes. The signal output to the electrodes is triggered by a combination of the detected heart rate and the detected motion in excess of the threshold. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions. [0009] A further aspect of the disclosure is directed to a method of treating a condition. The method includes detecting a motion of a patient; and outputting a stimulation signal from a generator to an electrode located proximate a sympathetic nerve of a patient, where the output signal to the electrodes stimulates the sympathetic nerves causing a blood vessel to contract, where the contraction of the blood vessel increases a blood pressure of the patient. Other embodiments of this aspect include corresponding computer systems, apparatus, and computer programs recorded on one or more computer storage devices, each configured to perform the actions of the methods and systems described herein.
[0010] Implementations of this aspect of the disclosure may include one or more of the following features. The method further including detecting a heart rate of the patient. Outputting the stimulation signal is based on the detected motion and the detected heart rate. The electrode proximate the sympathetic nerve is placed within a blood vessel of the patient. The electrode is proximate spinal nerves located between 112 and upper lumbar vertebrae or proximate a dorsal root area of a patient. Implementations of the described techniques may include hardware, a method or process, or computer software on a computer-accessible medium, including software, firmware, hardware, or a combination of them installed on the system that in operation causes or cause the system to perform the actions. One or more computer programs can be configured to perform particular operations or actions by virtue of including instructions that, when executed by data processing apparatus, cause the apparatus to perform the actions.
[0011] Further disclosed herein is a therapeutic system and method including an implantable stimulation signal generator, a pair of electrodes in electrical communication with the implantable signal generator, the pair of electrodes being configured for placement proximate sympathetic nerves of a patient, and a motion sensor in communication with the implantable stimulation signal generator, wherein upon detection of motion of a patient in excess of a threshold the implantable stimulation signal generator is configured to output a stimulation signal to the electrodes, wherein the stimulation signal is configured to stimulate nerves to causing a blood vessel to contract.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Various aspects and embodiments of the disclosure are described hereinbelow with references to the drawings, wherein:
[0013] FIG. 1 is a schematic diagram of balloon catheter assembly in accordance with some examples of the disclosure;
[0014] FIG. 2A depicts a stimulation system implanted in a patient in accordance with some examples of the disclosure; [0015] FIG. 2B depicts a schematic view of a generator in accordance with some examples of the disclosure;
[0016] FIG. 3 is a flow diagram of a method in accordance with some examples of the disclosure;
[0017] FIG. 4 is a perspective view of screw-type electrode in accordance with some examples of the disclosure;
[0018] FIG. 5 is a perspective view of a mapping system in accordance with some examples of the disclosure;
[0019] FIG. 6 is a schematic view of a mapping system in accordance with some examples of the disclosure; and
[0020] FIG. 7 is a perspective view of a mapping catheter in accordance with some examples of the disclosure.
DETAILED DESCRIPTION
[0021] This disclosure is directed to therapeutic systems and methods for stimulating sympathetic nerves to achieve a temporary increase in blood pressure of the patient. The temporary increase in blood pressure may offset or eliminate the blood pressure drop associated with POTS or OH. In accordance with one aspect of the disclosure, stimulation electrodes may be placed, for example, in the inferior vena cava or the left or right renal vein proximate the aorticorenal ganglia. Alternatively, the stimulation electrodes may be placed proximate the dorsal root ganglia. In yet a further aspect of the disclosure, stimulation is applied via spinal cord stimulation with placement of a spinal cord stimulation lead in the lower thoracic spine (e.g., T12) through the upper lumbar vertebrae or in the dorsal root area.
[0022] A generator electrically connected to the electrodes provides stimulation energy to the electrodes, for example a bi-phasic stimulation signal or alternatively a bipolar stimulation signal. The generator may be implanted in the patient. A gyroscope or accelerometer within the generator may be configured to detect movements of the patient in which the generator and electrodes are implanted. Upon detection of movement of the patient (e.g., movement consistent with moving from sitting or lying to standing), and prior to the patient experiencing a drop in blood pressure that is associated with POTS or OH, the generator may be configured to apply stimulation to the patient via the electrodes. Application of the stimulation signal to the patient at the implanted location result in stimulation of the sympathetic nerves proximate the electrodes. This stimulation of the sympathetic nerves may result in contraction of muscle fibers in the blood vessels in which the electrodes are implanted or in the blood vessels along which the stimulated sympathetic nerves run. The stimulation may be applied for a predetermined period of time (e.g., 15 seconds) or until another physiological indicator (e.g., heart rate) indicates that the effects of POTS or OH associated with a drop in blood pressure have been compensated for and that stimulation may cease. These and other aspects of the disclosure are described herein below.
[0023] POTS can be characterized in at least three forms. Neuropathic POTS is a mild form of peripheral autonomic neuropathy characterized by the inability of the peripheral vasculature (especially the nervous system) to maintain adequate vascular resistance in the face of gravitational stress. This leads to a much greater than normal degree of blood pooling in the dependent areas of the body (legs, lower arms, and the mesenteric vasculature) while upright. The sequestration of blood away from the central vasculature elicits a compensatory increase in heart rate and myocardial contractility in an attempt to maintain cerebral perfusion at constant levels. Whereas the increase in heart rate may initially be compensatory, the extent of peripheral venous pooling can continue to increase over time and exceed this compensatory effect.
[0024] Hyperadrenergic POTS patients often describe a more gradual and progressive emergence of symptoms over time rather than an abrupt onset. Patients with hyperadrenergic POTS often complain of significant tremor, anxiety, and cold sweaty extremities while upright. A characteristic of this form of POTS is that patients will often display orthostatic hypertension in addition to orthostatic tachycardia.
[0025] Hypovolemic POTS patients suffer from reduced blood volume and is a condition that can overlap with neuropathic & hyperadrenergic POTS.
[0026] As noted above, stimulation of the sympathetic nervous system may cause a temporary increase in blood pressure. This is thought to be from stimulation of the afferent nerves and an increase in the sympathetic tone of the blood vessels associated with the nerves receiving the stimulation. By changing sympathetic tone, neuropathic POTS and orthostatic hypotension patients’ symptoms can be reduced or eliminated by reducing the impact of blood pooling in lower body or periphery of the patient. In accordance with the disclosure, by having an implant, such as a motion sensor, interacting with a stimulator, stimulus is provided to the sympathetic nervous system at times of postural change. In accordance with the disclosure, there are number of locations that may be suitable for stimulation. As an example, the aorticorenal ganglia can be stimulated from within the interior vena cava (IVC) with associated stimulus of afferent sympathetic nerves. As described further below, this aspect of the disclosure requires placement of an implantable electrode configuration in the IVC and subsequent placement of the stimulation generator subcutaneously. As an alternative, stimulation of the dorsal root ganglia may have a similar impact and have beneficial electrode durability/power requirements. However, implantation may prove more challenging.
[0027] Fig. 1 depicts a catheter deployed stent assembly in accordance with some examples of the disclosure. The assembly includes a balloon catheter 5 having a distal end 10, an inflatable balloon 12, an intermediate portion 14 and a shaft 16. Shaft 16 extends all the way to the proximal end of the catheter 5 and includes an appropriate fitting or hub assembly 18 for connection to a handle 19, which is configured to enable application of dilation pressure and admitting a guide wire 20 which extends through the catheter 5 and out of distal end 10.
[0028] The shaft 16 may include an inner tube 11 which runs the entire length of the catheter 5. In some examples, the inner tube 11 may define a first lumen and a second lumen. Tube 11 may be made of any number of materials, such as polyethylene or another biocompatible polymer. The first lumen of inner tube 11 may be configured to receive a guide wire 20 in use so that the catheter 5 can be advanced over the guide wire 20 to the site of interest. In some examples, the first lumen extends the length of the inner tube 11 and catheter 5 may be an over the wire (OTW) catheter. In other examples, the second lumen may extend for part of a distal portion of the inner tube 11 and the catheter 5 may be a rapid exchange (RX) catheter. The second lumen is the inflation lumen for balloon 12 and is arranged to enable pressurization of the balloon.
[0029] The assembly also includes a hollow outer tube or catheter sheath 24 of sufficient inside diameter to receive the catheter 5. As shown in Fig. 1, the balloon 12 is positioned within sheath 24. Sheath 24 can be made of any suitable material, typically a plastic such as polyethylene or another biocompatible polymer.
[0030] A stent 22 is carried within the catheter sheath 24 distal of the distal end 10 of the catheter 5 in a coaxial arrangement. The stent 22 includes two or more electrodes 26. The catheter sheath 24, is configured for navigation within the patient, for example by accessing, for example, the saphenous or femoral vein and advancing the catheter sheath 24, catheter 5, and stent 22 over the guide wire 20 to a desired location within the patient. Once so positioned, the stent 22 may be advanced from the catheter sheath 24 by advancement of the catheter 5 and the balloon 12. With the positioning confirmed using imaging such as fluoroscopy, computed tomography, or ultrasound imaging modalities, the balloon 12 is expanded within the stent 22 until the stent 22 takes on its final form contacting the walls of the blood vessel in which it is located. In accordance with this disclosure, the electrodes 26 on the stent 22 are in contact with the blood vessel wall, as described herein below. [0031] Fig. 2 depicts a stent 22 placed in a blood vessel 50 of a patient. Fig. 2 depicts two stents 22, once placed in the IVC and one placed in the left renal vein (LRV). These two stents 22 are presented here as alternatives, and those of skill in the art will recognize that both stents 22 are not required to perform the methods of this disclosure. The positioning of the stent 22 can be determined based on a mapping process described in greater detail below. Once so placed, the stent 22 and particularly the electrodes 26 can be electrically connected to a generator or stimulator 28. The stent 22 may include any number of electrodes 26, such as at least two electrodes 26 or a plurality of electrodes 26 around the circumference of the stent 22, but only two electrodes are needed for stimulation. The generator 28 is similar to a pacemaker or defibrillator used to stimulate the heart muscle and is configured to provide stimulation signals to the electrodes 26. The generator 28 may be surgically placed at a sub-cutaneous location and a connector lead 30 may connect the electrodes 26 with the generator 28. The connector lead 30 may be tunneled through a subcutaneous layer of tissue to connect the electrodes 26 and the generator 28.
[0032] By placement of the stent 22 and the electrodes 26 in the IVC, stimulation applied to the blood vessel from the generator 29 through the electrodes 26 in contact with the blood vessel wall can result in stimulation of the aorticorenal ganglia (ARG), which is proximate the IVC. Stimulation of the ARG may result in a temporary increase in blood pressure of a patient during the stimulation.
[0033] As noted above, the stent 22 may alternatively be placed in the left renal vein or right renal vein, which run adjacent to the left renal artery and right renal artery, respectively. Application of stimulation to the blood vessel walls of the renal vein results in stimulation of the sympathetic nerves of the adjacent renal artery. Stimulation of the sympathetic nerves of the renal artery has been shown to result in a temporary increase in blood pressure of a patient during the stimulation. In some examples, a first stent 22 may be placed in the IVC and a second stent 22 may be placed in the left renal vein or right renal vein.
[0034] Stimulation of the sympathetic nerves adjacent a blood vessel causes contraction of smooth muscle cells or other muscle fibers within the blood vessel. The contraction of the muscle cells or fibers effectively reduces the diameter of the blood vessel through which blood flows, resulting in an increase in vascular resistance and effectively increasing the blood pressure of patient. The increase in blood pressure reduces the likelihood of an increase in heart rate to compensate for POTS or OH, thus placing less stress on the heart and vasculature as a result of a sudden increase in heart rate. In addition, venous pooling may also decrease, in part due to the reduced flow of blood as a result of the increased vascular resistance. The reduced vascular pooling may further assist in maintaining the blood pressure of the patient.
[0035] Though depicted as including a plurality of electrodes 26, the stent 22 may only require a single pair of electrodes 26 to deliver bipolar stimulation. Where more than two electrodes 26 are included on the stent 22, a test may be performed by energizing various pairs of electrodes and assessing the blood pressure response each pair elicits. Whichever pair of electrodes 26 achieved the greatest blood pressure response may then be identified as the pair of electrodes 26 to be energized for further abatement of symptoms associated with POTS or OH. Where more than two electrodes 26 are employed, the electrodes may be placed circumferentially and/or longitudinally about the stent 22.
[0036] The generator 28 is configured to output the stimulation signal to the electrodes 26. The stimulation signal may be, for example, a biphasic direct current (DC) pulse with an amplitude of between 1mA and 20mA, a pulse width of between 2 and 10 ms and a frequency of between 5 and 50Hz. As shown in Fig. 2B, to generate and output the stimulation signal to the leads 30 the generator includes a battery 40, a processor 42, wireless communications module 44, a motion sensor 46, a memory 47 and a signal generator 48. The signal generator 48 is in communication with the leads 30 and thus the electrodes 26. The motion sensor 46 may include an accelerometer configured to measure linear acceleration or a gyroscope configured to measure angular velocity or both.
[0037] As described briefly above, the generator 28 and electrodes 26 are configured to operate autonomously following implantation in the patient. In accordance with some examples of the disclosure, the autonomous operation is described in connection with method 300 in Fig. 3. At step 302, following implantation, the generator 28 receives an initiation signal from an external programmer (not shown) via the wireless communications module 44. The external programmer may be similar to those used for communications with pacemakers and can be employed to program the generator 28 for one or more selected stimulation protocols (e.g., different amperages, pulse duration, frequency, etc.). In addition, the programmer can be employed to turn the generator 28 on. At step 304, a self-diagnostic application stored in the memory 47 may be optionally performed by the processor 42 of the generator 28 to confirm electrical communication with the electrodes 26, motion sensor 46, and other components in the generator 28. At step 306, the generator 28 may apply a test stimulation to the electrodes 26. The effects of the test stimulation on the patient’s blood pressure can be detected at step 308. This detection may be via an external device separate from the generator 28. If at step 310 the test stimulation results in a change in blood pressure within a threshold range (e.g., greater than a 10 mm Hg increase but less than 30 mm Hg increase), the value of the test stimulation can be stored in the memory 47 of the generator 28 as the initial therapy stimulation at step 311. If not, an application stored in the memory 47 and executed by the processor 42 may alter the attributes of the test stimulation at step 312 (e.g., increase or decrease amperage, increase or decrease pulse duration, increase or decrease frequency) and the method returns to step 306. Once an initial therapy stimulation is stored in the memory at step 311, the patient may be directed to move from a laying position to a standing position. The motion sensor 46 (e.g., gyroscope and/or accelerometer within the generator 28) detects the posture change using either acceleration or velocity and signals the generator 28 at step 314 to cause the signal generator 48 to deliver a stimulation signal to the electrodes 26 at step 316. At step 318, the blood pressure of the patient is again observed via an external device separate from the generator 28. At step 320, an application stored in the memory 47 and executed by the processor 42 determines whether the change in blood pressure as a result of standing is less than a threshold (e.g., 5 mm Hg). If yes, the application sets the initial therapy stimulation for output by the signal generator 48 as the final therapy stimulation setting in the memory 47. However, if not, the method returns to step 312 where the application stored in the memory 47 alters the stimulation signal again. This process is repeated until the change in blood pressure as a result of moving from sitting to standing is below the threshold at step 320. This sets the value of the stimulation signals applied by the signal generator 48 to the electrodes 26 based on the detected changes of the patient’s orientation. As will be appreciated, if the patient begins to suffer the symptoms of POTS or OH (e.g., light headedness, fainting, etc.), the parameters of the stimulation signal may again be adjusted using the programmer.
[0038] Though described as being triggered by just the sensed motion (e.g., from the accelerometer or gyroscope), other inputs to the processor 42 in the generator 28 may be employed as well. For example, the heart rate of the patient may be detected using the electrodes 26 on the stent 22 and a further application stored in the memory 47 and executed by the processor 42. The detected heart rate may be used in combination with the detected motion from the motion sensor 46 (e.g., accelerometer of gyroscope) to provide the input to the generator 28 regarding when to output a stimulation signal to the electrodes 26. For example, as noted above, to compensate for a drop in blood pressure, the patient’s heart rate is likely to increase. Thus, when generator 28 detects a change in position coupled with a detected increase in heart rate, the processor 42 may be configured in combination with an application stored in the memory 47 to recognize the combination as a trigger to start output the stimulation signal to the electrodes 26. Alternatively, an external device such as a smart watch or other device may detect the heart rate and communicate the heart rate to the generator 28 for use as described herein above.
[0039] In accordance with the disclosure, the stimulation may be applied for a set duration (e.g., 10-20 seconds). Additionally or alternatively, the generator 28 may be configured to assess a physiological parameter and when the physiological parameter reaches a threshold value, the generator 28 may cease outputting the stimulation signal. For example, the generator 28 may be configured to detect a return to a normal heart rate and cease application of stimulation.
[0040] In accordance with a further aspect of the disclosure, through the electrodes 26 are described hereinabove as being formed on or coupled to a stent 22, the disclosure is not so limited. For example, as depicted in FIG. 4, the electrode 26 may be a screw type electrode. The electrode 26 may be navigated to a desired location in the vasculature (e.g., the IVC or the left or right renal veins) where the electrode 26 can be screwed into the blood vessel. Again, a lead 30 connects the screw-in electrodes 26 to the generator 28 and is used as described herein above.
[0041] FIG. 5 illustrates a mapping system in accordance with the disclosure and generally identified by reference numeral 100. As will be described in further detail hereinbelow, the mapping system 100 enables navigation of a mapping catheter 150 to a desired location within the patient’s anatomy (e.g., the IVC or a renal vein), delivery of neurostimulation to tissue, observing a physiological response to the application of neurostimulation to the tissue (e.g., change in blood pressure), if necessary adjustment of a position of the mapping catheter 150 based upon the physiological response, reapplication of the neurostimulation to the tissue at the adjusted position, and mapping of the locations in which the physiological response is greatest, or in excess of a threshold.
[0042] The mapping system 100 includes a workstation 120, the mapping catheter 150 operably coupled to the workstation 120, and an imaging device 170, which may be operably coupled to the workstation 120. The patient “P” is shown lying on an operating table 112 with the mapping catheter 150 inserted through a portion of the patient’s femoral vein, although it is contemplated that the mapping catheter 150 may be inserted into any suitable portion of the patient’s vascular network that is in fluid communication with a desired blood vessel for mapping. Further, the mapping catheter 150 may employ a guidewire or a guide catheter 158 (FIG. 7) without departing from the scope of the disclosure. [0043] Continuing with FIG. 5 and with additional reference to FIG. 2, the workstation 120 may include a computer 122, a stimulation source 124 operably coupled to the computer 122, and a stimulation source 124 operably coupled to the computer 122.
[0044] The computer 122 is coupled to a display 126 that is configured to display one or more user interfaces 128 output by the computer 122. The computer 122 may be a desktop computer or a tower configuration with display 126 or may include a laptop computer or other computing device. The computer 122 includes a processor 130 which executes software stored in a memory 132. The memory 132 may store one or more applications 134 and/or algorithms 144 to be executed by the processor 130. A network interface 136 enables the workstation 120 to communicate with a variety of other devices and systems via the internet. The network interface 136 may connect the workstation 120 to the Internet via a wired or wireless connection. Additionally, or alternatively, the communication may be via an ad hoc Bluetooth® or wireless network enabling communication with a wide-area network (WAN) and/or a local area network (LAN). The network interface 136 may connect to the Internet via one or more gateways, routers, and network address translation (NAT) devices. The network interface 136 may communicate with a cloud storage system 138, in which further data, image data, and/or videos may be stored. The cloud storage system 138 may be remote from or on the premises of the hospital such as in a control or hospital information technology room. It is envisioned that the cloud storage system 38 could also serve as a host for more robust analysis of acquired images (e.g., fluoroscopic, computed tomography (CT), magnetic resonance imaging (MRI), cone-beam computed tomography (CBCT), etc.), data, etc. (e.g., additional or reinforcement data for analysis and/or comparison). An input module 140 receives inputs from an input device such as a keyboard, a mouse, voice commands, an energy source controller (e.g., a foot pedal or handheld remote-control device that enables the clinician to initiate, terminate, and optionally, adjust various operational characteristics of the stimulation source 124. An output module 142 connects the processor 130 and the memory 132 to a variety of output devices such as the display 126. In embodiments, the display 126 may be a touchscreen display.
[0045] The stimulation source 124 generates a stimulation signal, for example a biphasic waveform at an energy level such that the stimulation generated by the stimulation source 124 does not denervate the target tissue. Rather, the stimulation source 124 generates a stimulation signal capable of effectuating a response from the nerves indicative of tissue that would be a candidate for stimulation to provide therapy for patients suffering from POTS or OH. Responses to stimulation may include an increase in blood pressure, an increase in vessel stiffness, changes in pulse wave velocity, augmentation pressure, heart rate variability, etc., and combinations of these. In one example, the stimulation source 124 generates a biphasic waveform where a leading phase of each successive pulse of the biphasic waveform is switched or otherwise inverted. In this manner, a biphasic waveform having an initial pulse with an anodal leading phase and a cathodal trailing phase is followed by a second pulse with a cathodal leading phase and an anodal trailing phase which will be followed by a third pulse returning to an anodal leading phase and a cathodal trailing phase, and so on. Alternatively, a biphasic waveform having an initial pulse with a cathodal leading phase and an anodal trailing phase may be followed by a second pulse with an anodal leading phase and a cathodal trailing phase which will be followed by a third pulse returning to a cathodal leading phase and an anodal trailing phase. As can be appreciated, the leading phase of each pulse of the biphasic waveform may be alternated for the duration of the application of neurostimulation to the target tissue.
[0046] As noted above, the amplitude, frequency, pulse width, and/or duration of the stimulation can be selected and/or modified to ensure neurostimulation of the sympathetic nerves of the blood vessel without damaging the blood vessel or the nerves within or surrounding the blood vessel or causing excess vasoconstriction about the mapping catheter 150 (e.g., inhibiting the movement of the mapping catheter 150 within the blood vessel). A pulse duration (pulse width) may be modified to ensure that anodic stimulation of the tissue is maintained as at certain pulse durations regions of anodic stimulation may dissipate or otherwise disappear resulting in reduced stimulation effect. In one non-limiting embodiment, the stimulation source 124 generates biphasic waveforms having a frequency of between approximately 10 - 30Hz, a voltage of between approximately 5 - 30 V, a current of between approximately 2 - 500 mA, and a pulse width of between approximately 2 - 10 ms. It is envisioned that in embodiments where unmyelinated nerve fibers are targeted, the pulse width of the biphasic waveform may be between approximately 2-120 ms. In a further example, the stimulation parameters are a constant current of 20mA for a blood vessel branches and 30 mA for main blood vessels, a pulse width of 5 mS, a frequency of approximately 20 Hz and a duration of between 10 and 60 seconds.
[0047] FIG. 7 depicts one embodiment of a mapping catheter 150 in accordance with the disclosure. The mapping catheter 150 includes an elongated shaft 152 having a handle (151 Fig. 5) disposed on a proximal end portion of the elongated shaft 152. The mapping catheter 150 includes an energy delivery assembly 154 at which one or more electrodes 156 are located. The elongated shaft 152 of the mapping catheter 150 is configured to be advanced within a portion of the patient’s vasculature, such as a renal vein or the IVC or another suitable portion of patient’s vascular network that is in fluid communication with the patient’s renal artery. In embodiments, the energy delivery assembly 154 is configured to be transformed from an initial, undeployed configuration having a generally linear profile, to a second, deployed or expanded configuration, where the energy delivery assembly 154 forms a generally spiral and/or helical configuration for delivering energy to a site for application of a stimulation signal. When in the second, expanded configuration, the energy delivery assembly 154, and in particular, the individual electrodes 156, is pressed against or otherwise contacts the walls of the patient’s vasculature tissue. Although generally described as transitioning to a spiral and/or helical configuration, it is envisioned that the energy delivery assembly 154 may be deployed in other configurations without departing from the scope of the present disclosure. Further, the mapping catheter 150 may be configurable, for example, using one or more pull wires (not shown) to adjust the configuration to promote contact between the electrodes 156 and the wall of the renal artery. As such, mapping catheter 150 may be capable of being placed in one, two, three, four, or more different configurations depending upon the design needs of the mapping catheter 150 or the location at which therapy is to be applied.
[0048] As depicted in FIG. 7, the elongated shaft 152 may be configured to be received within a portion of a guide catheter or guide sheath (such as a 6F guide catheter) 158 that is utilized to navigate the mapping catheter 150 to a desired location at which point if a guide catheter 158 is retracted to uncover the mapping catheter 150. As noted hereinabove, retraction of the guide catheter 158 may enable the energy delivery assembly 154 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration.
[0049] The elongated shaft 152 of the mapping catheter 150 may further include an aperture (not shown) at a distal end thereof and configured to slidably receive a guidewire over which the mapping catheter 150, either alone or in combination with the guide catheter 158, are advanced. In this manner, the guidewire is utilized to guide the mapping catheter 150 to the target tissue using over-the-wire (OTW) or rapid exchange (RX) techniques, at which point the guide wire may be partially or fully removed from the mapping catheter 150, enabling the mapping catheter 150 to transition from the first, undeployed configuration, to the second, deployed or expanded configuration (FIG. 7). As noted elsewhere herein, the mapping catheter 150 may be transition from the first, undeployed configuration to the second, deployed configuration automatically (e.g., via a shape memory alloy, etc.) or manually (e.g., via pull wires, guide wire manipulation, etc. that is controlled by the clinician).
[0050] Continuing with FIG. 7, in embodiments where the mapping catheter 150 is an RF ablation catheter, the energy delivery assembly 154 includes one or more electrodes 156 disposed on an outer surface thereof that are configured to contact a portion of the patient’s vascular tissue when the mapping catheter 150 is placed in the second, expanded configuration. As shown herein, the mapping catheter 150 includes four electrodes 156. However, the present disclosure is not so limited and the mapping catheter 150 may have more or fewer electrodes 156 without departing from the scope of the present disclosure.
[0051] As illustrated in the figures, the electrodes 156 are disposed in spaced relation to one another along a length of the mapping catheter 150 forming the energy delivery assembly 154. As will be appreciated, these electrodes 156 are in communication with the stimulation source 124.
[0052] The electrodes 156 are in communication with a stimulation source 124 to deliver a stimulation signal to the blood vessel in question. The stimulation signal (e.g., the biphasic waveform), is generated by the stimulation source 124 and communicated to the electrodes 156 causing stimulation of the sympathetic nerves as described herein. In at least one embodiment, during the anodal phase of the biphasic pulse, the stimulation signal is applied to the target tissue via a first of the electrodes 156 and received by a second of the electrodes 156 in a bipolar manner and during the cathodal phase of the biphasic pulse the neurostimulation is applied to the target tissue via the second of the electrodes 156 and received by the first of the electrodes 156 in a bipolar manner. It is envisioned that during the anodal phase or the cathodal phase of the bipolar pulse, the stimulation signal is applied by two or more of the electrodes 156 or received by two or more of the electrodes 156 in any suitable configuration, such as a proximal most electrode 156 and a distal most electrode 156, a proximal most electrode 156 and a next proximal most electrode 56 a proximal most electrode 156 and an electrode 156 disposed just proximal of the distal most electrode 156, etc.
[0053] Further, the stimulation source 124 may employ one or more algorithms 144 for the stimulation of the multiple electrodes 156. For example, if there are four electrodes, the stimulation source 124 may execute an algorithm 144 to achieve a firing order for the electrodes 156 to apply the neurostimulation. In such an example the electrodes 156 may connect in a bipolar fashion as follows. In a first anodal phase between a first electrode and a fourth, first cathodal phase between the fourth electrode and the first electrode. This may be followed by a second cathodal phase between the fourth electrode and the first electrode and a second anodal phase between the first electrode and the fourth electrode. This may be followed in a similar manner by different pairs of electrodes 156, for example between the first and third electrodes 156, the first and second electrodes 156. A similar pattern may be followed between second and fourth electrodes and the second and third electrodes. Still further, an anodal and cathodal phase need not be between the same pairs of electrodes. For example, a first anodal phase may be between a first and a fourth electrode and be followed by a cathodal phase between the fourth and the second electrode. Alternatively, the first anodal phase may be between a first and a fourth electrode and followed by a cathodal phase between the fourth and first electrodes 56, as in the first example, however the second anodal phase may be between the second and the fourth electrodes followed by a second cathodal phase between the fourth and second electrodes. The firing order of the electrodes 156 is limited only by the number of electrodes 156 and the biphasic waveform.
[0054] During the application of the stimulation signal to the target tissue, alternating the leading phase of each successive pulse of the biphasic waveform may stimulate a greater number of nerves within the target tissue as compared to traditional bipolar or monopolar stimulation. By stimulating a greater number of nerves within the target tissue, a desired placement of the electrodes 156 within the target tissue for denervation can be more readily identified to ensure effective renal denervation and an optimal outcome. The location and/or orientation of the electrodes 156 relative to the tissue wall can be altered between the application of stimulation signals to map or otherwise identify optimal nerve candidates for denervation. [0055] As noted above, while aspects of the disclosure are described above in connection with placement of intravascular electrodes 26, for example on a stent 22 or as a screw in electrode 26 (Fig. 4), the disclosure is not so limited. Another option for stimulating nerves to prevent the drop in blood pressure as might be caused by POTS or OH is the use of a spinal cord stimulator assembly. Similar to the aspects described above, a generator 28 can be connected via one or more leads 30 to one or more electrodes 26. The electrodes 26 may be surgically positioned via a lateral placement procedure in one or more positions from the lower thoracic spine (e.g., proximate T12) through the upper lumbar vertebrae. The lead 30 connects the electrodes 26 to the generator 28. Alternatively, the electrodes 26 may be placed in a dorsal root area.
[0056] As with the intravascular aspects of the disclosure described above, application of stimulation via the electrodes 26 at one or more of these locations results in a similar increase in blood pressure in the patient. Any suitable stimulation parameters may be used. In one example, the stimulation is a continuous stimulation having a frequency of 20 Hz and a 600 ps pulse width. In some instances, stimulation results in an increase in blood pressure of about 30 mmHg. The spinal cord stimulator assembly can be initiated following implantation using method 300, described above.
[0057] Although the description of computer-readable media contained herein refers to solid-state storage, it should be appreciated by those skilled in the art that computer-readable storage media can be any available media that can be accessed by the processor 130. That is, computer readable storage media may include non-transitory, volatile, and non-volatile, removable, and non-removable media implemented in any method or technology for storage of information such as computer-readable instructions, data structures, program modules or other data. For example, computer-readable storage media may include RAM, ROM, EPROM, EEPROM, flash memory or other solid-state memory technology, CD-ROM, DVD, Blu-Ray or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which may be used to store the desired information.
[0058] The disclosure of the instant application is further described in the following examples.
[0059] Example 1 : An therapeutic system comprising: an implantable stimulation signal generator; a pair of electrodes in electrical communication with the implantable signal generator, wherein the pair of electrodes are configured for placement proximate sympathetic nerves of a patient; a motion sensor in communication with the implantable stimulation signal generator, wherein upon detection of motion of a patient in excess of a threshold the implantable stimulation signal generator is configured to output a stimulation signal to the electrodes, wherein the stimulation signal is configured to stimulate nerves to cause a blood vessel to contract.
[0060] Example 2: The therapeutic system of example 1, wherein the motion sensor comprises an accelerometer or a gyroscope.
[0061] Example 3: The therapeutic system of any preceding example, wherein the pair of electrodes comprise screw type electrodes configured to screw into a blood vessel wall.
[0062] Example 4: The therapeutic system of any preceding example, further comprising an implantable stent, wherein the pair of electrodes are coupled to the implantable stent.
[0063] Example 5: The therapeutic system of example 4, further comprising a balloon catheter insertable into the blood vessel, wherein expansion of the balloon catheter expands the stent to contact the blood vessel wall.
[0064] Example 6: The therapeutic system of example 1 or 2, wherein the electrodes are configured for placement proximate a spinal nerve. [0065] Example 7: The therapeutic system of example 6, wherein the electrodes are configured for placement proximate spinal nerves located between T12 and the upper lumbar vertebrae.
[0066] Example 8: The therapeutic system of example 1 or 2, wherein the electrodes are configured for placement proximate a dorsal root area of a patient.
[0067] Example 9: The therapeutic system of any preceding example, wherein the signal output to the electrodes comprises a biphasic signal.
[0068] Example 10: The therapeutic system of example 9, wherein the biphasic signal has a frequency of between 10 - 30Hz, a voltage of between approximately 5 - 30 V, a current of between approximately 2 - 500 mA, and a pulse width of between approximately 2 - 10 ms.
[0069] Example 11 : The therapeutic system of any preceding example, wherein the signal output to the electrodes comprises a bipolar signal.
[0070] Example 12: The therapeutic system of example 11, wherein the signal is a continuous stimulation signal having a frequency of 20 Hz and a 600 ps pulse width.
[0071] Example 13: The therapeutic system of any preceding example, wherein the therapeutic system is configured to detect a heart rate sensed via the electrodes.
[0072] Example 14: The therapeutic system of any preceding example, wherein the signal output to the electrodes is triggered by a combination of the detected heart rate and the detected motion in excess of the threshold.
[0073] Example 15: The therapeutic system of any preceding example, further comprising a mapping catheter, wherein the mapping catheter is configured to stimulate nerves proximate a blood vessel for determination of placement of the electrodes.
[0074] While several embodiments of the disclosure have been shown in the drawings, it is not intended that the disclosure be limited thereto, as it is intended that the disclosure be as broad in scope as the art will allow and that the specification be read likewise. Therefore, the above description should not be construed as limiting, but merely as exemplifications of embodiments. Those skilled in the art will envision other modifications within the scope and spirit of the claims appended hereto.
[0075] Further disclosed herein is the subject-matter of the following clauses:
A therapeutic system comprising: an implantable stimulation signal generator; a pair of electrodes in electrical communication with the implantable signal generator, wherein the pair of electrodes are configured for placement proximate sympathetic nerves of a patient; and a motion sensor in communication with the implantable stimulation signal generator, wherein upon detection of motion of a patient in excess of a threshold the implantable stimulation signal generator is configured to output a stimulation signal to the electrodes, wherein the stimulation signal is configured to stimulate nerves to cause a blood vessel to contract. The therapeutic system of clause 1, wherein the motion sensor comprises an accelerometer or a gyroscope. The therapeutic system of clause 1, wherein the pair of electrodes comprise screw type electrodes configured to screw into a blood vessel wall. The therapeutic system of clause 1, further comprising an implantable stent, wherein the pair of electrodes are coupled to the implantable stent. The therapeutic system of clause 4, further comprising a balloon catheter insertable into the blood vessel, wherein expansion of the balloon catheter expands the stent to contact a wall of the blood vessel. The therapeutic system of clause 1, wherein the electrodes are configured for placement proximate a spinal nerve. The therapeutic system of clause 6, wherein the electrodes are configured for placement proximate spinal nerves located between T12 and upper lumbar vertebrae. The therapeutic system of clause 6, wherein the electrodes are configured for placement proximate a dorsal root area of a patient. The therapeutic system of clause 1, wherein contraction of the blood vessel increases a blood pressure of a patient. The therapeutic system of clause 9, wherein the increase in blood pressure counters a drop in blood pressure experienced by a patient due to the detected motion in excess of a threshold. The therapeutic system of clause 10, wherein the drop in blood pressure is related to a patient condition including post tachycardia syndrome and postural orthostatic hypotension. The therapeutic system of clause 1, wherein the signal output to the electrodes comprises a biphasic signal. The therapeutic system of clause 1, wherein the signal output to the electrodes comprises a bipolar signal. The therapeutic system of clause 1, wherein the therapeutic system is configured to detect a heart rate sensed via the electrodes. The therapeutic system of clause 14, wherein the signal output to the electrodes is triggered by a combination of the detected heart rate and the detected motion in excess of the threshold. A method of treating a condition comprising: detecting a motion of a patient; and outputting a stimulation signal from a generator to an electrode located proximate a sympathetic nerve of a patient, wherein the output signal to the electrodes stimulates the sympathetic nerves causing a blood vessel to contract, wherein the contraction of the blood vessel increases a blood pressure of the patient. The method of clause 16 further comprising detecting a heart rate of the patient. The method of clause 17, wherein outputting the stimulation signal is based on the detected motion and the detected heart rate. The method of clause 16, wherein the electrode proximate the sympathetic nerve is placed within a blood vessel of the patient. The method of clause 16, wherein the electrode is proximate spinal nerves located between T12 and upper lumbar vertebrae or proximate a dorsal root area of a patient. A therapeutic system comprising: an implantable stimulation signal generator (28); a pair of electrodes (26) in electrical communication with the implantable signal generator, wherein the pair of electrodes are configured for placement proximate sympathetic nerves of a patient; a motion sensor (46) in communication with the implantable stimulation signal generator, wherein upon detection of motion of a patient in excess of a threshold the implantable stimulation signal generator is configured to output a stimulation signal to the electrodes, wherein the stimulation signal is configured to stimulate nerves to causing a blood vessel to contract. The therapeutic system of claim 20, wherein the motion sensor (46) comprises an accelerometer or a gyroscope. The therapeutic system of claims 20-21, wherein the pair of electrodes (26) comprise screw type electrodes configured to screw into a blood vessel wall. The therapeutic system of claims 20-22, further comprising an implantable stent (22), wherein the pair of electrodes are coupled to the implantable stent. The therapeutic system of claim 23, further comprising a balloon catheter (5) insertable into the blood vessel, wherein expansion of the balloon catheter expands the stent (22) to contact a wall of the blood vessel. The therapeutic system of claim 20 or claim 21, wherein the electrodes (26) are configured for placement proximate spinal nerves. The therapeutic system of claim 25, wherein the electrodes (26) are configured for placement proximate spinal nerves located between T12 and the upper lumbar vertebrae. The therapeutic system of claim 20 or claim 21 , wherein the electrodes (26) are configured for placement proximate a dorsal root area of a patient. The therapeutic system of claims 20-27, wherein the signal output to the electrodes (26) comprises a biphasic signal. The therapeutic system of claim 28, wherein the biphasic signal has a frequency of between 10 - 30Hz, a voltage of between approximately 5 - 30 V, a current of between approximately 2 - 500 mA, and a pulse width of between approximately 2 - 10 ms. The therapeutic system of claims 20-29, wherein the signal output to the electrodes (26) comprises a bipolar signal. The therapeutic system of claim 30, wherein the signal is a continuous stimulation signal having a frequency of 20 Hz and a 600 ps pulse width. The therapeutic system of claims 20-31, wherein the therapeutic system is configured to detect a heart rate sensed via the electrodes (26). The therapeutic system of claims 20-32, wherein the signal output to the electrodes (26) is triggered by a combination of the detected heart rate and the detected motion in excess of the threshold. The therapeutic system of claims 20-33, further comprising a mapping catheter (150), wherein the mapping catheter is configured to stimulate nerves proximate a blood vessel for determination of placement of the electrodes (26).