US 8,876,813 B2Grant

Methods, systems, and apparatus for neural signal detection

Issue Date:2014-11-04

•20 Claims

•8 Drawing Sheets

Abstract

Methods, systems, and apparatus for signal detection are described. In one example, a detection assembly includes a signal detector. The signal detector is configured to receive a sensor signal having a peak magnitude and a first frequency and generate an output signal having a magnitude proportional to the peak magnitude of the sensor signal and having a second frequency less than the first frequency of the sensor signal.

Metadata

Assignee

St. Jude Medical, Inc.

Inventors

Xiaoyi Min
Stuart Rosenberg
Gabriel Mouchawar

Application Information

Application Number:US 13/827,308

Filing Date:2013-03-14

Priority Date:2013-03-14

Art Unit:3739

Classifications

IPC:

A61B18/18A61B5/00A61B18/12A61B5/04A61N1/05

Patent Drawings (8 sheets)

Description

Background of the Disclosure

[0001] a. Field of the Disclosure

[0002] The present disclosure relates generally to methods, systems, and apparatus for signal detection. More particularly, the present disclosure relates neural signal detection methods, systems, and apparatus that utilize a circuit to measure and record the amplitude of nerve firings along the spinal cord and peripheral nerves.

[0003] b. Background Art

[0004] Medical devices and procedures that affect or involve neural signals are known. It is known, for example, that ablation systems are used to perform ablation procedures to treat certain conditions of a patient. A patient experiencing arrhythmia, for example, may benefit from cardiac ablation to prevent irregular heartbeats caused by arrhythmogenic electric signals generated in cardiac tissues. By ablating or altering cardiac tissues that generate such unintended electrical signals, the irregular heartbeats may be stopped. Ablation systems are also known for use in treating hypertension, and in particular drug-resistant hypertension, in patients. In particular, renal ablation systems, also referred to as renal denervation systems, are used to create lesions along the renal sympathetic nerves, which are a network of nerves in the renal arteries that help control and regulate blood pressure. The intentional disruption of the nerve supply has been found to cause blood pressure to decrease. Other medical devices that measure or record neural signals include, spinal cord stimulation (SCS) systems that provide pulsed electrical stimulation to a patient's spinal cord to control chronic pain, and cardiac rhythm management devices (CRMD) used to regulate a patient's heart beat.

[0005] Known techniques for detecting high frequency signals in a body, and particularly high frequency neural signals, typically require very sensitive equipment, as nerve signals differ from cardiac signals and are at a higher frequency and much narrower pulse duration. In particular, neural signals are typically collected through surgically positioned microelectrodes or micropipette electrodes. The signals generated by these sensors are generally sampled by controllers at a sampling rate of about four kilohertz. The sensors and controllers required for such techniques are not inexpensive. Moreover, some medical devices and procedures may benefit from limited information about neural signals and do not require the detailed information that is obtained using the known techniques.

[0006] There is a need, therefore, for neural signal detection systems that do not require expensive, surgically implanted electrodes, utilize simpler and less expensive controllers with relatively low sampling rates, and provide useful data about detected neural signals in real time. It would also be beneficial if the neural signal detection systems were compact in size so that they could be easily built into or onto an ablation catheter, or into or onto an implantable medical device such as a spinal cord stimulator device or a cardiac rhythm management device.

Brief Summary of the Disclosure

[0007] In one aspect, a neural signal detector includes a rectifier circuit and a peak detector circuit operatively connected to the rectifier circuit. The rectifier circuit is configured to receive a time varying neural signal from a neural sensor and output a rectified signal corresponding to the received signal. The rectifier circuit is configured to receive the rectified signal and to provide an output signal proportional to a peak magnitude of the rectified signal.

[0008] In another aspect, a detection assembly includes a signal detector. The signal detector is configured to receive a sensor signal having a peak magnitude and a first frequency and generate an output signal having a magnitude proportional to the peak magnitude of the sensor signal and having a second frequency less than the first frequency of the sensor signal.

[0009] Another aspect of the present disclosure is an ablation system. The ablation system includes a signal detector and a controller. The signal detector is configured to receive, from a neural sensor, a plurality of signals and generate a pre-ablation output signal having a first magnitude proportional to a peak magnitude of at least one pre-ablation signal of the plurality of signals and having a duration greater than said at least one pre-ablation signal of the plurality of signals. The controller is operatively coupled to the signal detector to sample the pre-ablation output signal.

[0010] Another aspect of the present disclosure is an ablation catheter comprising an ablation electrode, a sensing electrode, and a neural signal detector operatively connected to the sensing electrode. The neural signal detector comprises a rectifier circuit configured to receive a time varying neural signal from a neural sensor and output a rectified signal corresponding to the received signal and a peak detector circuit operatively connected to the rectifier circuit to receive the rectified signal and configured to provide an output signal proportional to a peak magnitude of the rectified signal.

[0011] Another aspect of the present disclosure is a spinal cord stimulation device comprising an implantable stimulating electrode, a sensing electrode, and a neural signal detector operatively connected to the sensing electrode. The neural signal detector comprises a rectifier circuit configured to receive a time varying neural signal from a neural sensor and output a rectified signal corresponding to the received signal and a peak detector circuit operatively connected to the rectifier circuit to receive the rectified signal and configured to provide an output signal proportional to a peak magnitude of the rectified signal.

[0012] Another aspect of the present disclosure is a cardiac rhythm management device comprising a pacing lead, a sensing electrode, and a neural signal detector operatively connected to the sensing electrode. The neural signal detector comprises a rectifier circuit configured to receive a time varying neural signal from a neural sensor and output a rectified signal corresponding to the received signal and a peak detector circuit operatively connected to the rectifier circuit to receive the rectified signal and configured to provide an output signal proportional to a peak magnitude of the rectified signal. The foregoing and other aspects, features, details, utilities and advantages of the present disclosure will be apparent from reading the following description and claims, and from reviewing the accompanying drawings.

Brief Description of the Drawings

[0013] FIG. 1 is a block diagram of one embodiment of a signal detection assembly.

[0014] FIG. 2 is a simplified schematic of one example signal detector for use in the detection assembly shown in FIG. 1.

[0015] FIG. 3 is a graphical representation of an example input to the signal detector shown in FIG. 2.

[0016] FIG. 4 is a graphical representation of an example output of the signal detector shown in FIG. 2 in response to the input shown in FIG. 3.

[0017] FIG. 5 is a simplified schematic of another example signal detector for use in the detection assembly shown in FIG. 1.

[0018] FIG. 6 is a graphical representation of an example neural signal that may be detected by the detection assembly shown in FIG. 1.

[0019] FIG. 7 is an isometric view of one embodiment of an ablation system including a generator, a catheter, and a return electrode.

[0020] FIG. 8 is a partial view of a distal end of the catheter shown in FIG. 7.

[0021] FIG. 9 is a plan view of an example neural sensor for use in the system shown in FIG. 7.

[0022] FIG. 10 is a schematic block diagram of a controller for use in the generator shown in FIG. 7.

[0023] Corresponding reference characters indicate corresponding parts throughout the drawings.

Detailed Description of the Disclosure

[0024] The present disclosure is generally directed to methods and systems for measuring and/or recording neural signals along the spinal cord or in peripheral nerves, including cardiac nerves and renal nerves. The methods and systems described herein measure and/or record the amplitude of neural signals. The systems of the present disclosure utilize a small-sized circuit that includes generally a high frequency diode, a capacitor, and a resistor as a demodulator as described herein. In many cases, the circuitry can be sized and configured to fit inside of a medical device or on a lead or catheter. The circuitry for measuring and/or recording the activities of nerves as described herein may be particularly useful for cardiac and renal ablation procedures, as well as for numerous implantable medical devices as described herein.

[0025] This approach may allow an ablation catheter system to measure the success of renal efferent and afferent nerve ablation during a renal denervation procedure to provide immediate success feedback to a doctor throughout an ablation procedure. Further, this approach may allow for spinal cord stimulator devices to provide improved sensing capabilities. Still further, this approach to measuring nerve amplitude may enable responses from interventions between neuro and cardiac rhythm management devices such as the recording of nerve responses from stimulating different sites of T1-T5 and T11-L2 in the spinal cord or sites along the sternum and intracardiac sites. These and other benefits of the disclosure are set forth in detail herein.

[0026] Referring now to the drawings and in particular to FIG. 1, detection assembly 100, includes sensor 102, signal detector 104, and controller 106. Sensor 102 is operable to detect a signal and generate a sensor signal proportional to the detected signal. Sensor 102 is operatively coupled to Signal detector 104. Signal detector 104 receives the sensor signal from sensor 102 and generates an output signal proportional to the sensor signal. Controller 106 is coupled to signal detector 104 to receive the output signal from signal detector 104.

[0027] In the exemplary embodiment, signal detector 104 is configured to generate an output signal having characteristics, such as magnitude, frequency, etc., that controller 106 is operable to sample. In particular, the received signal has a peak magnitude and a first frequency. Signal detector 104 generates an output signal with a magnitude that is proportional to the peak magnitude at a second frequency that is less than the first frequency. In the illustrated embodiment, signal detector 104 generates an output signal with a magnitude that is substantially equal to the peak magnitude of the sensor signal. In other suitable embodiments, signal detector 104 generates an output signal with a magnitude that is greater or lesser than, but proportional to, the peak magnitude of the sensor signal. Thus, controller 106, which may have a sampling resolution too low for accurate sampling of the sensor signal, is provided with the output signal by signal detector 104, at a frequency, the second frequency, that it may accurately sample.

[0028] Referring again to FIG. 1, signal detector 104 includes rectifier circuit 108 and peak detector circuit 110. Rectifier circuit 108 receives the sensor signal, which is a time varying signal and may be an alternating current (AC) signal, at input 112 from sensor 102. Rectifier circuit 108 rectifies the received sensor signal and outputs a rectified signal to peak detector circuit 110. Peak detector circuit 110 detects the peak magnitude of the rectified signal and generates an output signal with a magnitude proportional to the peak magnitude of the rectified signal and the sensor signal at a frequency less than the frequency of the sensor signal. The output signal is output from peak detector circuit 110 and signal detector 104 via output 114. Rectifier circuit 108 and peak detector circuit 110 may include any circuits and/or components suitable for operation as described herein. Some exemplary rectifier circuits suitable for use as rectifier circuit 108 and some exemplary peak detector circuits suitable for use as peak detector circuit 110 are described in detail below.

[0029] The illustrated controller 106 includes processor 116 and memory device 118 coupled to processor 116. Other suitable embodiments do not include processor 116 and/or memory device 118. The term “processor” refers herein generally to any programmable system including systems and microcontrollers, reduced instruction set circuits (RISC), application specific integrated circuits (ASIC), programmable logic circuits, field programmable gate array (FPGA), gate array logic (GAL), programmable array logic (PAL), digital signal processor (DSP), and any other circuit or processor capable of executing the functions described herein. The above examples are exemplary only, and thus are not intended to limit in any way the definition and/or meaning of the term “processor.” Although a single processor is illustrated in FIG. 1, processor 116 may include more than one processor and the actions described herein may be shared by more than one processor. Moreover, although controller 106 is illustrated in FIG. 1 as a component of detection assembly 100, controller 106 may be a part of and/or shared with another system, such as a system with which detection assembly 100 is used.

[0030] Memory device 118 stores program code and instructions, executable by processor 116. When executed by processor 116, the program code and instructions cause processor 116 to operate as described herein. Memory device 118 may include, but is not limited to only include, non-volatile RAM (NVRAM), magnetic RAM (MRAM), ferroelectric RAM (FeRAM), read only memory (ROM), flash memory and/or Electrically Erasable Programmable Read Only Memory (EEPROM). Any other suitable magnetic, optical and/or semiconductor memory, by itself or in combination with other forms of memory, may be included in memory device 118. Memory device 118 may also be, or include, a detachable or removable memory, including, but not limited to, a suitable cartridge, disk, CD ROM, DVD or USB memory. Although illustrated separately from processor 116, memory device 118 may be integrated with processor 116 in other suitable embodiments.

[0031] FIG. 2 is a schematic diagram of an exemplary embodiment of signal detector 104 with a passive rectifier circuit 108 and passive peak detector circuit 110. In the signal detector shown in FIG. 2, input 112 is configured for connection to bipolar sensor 102 (not shown). In other embodiments, input 112 may be configured for connection to any other suitable type of sensor 102 including, for example, a unipolar sensor 102. A feed-through capacitor 200 is coupled to input 112 to pass the sensor signal to passive rectifier circuit 108. In other suitable embodiments, feed-through capacitor 200 is not included in signal detector 104.

[0032] Passive rectifier circuit 108 in FIG. 2 is a positive half-wave rectifier circuit. In other suitable embodiments, passive rectifier circuit 108 may be any other suitable passive rectifier circuit including, for example, a full wave rectifier circuit, a negative half wave rectifier circuit, etc. Passive rectifier circuit 108 includes diode 202. Diode 202 includes anode 204 and cathode 206. Generally, diode 202 conducts current when it is forward biased, i.e., when a bias voltage exceeding a positive threshold voltage differential is applied across diode 202 from anode 204 to cathode 206. Diode 202 blocks current when it is reverse biased, i.e., when a bias voltage that does not exceed the positive threshold voltage differential is applied across diode 202 from anode 204 to cathode 206. In FIG. 2, diode 202 may be a Schottky diode with a relatively low threshold voltage, also referred to as a diode forward voltage drop, between about 0.2 volts and 0.4 volts. In other suitable embodiments, diode 202 is any other suitable type of diode with a relatively low threshold voltage (e.g., less than about 0.5 volts). In some embodiments, diode 202 is a germanium diode. When diode 202 is forward biased, current, e.g., the sensor signal, flows through diode 202 to passive peak detector circuit 110. When diode 202 is reverse biased, e.g., when the voltage differential from anode 204 to cathode 206 is less than the threshold voltage, diode 202 prevents current from flowing between the passive rectifier circuit 108 and passive peak detector circuit 110. Thus, only the positive portion of the rectified signal that exceeds the bias voltage is delivered from passive rectifier circuit 108 to passive peak detector circuit 110.

[0033] Passive peak detector circuit 110 includes resistor 208 and capacitor 210. Resistor 208 is coupled in parallel with capacitor 210. The voltage across capacitor 210 is, via output 114, the output signal of passive peak detector circuit 110 and signal detector 104. When current is permitted to flow through rectifier circuit 108 to peak detector circuit 110, the voltage on capacitor 210 increases as a function of the time constant, tau (τ), defined by the values of paralleled resistor 208 and capacitor 210. More specifically, the time constant is equal to the capacitance of capacitor 210 multiplied by the resistance of resistor 208. Approximately when the rectified signal reaches a peak value and begins to decrease, diode 202 becomes reversed biased, i.e., the difference between the voltage of the sensor signal applied to anode 204 of diode 202 and the voltage across capacitor 210 is less than the threshold voltage of diode 202. Diode 202 no longer conducts current and the voltage on capacitor 210 is discharged through resistor 208 at a rate defined by the time constant. The resistance of resistor 208 and the capacitance of capacitor 210 are selected to result in a time constant large enough that the voltage on the capacitor will discharge slowly enough for controller 106 to accurately sample the peak voltage on capacitor 210. In one example implementation, controller 106 has a sampling resolution of four milliseconds (ms). It is generally desirable for peak detector circuit 110 to have a time constant greater than the sampling resolution of the controller. Accordingly, in this example, resistor 208 has a resistance of about 200 kiloohms (kΩ) and capacitor 210 has a capacitance of about 33 nanofarads (nF), resulting in a time constant of about 6.6 ms. To change the time constant to suit a different sampling rate of controller 106, the resistance of resistor 208 and/or the capacitance of capacitor 210 may be suitably varied.

[0034] A specific example of operation of detection assembly 100 including signal detector 104 as shown in FIG. 2 will be described with reference to FIGS. 3 and 4. For this specific example, a series of pulses of 64 megahertz (MHz) signals were induced on input 112 to simulate a high frequency sensor signal. The 64 MHz signals have a period of about 15.6 nanoseconds (ns). In this example, resistor 208 had a resistance of 30 kΩ and capacitor 210 had a capacitance of 33 picofarads (pF), resulting in a time constant of about one microsecond (μs). FIG. 3 is a graph 300 of the magnitude of induced signals 302 as a function of time. Induced signals 302 had a peak magnitude “P”. Rectifier circuit 108 rectified induced signals 302 and provided the rectified signals (not shown) to peak detector circuit 110. FIG. 4 is a graph 400 of output signal 402 of peak detector circuit 110, i.e., the voltage on capacitor 210. Capacitor 210 charges up to the peak voltage P of induced signals 302. When the induced signal drops below peak magnitude 302, capacitor 210 begins to discharge through resistor 208. Because the time constant of peak detector circuit 110 is relatively large compared to the period of induced signals 302, the voltage on capacitor 210 does not significantly discharge between signals in each pulse of signals in induced signals 302. Following each pulse of signals of induced signals 302, capacitor 210 discharges to approximately zero volts. As a result, output signal 402 is a square wave with a magnitude of approximately peak magnitude P. The period of square wave output signal 402 is significantly longer than the period of induced signals 302. Put another way, the frequency of output signal 402 is significantly less than the frequency of induced signals 302. Thus, controller 106 may accurately sample output signal 402 at a lower frequency and a lower sampling rate than the frequency and sampling rate that would be required to accurately sample induced signals 302.

[0035] Now leaving the specific example, FIG. 5 is a schematic diagram of an exemplary embodiment of signal detector 104 with an active rectifier circuit 108 and passive peak detector circuit 110. A sensor signal is input to signal detector 104 through feed-through capacitor 200 at input 112. Active rectifier circuit 108 receives the sensor signal and outputs a rectified signal to passive peak detector circuit 110. Passive peak detector circuit 110 transmits an output signal through output 114. Passive peak detector circuit includes resistor 208 and capacitor 210. Active rectifier circuit 108 includes full wave rectifier 500 and buffer 502. Buffer 502 is a unity gain buffer amplifier including operational amplifier 504. Buffer 502 has a high impedance input for receiving the output of full wave rectifier 500 and a low impedance output to provide the output signal of full wave rectifier 500 to peak detector circuit 110 with minimal losses. Full wave rectifier 500 includes operational amplifier 506, diode 508, and resistors 510, 512, and 514. When an input signal, such as the sensor signal, is less than zero, full wave rectifier 500 operates as an inverting amplifier with a gain of:

[0036]

\begin{matrix} Inverting gain = - \frac{R 2}{R 1} & (1) \end{matrix}

where R2 is the resistance of resistor 512 and R1 is the resistance of resistor 514. When the input signal is greater than zero, the full wave rectifier has a noninverting gain of:

[0037]

\begin{matrix} Noninverting Gain = \frac{1}{1 + (\frac{R 1 + R 2}{R 3})} & (2) \end{matrix}

where R3 is the resistance of resistor 510. The resistance of resistors 510, 512, and 514 is selected so that the inverting gain and the non-inverting gain are substantially equal to maintain the same proportionality of the output signal for both positive and negative input signals. In one example implementation, resistor 510 has a resistance of 15 kΩ, resistor 512 has a resistance of 5 kΩ, and resistor 514 has a resistance of 10 kΩ. Thus, according to equations (1) and (2), the example active rectifier circuit 108 has an inverting and non-inverting gain of one half Other implementations may be configured to have any other suitable gain, including a gain greater than one. In one example implementation, operational amplifiers 504 and 506 are the two operational amplifiers of a LM358 dual operational amplifier and diode 508 is a 1N4148 diode. In other implementations, any other suitable diode and/or operational amplifiers, including two different operational amplifiers, may be used. It should be understood that active versions of rectifier circuit 108 are not limited to the exemplary rectifier circuit illustrated in FIG. 5 and rectifier circuit 108 may be any suitable active or passive rectifier circuit capable of operating as generally described herein. For example, active rectifier circuit 108 may include a synchronous rectifier, an active half wave rectifier, a dual operation amplifier rectifier, a single operation amplifier (whether full wave or half wave) with or without a buffer, etc.

[0038] The output of active rectifier circuit 108 is provided to passive peak detector circuit 110, which operates as described above. In other embodiments, peak detector circuit 110 is an active peak detector circuit 110 including one or more operation amplifiers. Active peak detector circuits are well known to those of ordinary skill in the art and will not be further described herein.

[0039] Detection assembly 100 may be included in and/or used in conjunction with any system in which relatively high frequency signals are to be sensed. In some exemplary systems, the detection assembly 100 is used to detect neural signals. FIG. 6 shows an example of neural signals 600. In particular, the neural signals 600 are muscle sympathetic nerve activity accessed in the peroneal nerve using microneurography. Each signal has a peak magnitude and a duration. For example, signal 602 has a peak magnitude 604, and a duration 606. The specific magnitude and duration can vary among different nerves, different types of nerves, and among different firings of a single nerve. In general, duration 606 of a nerve signal is relatively short, e.g., one to three milliseconds. As can be seen in FIG. 6, neural signals 600 have varying magnitudes and generally occur stochastically and non-synchronized. Moreover, the rate of nerve firings can vary between five and five thousand firings per second. Because of the high frequency of the nerve signals, accurate detection and reproduction of neural signals, such as neural signals 600, typically requires a relatively high sampling rate, e.g., greater than four kHz. For some uses as described herein, however, reproduction of all of the details of a neural signal is not needed and/or desired. In such instances, detection assembly 100 may be utilized to convert the high frequency, time varying neural signals to lower frequency output signals that indicate the peak magnitude(s) of the neural signals. Thus, controller 106 may utilize a lower sampling rate to gain information about the neural signals than would be required to accurately sample the unmodified neural signals.

[0040] For example, in some embodiments, detection assembly 100 is included in or on, or used in conjunction with, a spinal cord stimulator (SCS). SCS pulse generators apply stimulation to the spinal cord to provide many potential benefits. Detection assembly 100 may be used to sense neural firing patterns along a patient's spinal cord and peripheral nerves for use as feedback for the SCS system, to study the efficacy of treatment, and/or for any other suitable use.

[0041] In other embodiments, the detection assembly is incorporated in or on, or used in conjunction with, a cardiac rhythm medical device (CRMD). Detection assembly 100 may be used to detect cardiac neural signals, which may be used, for example, to determine the response to neuro-stimulations. In still other embodiments, detection assembly 100 may be incorporated within and/or used in conjunction with an ablation system, including both cardiac ablations systems and renal ablation systems. More specifically, in some embodiments, detection system 100 is used to detect neural signals in connection with a neural ablation system. The detection system may be used to detect the magnitude of neural signals before an ablation and after an ablation to facilitate determining the effectiveness of the ablation, and hence the overall procedure. An exemplary ablation system incorporating detection system 100 is described below. It should be understood, however, that the detection system described above may be used with any other suitable system, including SCS systems, other ablation systems, CRMDs, etc. In many embodiments, nerve sensing electrodes including the neural signal detectors described herein may be located close to ablation electrodes or pacing electrodes without interference.

[0042] An exemplary ablation system 700 including detection system 100 will now be described with reference to FIGS. 7-10. Ablation system 700 includes an generator 702, multi-electrode ablation catheter 704, and return electrode 706. Ablation catheter 704 is removably coupled to generator 702 by cable 708. Return electrode 706 is removably coupled to generator 702 by cable 710. In use, return electrode 706 is placed externally against a patient's body and catheter 704 is inserted into the patient's body. Generally, generator 702 outputs radio frequency (RF) energy to catheter 704 through cable 708. The RF energy leaves catheter 704 through a plurality of electrodes 712 (shown in FIG. 8) located at distal end 714 of catheter 704. The RF energy travels through the patient's body to return electrode 706. The dissipation of the RF energy in the body increases the temperature near the electrodes, thereby permitting ablation to occur. In the exemplary embodiment set forth herein, ablation system 700 is a renal ablation system suitable for use in performing renal denervation procedures. It is understood, however, that the ablation system may be used for other treatments, including cardiac ablation treatments, without departing from the scope of the present disclosure.

[0043] Generator 702 includes a user interface (UI) portion 716 for displaying information and notifications to an operator and receiving input from the user. Display devices 718 visually display information, such as measured temperatures, power output of the generator, temperature thresholds, cycle time, etc., and/or notifications to the user. Display devices 718 may include a vacuum fluorescent display (VFD), one or more light-emitting diodes (LEDs), liquid crystal displays (LCDs), cathode ray tubes (CRT), plasma displays, and/or any suitable visual output device capable of displaying graphical data and/or text to a user. Indicators 720 provide visual notifications and alerts to the user. In other embodiments, one or more of indicators 720 provide audible notifications and/or alerts to the user. In the illustrated embodiment, indicators 720 are lights, such as light emitting diodes, incandescent lamps, etc. Indicators 720 may be turned on or off, for example, to indicate whether or not generator 702 is receiving power, whether or not catheter 704 is connected, whether or not catheter 704 (or all electrodes 712) is functioning properly, etc. Moreover, indicators 720 may indicate a quality or degree of a feature or component of ablation system 700, such as by changing color, changing intensity, and/or changing the number of indicators 720 that are turned on. Thus, for example, an indicator 720 may change color to represent a unitless notification of the quality of the contact between one or more of electrodes 712 and an artery wall, or to indicate a comparison between pre-ablation neural signals and post-ablation neural signals. UI portion 716 includes inputs 722, e.g., buttons, keys, knobs, etc., for receiving commands and/or requests from a user.

[0044] As shown in FIG. 8, multiple electrodes 712 may be disposed on basket 724 located at distal end 714 of catheter 704. In the illustrated embodiment, basket 724 is an expandable basket that may be expanded and collapsed by an operator of ablation system 700 to position electrodes 712 against, for example, an artery wall. In the illustrated embodiment, catheter 704 includes four electrodes 712. In other embodiments, catheter 704 may include at least two, but other than four, electrodes 712. A thermocouple (not shown, also referred to herein as a temperature sensor) is attached to each electrode 712 to provide temperature readings of electrode 712. Catheter 704 also contains a thermistor (not shown) and a 1-Wire EEPROM. Generator 702 uses the thermistor for measuring ambient temperature and performing cold-junction compensation on the thermocouples. The EEPROM contains a unique ID which allows generator 702 to reject devices not manufactured specifically for use with generator 702. Generator 702 also maintains usage data on the EEPROM in order to enforce maximum operation limits for catheter 704.

[0045] In the illustrated embodiment shown in FIG. 8, four sensors 102 are disposed on basket 724 near electrodes 712. Sensors 102 may be any sensors suitable for sensing neural firings occurring near sensors 102 and generating a sensor signal representative of the sensed neural firing. In the illustrated embodiment, sensors 102 are non-contact neural sensors; that is, neural sensors that do not require direct contact with a nerve to sense a reading or firing of the nerve. Of course, other sensors that contact the nerve directly are within the scope of the present disclosure. More specifically, as shown in FIG. 9, illustrated sensors 102 are split ring neural sensors. A split ring sensor is a generally toroidal, or ring, shape split into between two and four segments. In the illustrated embodiment shown in FIG. 9, sensor 102 is a four segment split ring. Any two of the segments of the four segment split ring may be utilized as a bipolar sensor. In the exemplary embodiment, signal detector 104 and controller 106 are located within generator 702 (as shown in FIG. 10 and discussed below), and sensor signals are transmitted, such as through a conductor within catheter 704, from sensors 102 to signal detector 104 within generator 702. In other embodiments, signal detector 104 is integrated within catheter 704, and signal detector 104 output signals are transmitted, such as through one or more conductors within catheter 704, from signal detector 104 to controller 106. In still other embodiments, signal detector 104 and controller 106 are incorporated within catheter 704.

[0046] Referring now to FIG. 10, generator 702 includes a power supply 726, a controller 728, and an RF output circuit 730. A multiplexer 740 receives inputs from electrodes 712. Signal detector 104 receives sensor signals from sensors 102 and provides its output signal(s) to controller 728. Power supply 726 receives AC power via an input 732 and converts the received power to a DC power output. The DC power output is provided to the RF output circuit 730 that outputs RF power to catheter 704, and more specifically to electrodes 712, via output 734. Controller 728 is coupled to and controls operation of power supply 726 and RF output circuit 730. Controller 728 controls when and to which electrodes 712 the RF output circuit 730 couples its RF power output. In other embodiments, one or both of the RF output circuit 730 and power supply 726 includes its own controller configured to control operation in response to commands from controller 728. In the illustrated embodiment, controller 728 also functions as controller 106. In other embodiments, controller 106 is separate from controller 728.

[0047] Controller 728 includes processor 736 and memory device 738 coupled to processor 736. The term “processor” refers herein generally to any programmable system including systems and microcontrollers, reduced instruction set circuits (RISC), application specific integrated circuits (ASIC), programmable logic circuits, field programmable gate array (FPGA), gate array logic (GAL), programmable array logic (PAL), digital signal processor (DSP), and any other circuit or processor capable of executing the functions described herein. The above examples are exemplary only, and thus are not intended to limit in any way the definition and/or meaning of the term “processor.” Moreover, although a single processor is illustrated in FIG. 10, processor 736 may include more than one processor and the actions described herein may be shared by more than one processor.

[0048] Memory device 738 stores program code and instructions, executable by processor 736. When executed by processor 736, the program code and instructions cause processor 736 to operate as described herein. Memory device 738 may include, but is not limited to only include, non-volatile RAM (NVRAM), magnetic RAM (MRAM), ferroelectric RAM (FeRAM), read only memory (ROM), flash memory and/or Electrically Erasable Programmable Read Only Memory (EEPROM). Any other suitable magnetic, optical and/or semiconductor memory, by itself or in combination with other forms of memory, may be included in memory device 738. Memory device 738 may also be, or include, a detachable or removable memory, including, but not limited to, a suitable cartridge, disk, CD ROM, DVD or USB memory. Although illustrated separately from processor 736, memory device 738 may be integrated with processor 736.

[0049] In operation, when catheter 704 is positioned at a location for an ablation, each sensor 102 detects neural signals having neural activity near itself. These pre-ablation neural signals are transmitted to signal detector 104, which generates pre-ablation output signals having magnitudes proportional to the peak magnitudes of detected neural signals and a frequency less than the frequency of the original neural signals. After an ablation has occurred at a location, post-ablation neural signals are sensed and transmitted from sensors 102 to signal detector 104. Signal detector 104 generates post-ablation output signals having magnitudes proportional to the peak magnitudes of detected post-ablation neural signals and a frequency less than the frequency of the post-ablation neural signals. Controller 728 samples the pre-ablation and post-ablation output signals at a sampling frequency that is less than the twice the frequency of the pre-ablation and post-ablation neural signals. In other embodiments, controller 728 samples the pre-ablation and post-ablation output signals at a sampling frequency that is less than the frequency of the pre-ablation and post-ablation neural signals. In some embodiments, the controller samples the pre-ablation and post-ablation output signals at a sampling frequency of about 512 Hz. In other embodiments, the controller samples the pre-ablation and post-ablation output signals at a sampling frequency of about 200 Hz. In some embodiments, the controller samples the pre-ablation and post-ablation output signals at a sampling frequency selected as a function of the time constant of signal detector 104. After sampling the pre-ablation and/or post-ablation output signals, controller 728 may store the sampled signals, such as in memory device 738.

[0050] Controller 728 determines a difference between the magnitudes of the pre-ablation output signals and the post-ablation output signals and generates an indication of the determined difference. The indication may be a visual or audible indication. For example, controller 728 may display a value of the difference, e.g., an average percentage difference, on display device 718, may display an indication of the difference using indicators 720, may audibly announce an indication of the difference, etc. In some embodiments, controller 728 compares the determined difference to a predetermined threshold value and generates an indication of whether or not the difference exceeds the threshold value. Thus, for example, if a 75% decrease in the magnitude of the neural signals is desired for an ablation to be considered successful, controller 728 may determine whether or not the post-ablation output signals indicate a 75% decrease from the pre-ablation output signals. If controller 728 determines that the threshold has been exceeded, controller 728 may provide an indication, whether audible or visual, that the ablation was successful. In other embodiments, controller 728 provides an indication when the ablation is unsuccessful.

[0051] Although certain embodiments of this disclosure have been described above with a certain degree of particularity, those skilled in the art could make numerous alterations to the disclosed embodiments without departing from the spirit or scope of this disclosure. All directional references (e.g., upper, lower, upward, downward, left, right, leftward, rightward, top, bottom, above, below, vertical, horizontal, clockwise, and counterclockwise) are only used for identification purposes to aid the reader's understanding of the present disclosure, and do not create limitations, particularly as to the position, orientation, or use of the disclosure. Joinder references (e.g., attached, coupled, connected, and the like) are to be construed broadly and may include intermediate members between a connection of elements and relative movement between elements. As such, joinder references do not necessarily infer that two elements are directly connected and in fixed relation to each other. It is intended that all matter contained in the above description or shown in the accompanying drawings shall be interpreted as illustrative only and not limiting. Changes in detail or structure may be made without departing from the spirit of the disclosure as defined in the appended claims.

[0052] When introducing elements of the present disclosure or the various versions, embodiment(s) or aspects thereof, the articles “a”, “an”, “the” and “said” are intended to mean that there are one or more of the elements. The terms “comprising”, “including” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements. The use of terms indicating a particular orientation (e.g., “top”, “bottom”, “side”, etc.) is for convenience of description and does not require any particular orientation of the item described.

[0053] As various changes could be made in the above without departing from the scope of the disclosure, it is intended that all matter contained in the above description and shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

Claims

What is claimed is:

1. A system for signal detection comprising:

a signal detector configured to:

receive, from a neural sensor, a plurality of signals; and

generate a pre-ablation output signal having a first magnitude proportional to a peak magnitude of at least one pre-ablation signal of the plurality of signals and having a duration greater than said at least one pre-ablation signal of the plurality of signals; and

a controller operatively coupled to the signal detector to sample the pre-ablation output signal.

2. The system of claim 1 wherein the signal detector is configured to generate a post-ablation output signal having a second magnitude proportional to a peak magnitude of at least one post-ablation signal of the plurality of signals and having a duration greater than said at least one post-ablation signal, and wherein the controller is configured to sample the post-ablation output signal.

3. The system of claim 2 wherein the controller is further configured to determine a difference between the pre-ablation output signal and the post ablation output signal.

4. The system of claim 3 wherein the controller is further configured to generate an indication of the determined difference between the pre-ablation output signal and the post ablation output signal.

5. The system of claim 1 wherein the signal detector comprises a rectifier circuit and a peak detector circuit.

6. The system of claim 5 wherein the rectifier circuit is configured to receive the plurality of signals and output a rectified signal corresponding to the peak magnitude of the at least one pre-ablation signal.

7. The system of claim 6 wherein the peak detector circuit is operatively connected to the rectifier circuit to receive the rectified signal and configured to provide the pre-ablation output signal having the first magnitude and the duration greater than said at least one pre-ablation signal.

8. The system of claim 5 wherein the rectifier circuit comprises a passive rectifier circuit.

9. The system of claim 8 wherein the passive rectifier circuit includes a diode.

10. The system of claim 9 wherein the diode is a Schottky diode.

11. The system of claim 5 wherein the rectifier circuit comprises an active rectifier circuit.

12. The system of claim 11 wherein the active rectifier circuit comprises a full wave active rectifier.

13. The system of claim 5 wherein the peak detector circuit comprises a passive peak detector circuit.

14. The system of claim 13 wherein the passive peak detector circuit comprises a resistor coupled in parallel with a capacitor.

15. The system of claim 5 wherein the peak detector circuit is an active peak detector circuit.

16. The system of claim 15 wherein the active peak detector circuit comprises at least one operational amplifier.

17. The system of claim 1 further comprising a neural sensor operatively coupled to the signal detector and operable to generate the plurality of signals.

18. The system of claim 17 wherein the neural sensor is operable to generate the plurality of signals in response to neural signals proximate the neural sensor.

19. The system of claim 1 wherein the controller is operable to sample the pre-ablation output signal at a maximum sampling rate less than a frequency of the plurality of signals.

20. The system of claim 1 wherein the controller is operable to sample the pre-ablation output signal at a maximum sampling rate less than twice a frequency of the plurality of signals.

Patent Citations (124)

Patent	Date	Inventor	Cited By
US3650277(A)	1972-03-01	Sjostrand et al.	Applicant
US4658819(A)	1987-04-01	Harris et al.	Applicant
US5035694(A)	1991-07-01	Kasprzyk et al.	Applicant
US5255679(A)	1993-10-01	Imran	Applicant
US5300068(A)	1994-04-01	Rosar et al.	Applicant
US5368591(A)	1994-11-01	Lennox et al.	Applicant
US5387233(A)	1995-02-01	Alferness et al.	Applicant
US5465717(A)	1995-11-01	Imran et al.	Applicant
US5531779(A)	1996-07-01	Dahl et al.	Applicant
US5598848(A)	1997-02-01	Swanson et al.	Applicant
US5607462(A)	1997-03-01	Imran	Applicant
US5628313(A)	1997-05-01	Webster, Jr.	Applicant
US5676662(A)	1997-10-01	Fleischhacker et al.	Applicant
US5707400(A)	1998-01-01	Terry, Jr. et al.	Applicant
US5769077(A)	1998-06-01	Lindegren	Applicant
US5772590(A)	1998-06-01	Webster, Jr.	Applicant
US5893885(A)	1999-04-01	Webster, Jr.	Applicant
US5897553(A)	1999-04-01	Mulier et al.	Applicant
US5954649(A)	1999-09-01	Chia et al.	Applicant
US5954719(A)	1999-09-01	Chen et al.	Applicant
US6004269(A)	1999-12-01	Crowley et al.	Applicant
US6012457(A)	2000-01-01	Lesh	Applicant
US6016437(A)	2000-01-01	Tu et al.	Applicant
US6024740(A)	2000-02-01	Lesh et al.	Applicant
US6073048(A)	2000-06-01	Kieval et al.	Applicant
US6096037(A)	2000-08-01	Mulier et al.	Applicant
US6117101(A)	2000-09-01	Diederich et al.	Applicant
US6161543(A)	2000-12-01	Cox et al.	Applicant
US6178349(B1)	2001-01-01	Kieval	Applicant
US6200312(B1)	2001-03-01	Zikorus et al.	Applicant
US6216044(B1)	2001-04-01	Kordis	Applicant
US6233491(B1)	2001-05-01	Kordis et al.	Applicant
US6283951(B1)	2001-09-01	Flaherty et al.	Applicant
US6287608(B1)	2001-09-01	Levin et al.	Applicant
US6292695(B1)	2001-09-01	Webster, Jr. et al.	Applicant
US6322559(B1)	2001-11-01	Daulton et al.	Applicant
US6460545(B2)	2002-10-01	Kordis	Applicant
US6522926(B1)	2003-02-01	Kieval et al.	Applicant
US6613045(B1)	2003-09-01	Laufer et al.	Applicant
US6616624(B1)	2003-09-01	Kieval	Applicant
US6635054(B2)	2003-10-01	Fjield et al.	Applicant
US6656174(B1)	2003-12-01	Hegde et al.	Applicant
US6669655(B1)	2003-12-01	Acker et al.	Applicant
US6699231(B1)	2004-03-01	Sterman et al.	Applicant
US6748255(B2)	2004-06-01	Fuimaono et al.	Applicant
US6805131(B2)	2004-10-01	Kordis	Applicant
US6845267(B2)	2005-01-01	Harrison et al.	Applicant
US6954977(B2)	2005-10-01	Maguire et al.	Applicant
US6970730(B2)	2005-11-01	Fuimaono et al.	Applicant
US7122031(B2)	2006-10-01	Edwards et al.	Applicant
US7149574(B2)	2006-12-01	Yun et al.	Applicant
US7155284(B1)	2006-12-01	Whitehurst et al.	Applicant
US7162303(B2)	2007-01-01	Levin et al.	Applicant
US7245955(B2)	2007-07-01	Rashidi	Applicant
US7291146(B2)	2007-11-01	Steinke et al.	Applicant
US7363076(B2)	2008-04-01	Yun et al.	Applicant
US7419486(B2)	2008-09-01	Kampa	Applicant
US7465288(B2)	2008-12-01	Dudney et al.	Applicant
US7468062(B2)	2008-12-01	Oral et al.	Applicant
US7481803(B2)	2009-01-01	Kesten et al.	Applicant
US7653438(B2)	2010-01-01	Deem et al.	Applicant
US7717948(B2)	2010-05-01	Demarais et al.	Applicant
US7742795(B2)	2010-06-01	Stone et al.	Applicant
US7850685(B2)	2010-12-01	Kunis et al.	Applicant
US7949407(B2)	2011-05-01	Kaplan et al.	Applicant
US8145316(B2)	2012-03-01	Deem et al.	Applicant
US8224416(B2)	2012-07-01	de la Rama et al.	Applicant
US8343213(B2)	2013-01-01	Salahieh et al.	Applicant
US8347891(B2)	2013-01-01	Demarais et al.	Applicant
US8419728(B2)	2013-04-01	Klotz et al.	Examiner
US8442639(B2)	2013-05-01	Walker et al.	Applicant
US8454594(B2)	2013-06-01	Demarais et al.	Applicant
US8545495(B2)	2013-10-01	Scheib	Applicant
US2002/0068885(A1)	2002-06-01	Harhen et al.	Applicant
US2002/0120304(A1)	2002-08-01	Mest	Applicant
US2003/0050681(A1)	2003-03-01	Pianca et al.	Applicant
US2003/0060858(A1)	2003-03-01	Kieval et al.	Applicant
US2003/0074039(A1)	2003-04-01	Puskas	Applicant
US2003/0114739(A1)	2003-06-01	Fuimaono et al.	Applicant
US2003/0216792(A1)	2003-11-01	Levin et al.	Applicant
US2003/0233099(A1)	2003-12-01	Danaek et al.	Applicant
US2004/0215186(A1)	2004-10-01	Cornelius et al.	Applicant
US2005/0090756(A1)	2005-04-01	Wolf et al.	Examiner
US2005/0113744(A1)	2005-05-01	Donoghue et al.	Examiner
US2005/0149133(A1)	2005-07-01	Libbus et al.	Examiner
US2005/0288730(A1)	2005-12-01	Deem et al.	Applicant
US2006/0089678(A1)	2006-04-01	Shalev	Applicant
US2007/0135875(A1)	2007-06-01	Demarais et al.	Applicant
US2008/0255478(A1)	2008-10-01	Burdette	Applicant
US2009/0076409(A1)	2009-03-01	Wu et al.	Applicant
US2010/0016762(A1)	2010-01-01	Thapliyal et al.	Applicant
US2010/0094209(A1)	2010-04-01	Drasler et al.	Applicant
US2010/0168737(A1)	2010-07-01	Grunewald	Applicant
US2010/0249773(A1)	2010-09-01	Clark et al.	Applicant
US2010/0268307(A1)	2010-10-01	Demarais et al.	Applicant
US2010/0286684(A1)	2010-11-01	Hata et al.	Applicant
US2011/0004087(A1)	2011-01-01	Fish et al.	Applicant
US2011/0118726(A1)	2011-05-01	de la Rama et al.	Applicant
US2011/0137298(A1)	2011-06-01	Nguyen et al.	Applicant
US2011/0160720(A1)	2011-06-01	Johnson	Applicant
US2011/0213231(A1)	2011-09-01	Hall et al.	Applicant
US2011/0257641(A1)	2011-10-01	Hastings et al.	Applicant
US2011/0264011(A1)	2011-10-01	Wu et al.	Applicant
US2011/0264086(A1)	2011-10-01	Ingle	Applicant
US2012/0143097(A1)	2012-06-01	Pike, Jr.	Applicant
US2012/0143298(A1)	2012-06-01	Just et al.	Applicant
US2012/0296232(A1)	2012-11-01	Ng	Applicant
US2012/0323233(A1)	2012-12-01	Maguire et al.	Applicant
US2013/0116737(A1)	2013-05-01	Edwards et al.	Applicant
US2013/0131743(A1)	2013-05-01	Yamasaki et al.	Applicant
US2013/0144251(A1)	2013-06-01	Sobotka	Applicant
US2013/0172715(A1)	2013-07-01	Just et al.	Applicant
WO97/45157	1997-12-01		Applicant
WO/66020	2000-11-01		Applicant
WO1/00273	2001-01-01		Applicant
WO1/22897	2001-04-01		Applicant
WO2/26314	2002-04-01		Applicant
WO3/082080	2003-10-01		Applicant
WO2006/041881	2006-04-01		Applicant
WO2007/149970	2007-12-01		Applicant
WO2008/141150	2008-11-01		Applicant
WO2008/151001	2008-12-01		Applicant
WO2012/064818	2012-05-01		Applicant
WO2012/106492	2012-08-01		Applicant

Non-Patent Literature (251)

Abboud, Francois M., The Sympathetic System in Hypertension, State-of-the-Art Review, Hypertension Journal of the American Heart Association, Hypertension 4 (suppl II): II-208-II-225, 1982.Applicant
Allen, Edgar V., Sympathectomy for Essential Hypertension, Circulation Journal of the American Heart Association, vol. VI, Jul. 1952, 131-140.Applicant
Anderson, Erling A. et al, Elevated Sympathetic Nerve Activity in Borderline Hypertensive Humans, Evidence From Direct Intraneural Recordings, Hypertension Journal of the American Heart Association, vol. 14, No. 2, Aug. 1989, 177-183.Applicant
Arentz, Thomas et al, Feasibility and Safety of Pulmonary Vein Isolation Using a New Mapping and Navigation System in Patients with Refractory Atrial Fibrillation, Circulation Journal of the American Heart Association, Nov. 18, 2003, 2484-2490.Applicant
Badoer, Emilio et al, Cardiac Afferents Play the Dominant Role in Renal Nerve Inhibition Elicited by Volume Expansion in the Rabbit, American Journal of Physiology, 1998, R383-R388.Applicant
Bao, Gang et al, Blood Pressure Response to Chronic Episodic Hypoxia: Role of the Sympathetic Nervous System, American Journal of Physiology, 1997, 95-101.Applicant
Barajas, Luciano et al, Anatomy of the Renal Innervation: Intrarenal Aspects and Ganglia of Origin, Canadian Journal of Physiology and Pharmacology, vol. 70, No. 5, May 1992, 735-749.Applicant
Barajas, Luciano et al, Monoaminergic Innervation of the Rat Kidney: A Quantitative Study, American Journal of Physiology, vol. 259, No. 3, Sep. 1990, F503-F511.Applicant
Bardram, Linda et al, Late Results After Surgical Treatment of Renovascular Hypertension, A Follow-up Study of 122 Patients 2-18 Years After Surgery, Annals of Surgery, vol. 201, No. 2, Feb. 1985, 219-224.Applicant
Bello-Reuss, Elsa et al, Effect of Renal Sympathetic Nerve Stimulation on Proximal Water and Sodium Reabsorption, The Journal of Clinical Investigation, vol. 57, Apr. 1976, 1104-1107.Applicant
Bello-Reuss, Elsa et al, Effects of Acute Unilateral Renal Denervation in the Rat, The Journal of Clinical Investigation, vol. 56, Jul. 1975, 208-217.Applicant
Benito, Fernando et al, Radiofrequency Catheter Ablation of Accessory Pathways in Infants, Heart, 1997, 78, 160-162.Applicant
Bertog, Stefan C. et al, Renal Denervation for Hypertension, JACC: Cardiovascular Interventions, vol. 5, No. 3, Mar. 2012, 249-258.Applicant
Bertram, Harald et al, Coronary Artery Stenosis After Radiofrequency Catheter Ablation of Accessory Atrioventricular Pathways in Children with Ebstein's Malformation, Circulation Journal of the American Heart Association, 2001, 538-543.Applicant
Blankestijn, Peter J. et al, Sympathetic Overactivity in Renal Failure Controlled by ACE Inhibition: Clinical Significance, Nephrol Dial Transplant, 2000, 15, 755-758.Applicant
Blum, Ulrich et al, Treatment of Ostial Renal-Artery Stenoses with Vascular Endoprostheses After Unsuccessful Balloon Angioplasty, The New England Journal of Medicine, vol. 336, No. 7, Feb. 1997, 459-465.Applicant
Brookes, Linda et al, Renal Denervation: Is Reality Meeting Expectations?, An Interview with Michel Azizi, MD, PhD, Medscape, Jan. 7, 2013.Applicant
Bunte, Matthew C. et al, Endovascular Treatment of Resistant and Uncontrolled Hypertension, JACC: Cardiovascular Interventions, vol. 6, No. 1, 2013, 1-9.Applicant
Callens, David J. et al, Narrowing of the Superior Vena Cava-Right Atrium Junction During Radiofrequency Catheter Ablation for Inappropriate Sinus Tachycardia: Analysis with Intracardiac Echocardiography, Journal of the American College of Cardiology, vol. 33, No. 6, 1999, 1667-1670.Applicant
Campese, Vito M. et al, Renal Afferent Denervation Prevents Hypertension in Rats With Chronic Renal Failure, Hypertension, 1995, 25, 878-882.Applicant
Campese, V.M., Is Hypertension in Chronic Renal Failure Neurogenic in Nature?, Nephrol Dial Transplant, 1994, 9: 741-742.Applicant
Campese, Vito M. et al, Neurogenic Factors in Renal Hypertension, Current Hypertension Reports, 2002 4: 256-260.Applicant
Campese, Vito M. et al, Renal Afferent Denervation Prevents the Progression of Renal Disease in the Renal Ablation Model of Chronic Renal Failure in Rat, American Journal of Kidney Disease, vol. 26, No. 5, Nov. 1995, 861-865.Applicant
Chabanier, H. et al, On the Decapsulation and Neurectomy of the Kidnesy in Permanent Hypertensive States, The Medical Press, Feb. 22, 1936, No. 16, 307-310.Applicant
Ciccone, C D et al, Effects of Acute Renal Denervation on Kidney Function in Deoxycorticosterone Acetate-Hypertensive Swine, Hypertension Journal of the American Heart Association, Oct. 1986, vol. 8, No. 10, 925-931.Applicant
Ciriello, John et al, Renal Afferents and Hypertension, Current Hypertension Reports 2002, 4:136-142.Applicant
Converse, Richard L. et al, Sympathetic Overactivity in Patients with Chronic Renal Failure, The New England Journal of Medicine, vol. 327, No. 27, 1992, 1912-1918.Applicant
Cruickshank, J.M., Beta-Blockers Continue to Surprise Us, European Heart Journal (2000) 21, 354-364.Applicant
Curtis, John J. et al, Surgical Therapy for Persistent Hypertension After Renal Transplantation, Transplantation, vol. 31, No. 2, 1981, 125-128.Applicant
Dequattro V. et al, The Sympathetic Nervous System: The Muse of Primary Hypertension, Journal of Human Hypertension, 2002, 16 (Suppl 1), S64-S69.Applicant
Dibona, Gerald F., Neural Control of the Kidney: Functionally Specific Renal Sympathetic Nerve Fibers, American Journal of Physiology, 2000, 279, R1517-R1524.Applicant
Dibona, Gerald F. et al, Translational Medicine: The Antihypertensive Effect of Renal Denervation, Americal Journal of Physiology, 2010, 298, R245-R253.Applicant
Dibona, Gerald F. et al, Neural Control of Renal Function, Physiological Reviews, vol. 77, No. 1, Jan. 1997, 75-197.Applicant
Dibona, Gerald F., Renal Innervation and Denervation: Lessons from Renal Transplantation Reconsidered, Artificial Organs, vol. 11, No. 6, 1987, 457-462.Applicant
Dibona, Gerald F., Neural Control of Renal Function: Cardiovascular Implications, Hypertension Journal of The American Heart Association, vol. 13, No. 6, Part 1, Jun. 1989, 539-548.Applicant
Dibona, Gerald F., Neural Control of the Kidney: Past, Present, and Future, Hypertension Journal of The American Heart Association, vol. 41, Mar. 2003, Part II, 621-624.Applicant
Dibona, Gerald F., The Sympathetic Nervous System and Hypertension, Hypertension Journal of The American Heart Association, Vo. 43, Feb. 2004, 147-150.Applicant
Dubuc, Marc et al, Feasibility of Cardiac Cryoablation Using a Transvenous Steerable Electrode Catheter, Journal of Interventional Cardiac Electrophysiology, 1998, 2: 285-292.Applicant
Esler, M. et al, Sympathetic Nerve Activity and Neurotransmitter Release in Humans: Translation from Pathophysiology into Clinical Practice, Scandinavian Physiological Society, 2003, 177, 275-284.Applicant
Esler, Murray et al, Assessment of Human Sympathetic Nervous System Activity from Measurements of Norepinephrine Turnover, Hypertension Journal of The American Heart Association, vol. 11, No. 1, Jan. 1988, 3-20.Applicant
Evelyn, Kenneth A. et al, Effect of Thoracolumbar Sympathectomy on the Clinical Course of Primary (Essential) Hypertension, American Journal of Medicine, Feb. 1960, 188-221.Applicant
Freyberg, R. H. et al, The Effect on the Kidney of Bilateral Splanchnicectomy in Patients with Hypertension, The Journal of Clinical Investigation, vol. 16, Issue 1, Jan. 1937, 49-65.Applicant
Gazdar, A. F. et al, Neural Degeneration and Regeneration in Human Renal Transplants, The New England Journal of Medicine, vol. 238, No. 5, Jul. 1970, 222-224.Applicant
Golwyn, Daniel H. et al, Percutaneous Transcatheter Renal Ablation with Absolute Ethanol for Uncontrolled Hypertension or Nephrotic Syndrome: Results in 11 Patients with End-Stage Renal Disease, Journal of Vascular and Interventional Radiology, Jul.-Aug. 1997, vol. 8, No. 4, 527-533.Applicant
Gorisch, Wolfram et al, Heat-Induced Contraction of Blood Vessels, Lasers in Surgery and Medicine 2:I-13 (1982).Applicant
Grassi, Guido et al, Baroreflex Control of Sympathetic Nerve Activity in Essential and Secondary Hypertension, Hypertension Journal of the American Heart Association, 1998;31:68-72.Applicant
Grimson, Keith S. et al, Results of Treatment of Patients with Hypertension by Total Thoracic and Partial to Total Lumbar Sympathectomy, Splanchnicectomy and Celiac Ganglionectomy, Annals of Surgery, Jun. 1949, vol. 129, No. 6, 850-871.Applicant
Grimson, Keith S. et al, Total Thoracic and Partial to Total Lumbar Sympathectomy, Splanchnicectomy and Celiac Ganglionectomy for Hypertension, Annals of Surgery, Oct. 1953, vol. 138, No. 4, 532-547.Applicant
Grimson, Keith S., Total Thoracic and Partial to Total Lumbar Sympathectomy and Celiac Ganglionectomy in the Treatment of Hypertension, Annals of Surgery, Oct. 1941, vol. 114, No. 4, 753-775.Applicant
Guyton, Arthur C., Blood Pressure Control Special Role of the Kidneys and Body Fluids, Science, vol. 252, Jun. 1991, 1813-1816.Applicant
Morrissey, D.M. et al, Sympathectomy in the Treatment of Hypertension, The Lancet, Feb. 1953, 403-408.Applicant
Mortara, Andrea et al, Nonselective Beta-Adrenergic Blocking Agent, Carvedilol, Improves Arterial Baroflex Gain and Heart Rate Variability in Patients With Stable Chronic Heart Failure, Journal of the American College of Cardiology, vol. 36, No. 5, 2000, 1612-1618.Applicant
Naghavi, Morteza et al, Thermography Basket Catheter: In Vivo Measurement of the Temperature of Atherosclerotic Plaques for Detection of Vulnerable Plaques, Catheterization and Cardiovascular Interventions 59:52-59 (2003).Applicant
Naidoo, N. et al, Thoracic Splanchnic Nerves: Implications for Splanchnic Denervation, Journal of Anatomy, Nov. 2001;199(Pt 5):585-590.Applicant
Nakagawa, Hiroshi et al, Inverse Relationship Between Electrode Size and Lesion Size During Radiofrequency Ablation With Active Electrode Cooling, Circulation. Aug. 4, 1998;98(5):458-465.Applicant
Nakagawa, A. et al, Selective Ablation of Porcine and Rabbit Liver Tissue Using Radiofrequency: Preclinical Study, European Surgical Research, 1999;31:371-379.Applicant
Nanni, Gregg S. et al, Control of Hypertension by Ethanol Renal Ablation, Radiology 148: 51-54, Jul. 1983.Applicant
Ndegwa, S., Catheter-Based Renal Denervation for Treatment-Resistant Hypertension [Issues in emerging health technologies issue 121]. Ottawa: Canadian Agency for Drugs and Technologies in Health; 2013.Applicant
Neutel, Joel M., Hypertension and Its Management: A Problem in Need of New Treatment Strategies, Journal of Renin-Angiotensin-Aldosterone System 2000 1: S10-S13.Applicant
Newcombe, C.P. et al, Sympathectomy for Hypertension, British Medical Journal, Jan. 1959, 142-144.Applicant
Ng, Fu Siong et al, Catheter Ablation of Atrial Fibrillation, Clinical Cardiology, 25, 384-394 (2002).Applicant
Norman, Roger A. et al, Role of the Renal Nerves in One-Kidney, One Clip Hypertension in Rats, Hypertension Journal of The American Heart Association, 1984;6:622-626.Applicant
Nozawa, Takashi et al, Effects of Long-Term Renal Sympathetic Denervation on Heart Failure After Myocardial Infarction in Rats, Heart Vessels (2002) 16:51-56.Applicant
O'Connor, Brian K. et al, Radiofrequency Ablation of a Posteroseptal Accessory Pathway Via the Middle Cardiac Vein in a Six-Year-Old Child, PACE, vol. 20, Oct. 1997, Part 1, 2504-2507.Applicant
O'Hagen, Kathleen P. et al, Renal Denervation Decreases Blood Pressure in DOCA-Treated Miniature Swine With Established Hypertension, American Journal of Hypertension, 1990; 3:62-64.Applicant
Oliveira, Vera L.L. et al, Renal Denervation Normalizes Pressure and Baroreceptor Reflex in High Renin Hypertension in Conscious Rats, Hypertension vol. 19, No. 2 Feb. 1992, Supplement II, II-17-II-21.Applicant
Omran, Heyder et al, Echocardiographic Imaging of Coronary Sinus Diverticula and Middle Cardiac Veins in Patients with Preexcitation Syndrome: Impact—on Radiofrequency Catheter Ablation of Posteroseptal Accessory Pathways, PACE, vol. 18, Jun. 1995, 1236-1243.Applicant
Oral, Hakan et al, Pulmonary Vein Isolation for Paroxysmal and Persistent Atrial Fibrillation, Circulation Journal of The American Heart Association, 2002;105:1077-1081.Applicant
Osborn, Jeffrey L. et al, Long-Term Increases in Renal Sympathetic Nerve Activity and Hypertension, Clinical and Experimental Pharmacology and Physiology (1997) 24,72-76.Applicant
Osborn, John W., The Sympathetic Nervous System and Long-Term Regulation of Arterial Pressure: What Are the Critical Questions?, Clinical and Experimental Pharmacology and Physiology (1997) 24, 68-71.Applicant
Ou, Baiqing et al, Baroreflex Sensitivity Predicts the Induction of Ventricular Arrhythmias by Cesium Chloride in Rabbits, Japanese Circulation Journal, 1999; 63: 783-788.Applicant
Page, Irvine H. et al, Mechanisms, Diagnosis and Treatment of Hypertension of Renal Vascular Origin, Annal of Internal Medicine, Aug. 1959, vol. 51, No. 2, 196-211.Applicant
Page, Max, Section of Surgery, Discussion on the Surgical Treatment of Hypertension, Proceedings of the Royal Society of Medicine, vol. XLI, Feb. 1948, 359-372.Applicant
Page, Irvine H. et al, The Effect of Renal Denervation on the Level of Arterial Blood Pressure and Renal Function in Essential Hypertension, Journal of Clinical Investigation, 1935;14(1):27-30.Applicant
Page, Irvine H., The Effect of Renal Efficiency of Lowering Arterial Blood Pressure in Cases of Essential Hypertension and Nephritis, Journal of Clinical Investigation, Nov. 1934; 13(6): 909-915.Applicant
Papademetriou, Vasilios, Hypertension and the Simplicity Renal Denervation System, Scientific Background, www.medtronic.com, 2011.Applicant
Pappone, Carlo et al, Circumferential Radiofrequency Ablation of Pulmonary Vein Ostia: A New Anatomic Approach for Curing Atrial Fibrillation, Circulation, Journal of The American Heart Association, 2000;102:2619-2628.Applicant
Parati, Gianfranco et al, The Human Sympathetic Nervous System: Its Relevance in Hypertension and Heart Failure, European Heart Journal (2012) 33, 1058-1066.Applicant
Pearce, John A. et al, Blood Vessel Architectural Features and Their Effect on Thermal Phenomena, Critical Reviews, vol. CR75, 231-277.Applicant
Peet, Max Minor, Hypertension and Its Surgical Treatment by Bilateral Supradiaphragmatic Splanchnicectomy, American Journal of Surgery, vol. 75, Issue 1, Jan. 1948, 48-68.Applicant
Peterson, Helen Hogh et al, Lesion Dimensions During Temperature-Controlled Radiofrequency Catheter Ablation of Left Ventricular Porcine Myocardium Impact of Ablation Site, Electrode Size, and Convective Cooling, Circulation Journal of The American Heart Association, 1999;99:319-325.Applicant
Plouin, Pierre-Francois et al, Blood Pressure Outcome of Angioplasty in Atherosclerotic Renal Artery Stenosis A Randomized Trial, Hypertension Journal of the American Heart Association, 1998;31:823-829.Applicant
Poutasse, Eugene F., Surgical Treatment of Renal Hypertension, American Journal of Surgery, vol. 107, Jan. 1964, 97-103.Applicant
Pugsley, M.K. et al, The Vascular System an Overview of Structure and Function, Journal of Pharmacological and Toxicological Methods 44 (2000) 333-340.Applicant
Rippy, Marian K. et al, Catheter-Based Renal Sympathetic Denervation: Chronic Preclinical Evidence for Renal Artery Safety, Clin Res Cardiol (2011) 100:1095-1101.Applicant
Ritz, Eberhard, New Approaches to Pathogenesis and Management of Hypertension, Clin J Am Soc Nephrol 4: 1886-1891, 2009.Applicant
Robbins, Ivan M. et al, Pulmonary Vein Stenosis After Catheter Ablation of Atrial Fibrillation, Circulation Journal of the American Heart Association, 1998;98:1769-1775.Applicant
Rocha-Singh, Krishna J., Catheter-Based Sympathetic Renal Denervation A Novel Strategy for the Treatment of Resistant Hypertension, Endovascular Today, Aug. 2009, 52-56.Applicant
Rocha-Singh, Krishna J., Renal Artery Denervation: A Brave New Frontier, Endovascular Today, Feb. 2012, 45-53.Applicant
Sanderson, John E. et al, Effect of B-Blockade on Baroreceptor and Autonomic Function in Heart Failure, Clinical Science (1999) 96, 137-146.Applicant
Schauerte, Patrick et al, Catheter Ablation of Cardiac Autonomic Nerves for Prevention of Vagal Atrial Fibrillation, Circulation Journal of The American Heart Association, 2000, 102:2774-2780.Applicant
Schlaich, Markus P. et al, Renal Denervation as a Therapeutic Approach for Hypertension Novel Implications for an Old Concept, Hypertension Journal of The American Heart Association, 2009;54:1195-1201.Applicant
Schlaich, Markus P. et al, Renal Sympathetic-Nerve Ablation for Uncontrolled Hypertension, The New England Journal of Medicine, 2009; 361:932-934.Applicant
Schmieder, Roland E. et al, ESH Position Paper: Renal Denervation—An Iterventional Therapy of Resistant Hypertension, Journal of Hypertension, 2012, 30:837-841.Applicant
Sellers, Alfred M. et al, Adrenalectomy and Sympathectomy for Hypertension Ten Year Survival, Archives of Surgery, vol. 89, Nov. 1964, 880-886.Applicant
Sen, S.K., Some Observations on Decapsulation and Denervation of the Kidney, The British Journal of Urology, vol. 8, Issue 4, Dec. 1936, 319-328.Applicant
Shiraki, Iwao William, Correction of Renal Hypertension by Ligation of Stenotic Segmental Renal Artery, Urology, vol. IX, No. 3, Mar. 1977, 296-298.Applicant
Shonai, Takaharu et al, Renal Artery Aneurysm: Evaluation with Color Doppler Ultrasonography Before and After Percutaneous Transarterial Embolization, J Ultrasound Med 19:277-280, 2000.Applicant
Silver, Donald et al, Renovascular Hypertension From Renal Artery Compression by Congenital Bands, Annals of Surgery, Feb. 1976, 161-166.Applicant
Smith, Gardner W. et al, Surgical Results and the Diagnostic Evaluation of Renovascular Hypertension, Annals of Surgery, May 1968, 669-680.Applicant
Brinkmann, Julia et al, Catheter-Based Renal Nerve Ablation and Centrally Generated Sympathetic Activity in Difficult-to-Control Hypertensive Patients Prospective Case Series, Hypertension. 2012;60:1485-1490.Applicant
Jin, Yu et al, No Support for Renal Denervation in a Meta-Analysis, JACC vol. 62, No. 21, 2013 Correspondence Nov. 19/26, 2013:2029-30.Applicant
Howard, James P. et al, Size of Blood Pressure Reduction from Renal Denervation: Insights from Meta-Analysis of Antihypertensive Drug Trials of 4121 Patients with Focus on Trial Design: the Converge Report, Heart 2013;0:1-9.Applicant
Mahfoud, Felix et al, Expert Consensus Document from the European Society of Cardiology on Catheter-Based Renal Denervation, European Heart Journal, Jul. 2013;34(28):2149-57.Applicant
Howell, Marcus H. et al, Tandem Stenting of Crossed Renal Arteries with Ostial Stenosis, Tex Heart Inst J. 2000; 27(2): 166-169.Applicant
Gafoor, Sameer et al, Nonresponders to Renal Denervation for Resistant Hypertension, Endovascular Today, Oct. 2013,63-70.Applicant
Vonend, Oliver et al, Secondary Rise in Blood Pressure After Renal Denervation, The Lancet, vol. 380, Issue 9843, p. 778, Aug. 25, 2012.Applicant
Kaltenbach, Benjamin et al, Renal Artery Stenosis After Renal Sympathetic Denervation, J Am Coll Cardiol. Dec. 25, 2012;60(25):2694-5.Applicant
McGahan, John P. et al, History of Ablation, Tumor Ablation, 2005, pp. 3-16.Applicant
Schlaich, Markus P. et al, International Expert Consensus Statement: Percutaneous Transluminal Renal Denervation for the Treatment of Resistant Hypertension, Journal of the American College of Cardiology vol. 62, Issue 22, Dec. 3, 2013, pp. 2031-2045.Applicant
Crile, George, The Clinical Results of Celiac Ganglionectomy in the Treatment of Essential Hypertension, Annals of Surgery, Jun. 1938; 107(6): 909-916.Applicant
Lambert, Gavin W. et al, Health-Related Quality of Life After Renal Denervation in Patients With Treatment-Resistant Hypertension, Hypertension. 2012;60:1479-1484.Applicant
Labeit, Alexander Michael et al, Changes in the Prevalence, Treatment and Control of Hypertension in Germany? A Clinical-Epidemiological Study of 50.000 Primary Care Patients, Plos One, Dec. 2012, vol. 7, Issue 12, e52229, 1-11.Applicant
Hoppe, Uta C. et al, Minimally Invasive System for Baroreflex Activation Therapy Chronically Lowers Blood Pressure with Pacemaker-like Safety Profile: Results from the Barostim Neo Ttrial, J Am Soc Hypertens. Jul.-Aug. 2012;6 (4):270-6.Applicant
Bakris, George L. et al, Baroreflex Activation Therapy Provides Durable Benefit in Patients with Resistant Hypertension: Results of Long-Term Follow-up in the Rheos Pivotal Trial, J Am Soc Hypertens. Mar.-Apr. 2012;6 (2):152-8.Applicant
Krum, Henry et al, Device-Based Antihypertensive Therapy: Therapeutic Modulation of the Autonomic Nervous System, Circulation. 2011;123:209-215.Applicant
Howard, James P. et al, Unintentional Overestimation of an Expected Antihypertensive Effect in Drug and Device Trials: Mechanisms and Solutions, International Journal of Cardiology, vol. 172, Issue 1, Mar. 1, 2014, pp. 29-35.Applicant
Thomas, Natalie A., Secondary Consideration in Nonobviousness Analysis: The Use of Objective Indicia Following KSR V. Teleflex, NYU Law Review, vol. 86, No. 6, Dec. 2011, 2070-2112.Applicant
Campese, Vito M., Interventional Hypertension: A New Hope or a New Hype? The Need to Redefine Resistant Hypertension, J Hypertens. Nov. 2013;31(11):2118-21.Applicant
Katholi, Richard E. et al, Role of the Renal Nerves in the Pathogenesis of One-Kidney Renal Hypertension in the Rat, Hypertension. 1981;3:404-409.Applicant
Dailey, U.G., The Surgical Treatment of Hypertension: A Review, Journal of the National Medical Association, Mar. 1948, vol. 40, No. 2, 76-79.Applicant
Dailey, U.G., Surgical Treatment of Hypertension: A Review-Part II, Journal of the National Medical Association, May 1948, vol. 40, No. 3., 113-116.Applicant
Dailey, U.G., Surgical Treatment of Hypertension: A Review-Part III, Journal of the National Medical Association, Jul. 1948, vol. 40, No. 4, 160-162.Applicant
Carlstedt, Thomas et al, Regrowth of Lesioned Dorsal Root Nerve Fibers into the Spinal Cord of Neonatal Rats, Neuroscience Letters Feb. 10, 1987;74(1):14-8.Applicant
Page, Irvine H. et al, The Effects of Renal Denervation on Patients Suffering from Nephritis, J Clin Invest. 1935;14 (4):443-458.Applicant
Litynski, Grzegorz S., Kurt Semm and the Fight against Skepticism: Endoscopic Hemostasis, Laparoscopic Appendectomy, and Semm's Impact on the “Laparoscopic Revolution”, JSLS. Jul.-Sep. 1998; 2(3): 309-313.Applicant
Putney, John Paul, Are Secondary Considerations Still “Secondary”?:An Examination of Objective Indicia of Nonobivousness Five Years After KSR, Intellectual Property Brief, vol. 4, Issue 2, Article 5, 2012, 45-59.Applicant
Katholi, Richard E. et al, The Role of Renal Sympathetic Nerves in Hypertension: Has Percutaneous Renal Denervation Refocused Attention on Their Clinical Significance?; Progress in Cardiovascular Disease 52 (2009) 243-248.Applicant
Hall, John E., The Kidney, Hypertension, and Obesity, Hypertension. 2003;41:625-633.Applicant
Pavlovich, Christian P. et al, Percutaneous Radio Requency Ablation of Small Renal Tumors: Initial Results; The Journal of Urology, vol. 167, 10-15, Jan. 2002.Applicant
Kassab, Salah et al, Renal Denervation Attenuates the Sodium Retention and Hypertension Associated with Obesity, Hypertension vol. 25, No. 4, Part 2 Apr. 1995.Applicant
Grassi, Guido et al, Dissociation Between Muscle and Skin Sympathetic Nerve Activity in Essential Hypertension, Obesity, and Congestive Heart Failure, Hypertension. 1998;31:64-67.Applicant
Goldberg, Michael R. et al, Reconstructive Vascular Surgery for Renovascular Hypertension, Can Med Assoc J. Feb. 2, 1974;110(3):275-80.Applicant
Dibona, Gerald F., Role of the Renal Nerves in Renal Sodium Retention and Edema Formation, Trans Am Clin Climatol Assoc. 1990; 101: 38-45.Applicant
Michaelis, Lawrence L. et al, Effects of Renal Denervation and Renin Depletion on the Renal Responses to Intravascular Volume Expansion, Ann Surg. Mar. 1972; 175(3): 424-430.Applicant
Jaff, Michael R. et al, Kidney Stenting Lowers Blood Pressure in Patients with Severe Hypertension; Catheterization and Cardiovascular Interventions; Published Online: Jun. 27, 2012 (DOI: 10.1002/ccd.24449); Print Issue Date: Sep. 2012. URL: http://onlinelibrary.wiley.com/doi/10.1002/ccd.24449/abstract.Applicant
Luscher, Thomas F. et al, Renal Nerve Ablation After Symplicity HTN-3: Confused at the Higher Level?; European Heart Journal, doi:10.1093/eurheartj/ehu195; May 14, 2014.Applicant
Savard, Sebastien et al, Eligibility for Renal Denervation in Patients With Resistant Hypertension When Enthusiasm Meets Reality in Real-Life Patients, J Am Coll Cardiol. 2012;60(23):2422-2424.Applicant
Thiebot, J. et al, Bilateral Nephrectomy by Embolization of the Renal Arteries: A Report on Five Cases (author's transl), Sem Hop. Apr. 8-15, 1980;56(13-14):670-5.Applicant
Stuart, Candace, Newest Frontier in Cardiac Care: Kidneys; Cardiovascular Business, Dec. 13, 2012.Applicant
Stuart, Mary, Masterminds of Ardian: An Interview With Inventors Mark Gelfand and Howard Levin, Windhover Information, Start-Up Jan. 1, 2011.Applicant
Moss, Jonathan, Interventional Radiology and Renal Denervation, Interventions, vol. 13, Issue 3, 2013.Applicant
Medtronic, Inc., Scientific Basis Behind Renal Denervation for the Control of Hypertension, Dec. 2012, http:// www.icimeeting.com/2012/images/stories/PDF/1448—Wilcox—l—Mon.pdf.Applicant
Dibona, Gerald F., Sympathetic Nervous System and the Kidney in Hypertension, Curr Opin Nephrol Hypertens. Mar. 2002;11(2):197-200.Applicant
Hamm, Christian et al, Confluence, Issue eight, Apr. 2014.Applicant
Parmar, Arundhati, Analyst: Medtronic Will Likely Acquire Another Hypertension Therapy Firm, Medcity News, Apr. 27, 2012; 3:06 p.m.; medcitynews.com.Applicant
Medtronic, Inc., RDN Therapy with the Symplicity Renal Denervation System, Procedure Fact Sheet, www.medtronic.com, 2011.Applicant
Ardian, Inc., Ardian(R) Receives 2010 EuroPCR Innovation Award and Demonstrates Further Durability of Renal Denervation Treatment for Hypertension, PR Newswire, Jun. 3, 2010.Applicant
Medtronic, Inc., Medtronic Announces U.S. Renal Denervation Pivotal Trial Fails to Meet Primary Efficacy Endpoint While Meeting Primary Safety Endpoint, www.medtronic.com, Jan. 9, 2014.Applicant
Oz, Mehmet, Pressure Relief, Time Magazine, Monday, Jan. 9, 2012.Applicant
Medtronic, Inc., J.P. Morgan Healthcare Conference, Corrected Transcript, Jan. 13, 2014, Factset:Callstreet, www.callstreet.com.Applicant
Hafkenschiel, Joseph H. et al, The Surgical Treatment of Hypertension with Particular Reference to Andrenalectomy and Sympathectomy, Transactions. American College of Cardiology, vol. 5, Dec. 1955, pp. 107-112.Applicant
Smithwick, R.H., An Evaluation of the Surgical Treatment of Hypertension, The Bulletin, Nov. 1949; 25(11):698-716.Applicant
Smithwick, Reginald H. et al, Splanchnicectomy for Essential Hypertension, The Journal of the American Medical Association, vol. 152, No. 16, Aug. 1953, 1501-1504.Applicant
Solis-Herruzo, J.A. et al, Effects of Lumbar Sympathetic Block on Kidney Function in Cirrhotic Patients with Hepatorenal Syndrome, Journal of Hepatology, 1987; 5: 167-173.Applicant
Sowers, James R. et al, Diabetes, Hypertension, and Cardiovascular Disease: An Update, Hypertension Journal of The American Heart Association, 2001;37:1053-1059.Applicant
Stanley, James C., Surgical Treatment of Renovascular Hypertension, The American Journal of Surgery, vol. 174, Aug. 1997, 102-110.Applicant
Stella, Andrea et al, Effects of Reversible Renal Denervation on Haemodynamic and Excretory Functions of the Ipsilateral and Contralateral Kidney in the Cat, Journal of Hypertension 1986, 4: 181-188.Applicant
Sun, Yingxian et al, Risk of Coronary Stenosis with Venous Ablation for Epicardial Accessory Pathways, PACE, Apr. 2001, Part II, vol. 24, 605.Applicant
Swartz, John F. et al, Radiofrequency Endocardial Catheter Ablation of Accessory Atrioventricular Pathway Atrial Insertion Sites, Circulation Journal of The American Heart Association, 1993;87:487-499.Applicant
Teigen, Corey L. et al, Segmental Renal Artery Embolization for Treatment of Pediatric Renovascular Hypertension, Journal of Vascular and Interventional Radiology, 1992; 3:111-117.Applicant
Teixeira, Maria Do Carmo et a1,1992; Role of the Peripheral Renin Profile in Predicting Blood Pressure Control After Bilateral Nephrectomy in Renal-Transplanted Patients, Nephrol Dial Transplant (1998) 13: 2092-2097.Applicant
Teo, W S et al, Radiofrequency Catheter Ablation of Accessory Pathways: The Initial Experience in Singapore, Singapore Medical Journal, 1994; vol. 35:36-40.Applicant
Thomas, George et al, Renal Denervation to Treat Resistant Hypertension: Guarded Optimism, Cleveland Clinic Journal of Medicine, vol. 79, No. 7, Jul. 2012, 501-510.Applicant
Ting, Chih-Tai et al, Arterial Hemodynamics in Human Hypertension Effects of Angiotensin Converting Enzyme Inhibition, Hypertension Journal of The American Heart Association, 1993;22:839-846.Applicant
Uchida, Fumiya et al, Effect of Radiofrequency Catheter Ablation on Parasympathetic Denervation: A Comparison of Three Different Ablation Sites, PACE, vol. 21, Nov. 1998, Part II, 2517-2521.Applicant
Valente, John F. et al, Laparoscopic Renal Denervation for Intractable ADPKD-Related Pain, Nephrol Dial Transplant (2001) 16:160.Applicant
Villarreal, Daniel et al, Effects of Renal Denervation on Postprandial Sodium Excretion in Experimental Heart Failure, American Journal of Physiology, May 1994;266(5 Pt 2):R1599-R1604.Applicant
Vujaskovic, Z. et al, Effects of Intraoperative Hyperthermia on Canine Sciatic Nerve: Histopathologic and Morphometric Studies, Int. J. Hyperthermia, 1994, vol. 10, No. 6, 845-855.Applicant
De Wardener, H.E., The Hypothalamus and Hypertension, Physiological Reviews,vol. 81, No. 4, Oct. 2001.Applicant
Webb, R.L. et al, Functional Identification of the Central Projections of Afferent Renal Nerves, Clin. and Exper.—Theory and Practice, Ag(Suppl.I), 47-57 (1987).Applicant
Weinstock, Marta et al, Renal Denervation Prevents Sodium Retention and Hypertension in Salt-Sensitive Rabbits with Genetic Baroreflex Impairment, Clinical Science (1996) 90, 287-293.Applicant
Wilcox, Josiah N., Scientific Basis Behind Renal Denervation for the Control of Hypertension, Medtronic, Inc., Dec. 2012, 38 pages.Applicant
Winternitz, Sherry R. et al, Role of the Renal Sympathetic Nerves in the Development and Maintenance of Hypertension in the Spontaneously Hypertensive Rat, Journal of Clinical Investigation, vol. 66 Nov. 1980, 971-978.Applicant
Wyss, J.M. et al, Sensory Denervation of the Kidney Attenuates Renovascular Hypertension in the Rat, Am J Physiol Heart Circ Physiol 250:H82-H86, 1986.Applicant
Yamada, Yutaka et al, Age-Related Changes in Muscle Sympathetic Nerve Activity in Essential Hypertension, Hypertension Journal of the American Heart Association, 1989;13:870-877.Applicant
Zazgornik, Jan et al, Bilateral Nephrectomy: The Best, but Often Overlooked, Treatment for Refractory Hypertension in Hemodialysis Patients, AJH 1998; 11:1364-1370.Applicant
Esler, Murray D. et al, Renal Sympathetic Denervation in Patients with Treatment-Resistant Hypertension (The Symplicity HTN-2 Trial): A Randomised Controlled Trial, Lancet, 2010; 376:1903-1909.Applicant
Worthley, Stephen G. et al, Renal Denervation: How Do You Measure Success?, presentation 28 pages.Applicant
International Search Report and Written Opinion for Application No. PCT/US2010/054637.Applicant
International Search Report and Written Opinion for Application No. PCT/US2010/054684.Applicant
Perry, C. Bruce, Malignant Hypertension Cured by Unilateral Nephrectomy, British Heart Journal, Jul. 1945; 7(3): 139-142.Applicant
Ramsay, Lawrence E. et al, Blood Pressure Response to Percutaneous Transluminal Angioplasty for Renovascular Hypertension: An Overview of Published Series; British Medical Journal Mar. 3, 1990; 300(6724): 569-572.Applicant
Page, Irvine H. et al, Mechanisms, Diagnosis and Treatment of Hypertension of Renal Vascular Origin; Annals of Internal Medicine, Aug. 1959;51:196-211.Applicant
Canadian Agency for Drugs and Technologies in Health, Catheter-Based Renal Denervation for Treatment-Resistant Hypertension; Issues in Emerging Health Technologies, Issue 121, Mar. 2013.Applicant
Meredith, I T et al, Exercise Training Lowers Resting Renal But Not Cardiac Sympathetic Activity in Humans; Hypertension Journal of the American Heart Association, 1991;18:575-582.Applicant
Garel, L. et al, Fatal Outcome After Ethanol Renal Ablation in Child with End-Stage Kidneys; AJR 146:593-594, Mar. 1986.Applicant
Oparil, Suzanne et al, Renal Nerve Ablation: Emerging Role in Therapeutics; Blood Pressure, Oct. 2011, vol. 20, No. 5 , pp. 253-255.Applicant
Dibona, Gerald F., Sympathetic Nervous System and Hypertension, Hypertension Journal of The American Heart Association, 2013; 61: 556-560.Applicant
Persu, Alexandre et al, Renal Denervation: Ultima Ratio or Standard in Treatment-Resistant Hypertension, Hypertension Journal of The American Heart Association, Sep. 2012;60(3):596-606.Applicant
Doumas, Michael et al, Interventional Management of Resistant Hypertension, The Lancet, vol. 373, Apr. 11, 2009, pp. 1228-1230.Applicant
Schmieder, Roland E. et al, Updated EHS Position Paper on Interventional Therapy of Resistant Hypertension, EuroIntervention 2013; 9:R58-R66.Applicant
Calleary, Hickey D. et al, Pre-Transplant Bilateral Native Nephrectomy for Medically Refractory Hypertension, The Irish Medical Journal, Jul.-Aug. 2001;94(7):214-6.Applicant
Davis, Mark I. et al, Effectiveness of Renal Denervation Therapy for Resistant Hypertension A Systematic Review and Meta-Analysis, Journal of the American College of Cardiology, vol. 62, No. 3, 2013, 231-241.Applicant
Blankestijn, Peter J. et al, Renal Denervation: Potential Impact on Hypertension in Kidney Disease?, Nephrol Dial Transplant (2011) 0: 1-3.Applicant
Bernardi, Luciano et al, Influence of Type of Surgery on the Occurrence of Parasympathetic Reinnervation After Cardiac Transplantation, Circulation Journal of the American Heart Association, Apr. 14, 1998;97(14):1368-74.Applicant
Smith, Harold P. et al, Radiofrequency Neurolysis in a Clinical Model Neuropathological Correlation, J Neurosurg 55:246-253, 1981.Applicant
Young, Robert R. et al, Reversible Block of Nerve Conduction by Ultrasound Ultrasonic Blocking of Nerve Fibers, Arch Neurol. 1961;4(1):83-89.Applicant
Wolf-Maier, Katharina et al, Hypertension Treatment and Control in Five European Countries, Canada, and the United States, Hypertension. 2004;43:10-17.Applicant
Elmula, Fadl et al, Renal Sympathetic Denervation in Patients With Treatment-Resistant Hypertension After Witnessed Intake of Medication Before Qualifying Ambulatory Blood Pressure, Hypertension. 2013;62:526-532.Applicant
Santos, Mario et al, Renal Sympathetic Denervation in Resistant Hypertension, World J Cardiol Apr. 26, 2013; 5(4): 94-101.Applicant
Hafkenschiel, Joseph H. et al, Primary Hypertension Survey of the Survival of Patients with Established Diastolic Hypertension After Ten Years of Medical and Surgical Treatment, The American Journal of Cardiology, vol. 16, Jul. 1965, 61-66.Applicant
Hall, Winthrop H. et al, Combined Embolization and Percutaneous Radiofrequency Ablation of a Solid Renal Tumor, American Journal of Roentgenology, 174, Jun. 2000, 1592-1594.Applicant
Hall, J.E. et al, Role of Sympathetic Nervous System and Neuropeptides in Obesity Hypertension, Brazilian Journal of Medical and Biological Research, 2000, 33:605-618.Applicant
Han, Young-Min et al, Renal Artery Embolization with Diluted Hot Contrast Medium: An Experimental Study, Journal of Vascular and Interventional Radiology, Jul. 2001;12(7):862-868.Applicant
Hansen, Jesper Melchoir et al, The Transplanted Human Kidney Does Not Achieve Functional Reinnervation, Clinical Science, (1994) 87, 13-20.Applicant
Heuer, George J., The Surgical Treatment of Essential Hypertension, Annals of Surgery, Oct. 1936, vol. 104, No. 3, 771-786.Applicant
Hinton, J. William, End Results of Thoracolumbar Sympathectomy for Advanced Essential Hypertension, The Bulletin, Apr. 1948, 239-252.Applicant
Holmer, Stephan et al, Role of Renal Nerves for the Expression of Renin in Adult Rat Kidney, The American Journal of Physiology, May 1994;266(5 Pt 2):F738-F745.Applicant
Hoobler, S.W. et al, The Effects of Splanchnicectomy on the Blood Pressure in Hypertension, Circulation Journal of The American Heart Association, vol. IV, Aug. 1951, 173-183.Applicant
Hoye, Neil A. et al, Endovascular Renal Denervation: A Novel Sympatholytic with Relevance to Chronic Kidney Disease, Clinical Kidney Journal Advance Access, (2013) 0: 1-8.Applicant
Huang, Wann-Chu, Renal Denervation Prevents and Reverses Hyperinsulinemia-Induced Hypertension in Rats, Hypertension Journal of The American Heart Association, 1998;32:249-254.Applicant
Huang, Shoei K. Stephen et al, Radiofrequency Catheter Ablation of Cardiac Arrhythmias, Basic Concepts and Clinical Applications, Wiley-Blackwell, Jun. 2000, 1-12.Applicant
Humpreys, Michael H., Renal Nerves and CKD: Is Renal Denervation the Answer?, Journal of The American Socity of Nephrology, 2012, 23: 1-3.Applicant
Irigoyen, M.C.C. et al, Baroreflex Control of Sympathetic Activity in Experimental Hypertension, Brazilian Journal of Medical and Biological Research, (1998) 31: 1213-1220.Applicant
Izzo, Jr, Joseph L. et al, The Sympathetic Nervous System and Baroreflexes in Hypertension and Hypotension, Current Hypertension Reports 1999, 3:254-263.Applicant
Jackman, Warren M. et al, Catheter Ablation of Arrhythmias, Proposed Anatomy and Catheter Ablation of Epicardial Posteroseptal and Left Posterior Accessory AV Pathways (Chapter 16), 2002, Futura Publishing Company, Inc., 321-343.Applicant
Jain, Mudit K. et al, A Three-Dimensional Finite Element Model of Radiofrequency Ablation with Blood Flow and Its Experimental Validation, Annals of Biomedical Engineering, vol. 28, pp. 1075-1084, 2000.Applicant
Jais, Pierre et al, Efficacy and Safety of Septal and Left-Atrial Linear Ablation for Atrial Fibrillation, The American Journal of Cardiology, vol. 84 (9A), Nov. 1999, 139R-146R.Applicant
Janssen, Ben J.A. et al, Frequency-Dependent Modulation of Renal Blood Flow by Renal Nerve Activity in Conscious Rabbits, American Journal of Physiology, 1997, 273:R597-R608.Applicant
Janssen, Ben J.A. et al, Renal Nerves in Hypertension, Miner Electrolyte Metab 1989;15:74-82.Applicant
Kaltenbach, Benjamin et al, Renal Sympathetic Denervation as Second-Line Therapy in Mild Resistant Hypertension: A Pilot Study, Catheterization and Cardiovascular Interventions 81:335-339 (2013).Applicant
Kamiya, Atsunori et al, Parallel Resetting of Arterial Baroreflex Control of Renal and Cardiac Sympathetic Nerve Activities During Upright Tilt in Rabbits, Am J Physiol Heart Circ Physiol 298: H1966-H1975, 2010.Applicant
Kandzari, David E. et al, Catheter-Based Renal Denervation for Resistant Hypertension: Rationale and Design of the Symplicity HTN-3 Trial, Clin. Cardiol. 35, 9, 528-535 (2012).Applicant
Kapural, Leonardo et al, Radiofrequency Ablation for Chronic Pain Control, Current Pain and Headache Reports 2001, 5:517-525.Applicant
Katholi, Richard E. et al, Decrease in Peripheral Sympathetic Nervous System Activity following Renal Denervation or Unclipping in the One-Kidney One-Clip Goldblatt Hypertensive Rat, The Journal of Clinical Investigation, Jan. 1982;69(1):55-62.Applicant
Katritsis, Demosthenes et al, Recurrence of Left Atrium-Pulmonary Vein Conduction Following Successful Disconnection in Asymptomatic Patients, Europace (2004) 6, 425e432.Applicant
Killip III, Thomas, Oscillation of Blood Flow and Vascular Resistance During Mayer Waves, Circulation Research, vol. XI, Dec. 1962, 987-993.Applicant
Kingwell, Bronwyn A. et al, Assessment of Gain of Tachycardia and Bradycardia Responses of Cardiac Baroreflex, Am J Physiol Heart Circ Physiol 260:H1254-H1263, 1991.Applicant
Kirchheim, H. et al, Sympathetic Modulation of Renal Hemodynamics, Renin Release and Sodium Excretion, Klin Wochenschr (1989) 67: 858-864.Applicant
Klein, GE et al, Endovascular Treatment of Renal Artery Aneurysms with Conventional Non-Detachable Microcoils and Guglielmi Detachable Coils, Br J Urol. Jun. 1997; 79(6):852-860.Applicant
Knight, Eric L. et al, Predictors of Decreased Renal Function in Patients with Heart Failure During Angiotensin-Converting Enzyme Inhibitor Therapy: Results from the Studies of Left Ventricular Dysfunction (SOLVD), American Heart Journal, vol. 138, No. 5, Part 1, Nov. 1999, 849-855.Applicant
Koepke, John P. et al, Functions of the Renal Nerves, The Physiologist, vol. 28, No. 1, Feb. 1985, 47-52.Applicant
Kompanowska-Jezierska, Elzbieta et al, Early Effects of Renal Denervation in the Anaesthetised Rat: Natriuresis and Increased Cortical Blood Flow, Journal of Physiology (2001), 531.2, pp. 527-534.Applicant
Krum, Henry et al, Catheter-Based Renal Sympathetic Denervation for Resistant Hypertension: A Multicentre Safety and Proof-of-Principle Cohort Study, www.thelancet.com vol. 373 Apr. 11, 2009 1275-1281.Applicant
La Grange, Ronald G. et al, Selective Stimulation of Renal Nerves in the Anesthetized Dog: Effect on Renin Release During Controlled Changes in Renal Hemodynamics, Circulation Research, Journal of the American Heart Association, 1973;33:704-712.Applicant
Labonte, Sylvain, Numerical Model for Radio-Frequency Ablation of the Endocardium and its Experimental Validation, IEEE Transactions on Biomedical Engineering, vol. 41, No. 2. Feb. 1994, 108-115.Applicant
Lee, Sang Joon et al, Ultrasonic Energy in Endoscopic Surgery, Yonsei Medical Journal, vol. 40, No. 6, pp. 545-549, 1999.Applicant
Leertouwer, Trude C. et al, In-Vitro Validation, with Histology, of Intravascular Ultrasound in Renal Arteries, Journal of Hypertension 1999, vol. 17 No. 2, 271-277.Applicant
Leishman, A.W.D., Hypertension—Treated and Untreated, British Medical Journal, May 1959, 1361-1368.Applicant
Leonard, Bridget L. et al, Differential Regulation of the Oscillations in Sympathetic Nerve Activity and Renal Blood Flow Following Volume Expansion, Autonomic Neuroscience: Basic and Clinical 83 (2000) 19-28.Applicant
Levin, Stephen, Ardian: Succeeding Where Drugs Fail Treating Hypertension in the Cath Lab, In Vivo: The Business & Medicine Report, vol. 27, No. 10, Nov. 2009.Applicant
Lu, David S.K. et al, Effect of Vessel Size on Creation of Hepatic Radiofrequency Lesions in Pigs: Assessment of the “Heat Sink” Effect, American Journal of Radiology, 178, Jan. 2002, 47-51.Applicant
Lustgarten, Daniel L. et al, Cryothermal Ablation: Mechanism of Tissue Injury and Current Experience in the Treatment of Tachyarrhythmias, Progress in Cardiovascular Diseases, vol. 41, No. 6 (May/Jun. 1999): pp. 481-498.Applicant
Mancia, Giuseppe et al, Sympathetic Activation in the Pathogenesis of Hypertension and Progression of Organ Damage, Hypertension Journal of The American Heart Association, 1999, 34:724-728.Applicant
Medtronic, Inc., Renal Denervation (RDN) Novel Catheter-based Treatment for Hypertension, Symplicity RDN System Common Q&A, 2011.Applicant
Mehdirad, Ali et al, Temperature Controlled RF Ablation in Canine Ventricle and Coronary Sinus using 7 Fr or 5 Fr Ablation Electrodes, PACE, vol. 21, Jan. 1998, Part II, 316-321.Applicant
Millard, F.C. et al, Renal Embolization for Ablation of Function in Renal Failure and Hypertension, Postgraduate Medical Journal (1989) 65, 729-734.Applicant
Moak, Jeffrey P. et al, Case Report: Pulmonary Vein Stenosis Following RF Ablation of Paroxysmal Atrial Fibrillation: Successful Treatment with Balloon Dilation, Journal of Interventional Cardiac Electrophysiology, Dec. 2000, 4, 4:621-631.Applicant
Mogil, Robert A. et al, Renal Innervation and Renin Activity in Salt Metabolism and Hypertension, American Journal of Physiology, vol. 216, No. 4, Apr. 1969, 693-697.Applicant
Morita, Hironobu et al, Neural Control of Urinary Sodium Excretion During Hypertonic NaC1 Load in Conscious Rabbits: Role of Renal and Hepatic Nerves and Baroreceptors, Journal of the Autonomic Nervous System, 34 (1991) 157-170.Applicant

Abstract