|Publication number||WO2001087172 A1|
|Publication date||22 Nov 2001|
|Filing date||14 May 2001|
|Priority date||12 May 2000|
|Also published as||CA2408176A1, CN1440258A, CN100506183C, DE60136535D1, EP1280467A1, EP1280467B1, EP1280467B8, US6936047, US20040006337, WO2001087172A9|
|Publication number||PCT/2001/15346, PCT/US/1/015346, PCT/US/1/15346, PCT/US/2001/015346, PCT/US/2001/15346, PCT/US1/015346, PCT/US1/15346, PCT/US1015346, PCT/US115346, PCT/US2001/015346, PCT/US2001/15346, PCT/US2001015346, PCT/US200115346, WO 0187172 A1, WO 0187172A1, WO 2001/087172 A1, WO 2001087172 A1, WO 2001087172A1, WO-A1-0187172, WO-A1-2001087172, WO0187172 A1, WO0187172A1, WO2001/087172A1, WO2001087172 A1, WO2001087172A1|
|Inventors||Michael Nasab, Eric K. Y. Chan|
|Export Citation||BiBTeX, EndNote, RefMan|
|Patent Citations (4), Referenced by (19), Classifications (18), Legal Events (10)|
|External Links: Patentscope, Espacenet|
MULTI-CHANNEL RF ENERGY DELIVERY WITH COAGULUM REDUCTION
BACKGROUND OF THE INVENTION Radio frequency energy may be used to treat certain cardiac abnormalities, such as fibrillation, by ablating caridiac tissue. Radio frequency energy is delivered by RF generators in two phases: (i) the "ramp up" phase in which a relatively high amount of power is delivered to the ablating electrode until a desired set temperature is sensed by the thermocouple or thermistor, and (ii) the "regulation" phase in which power is still being delivered but regulated at a lower level to maintain the desired set temperature. This target temperature is predetermined by the operator, and is generally 50° to 55° C for ablation of cardiac tissue.
Most RF generators have software modules which run simultaneously on portable computers during RF energy delivery to log the ablation episode. Typically, the parameters logged are sensed impedance, power delivered, as well as tissue temperature sensed by either thermistors or thermocouples. Currently, this information is typically used for post-procedural review.
The challenge in RF ablation of cardiac tissue is to create deep lesions in the cardiac tissue while avoiding coagulum formation. It follows that RF energy must be delivered efficiently into the tissue, and not delivered and lost into the blood medium. Current methods and systems are not adequate to assure that RF energy is delivered efficiently to cardiac tissue during an ablation procedure.
Prior studies in the delivery of RF energy have shown that when electrode- tissue contact is intermittent, the impedance value fluctuates and the power delivered also has to rapidly adapt in order to reach or maintain the target temperature. The rapid alternating impedance values therefore cause the output power waveform to also fluctuate rapidly. If the rise-time of the RF power waveform is sharp, and the noise modulated onto the RF source signal has high enough amplitude, it may be conducive for coagulum formation because it may undesirably approximate the coagulation waveform used by electro-surgical units. Therefore, there remains a need for systems and methods for performing RF ablation wherein effective contact with target cardiac tissue is assured to achieve deeper lesions and reduced coagulum formation.
The methods and systems of the current invention provide efficient delivery of radio frequency (RF) energy to cardiac tissue with an ablation catheter, thereby yielding consistently effective RF ablation procedures and improved patient outcomes.
Summary of the Invention
The methods and systems of the current invention deliver RF energy to cardiac tissue simultaneously through a series of channels in a manner that is designed to minimize the risk of an ineffective ablation procedure due to coagulum formation. The methods and systems utilize an information processor and RF output controller to carefully control the rate and amount of RF energy delivered from an RF generator to the cardiac tissue being ablated to improve the effectiveness of an ablation procedure. The information processor and RF output controller assures that RF energy is increased gradually during the initial ramp-up phase. Furthermore, the information processor and RF output controller regulates delivery of RF energy during the ablation episode using information gathered from a series of sensors that are delivered to the site of ablation, preferably as part of an ablation catheter. The series of sensors include a series of temperature sensors and/or a multiplicity of current sensors. This feedback-control assures that proper temperature is maintained at the site of ablation and provides the ability to abort an ablation procedure if effective tissue contact is not established or maintained throughout the ablation procedure.
BRIEF DESCRIPTION OF THE DRAWINGS The novel features believed characteristic of the invention are set forth in the appended claims. The invention itself, however, as well as the preferred mode of use, further objectives and advantages thereof, is best understood by reference to the following detailed description of the embodiments in conjunction with the accompanying drawings and Appendix, wherein: FIGS. 1 A AND 1 B are schematic diagrams of certain embodiments of the information processor and RF output controller and system of the current invention (FIG. 1 A), and user interface (FIG. 1 B) for the information processor and RF output controller.
FIGS. 2A-B show catheter arrangements for efficient ablation;
FIGS. 3 and 4 show schematic block diagrams of an information processor and RF output controller in accordance with the invention, for regulating delivery of RF energy to cardiac tissue through an ablation catheter^
FIGS. 5A and 5B provide flow diagrams for the temperature measurements, and FIG. 5C is a block diagram illustrating real time analog computation of voltage impedance and power; FIG. 6 shows a schematic diagram of temperature regulation circuitry used to regulate RF energy based on temperature readings.
FIG. 7 is a block diagram showing the regulation of delivery of RF energy by an information processor and RF output controller according to one embodiment of the current invention that regulates current delivered to each ablation electrode of a series of ablation electrodes, separately using digital logic.
FIG. 8 shows a record of a typical ablation episode using the methods and procedures of the current invention; and
FIG. 9 is a graph of logistic function with estimated probability of coagulum as the Dependent Variable, and C.I. as the Predictor Variable. FIGS. 10A and 10B show representative scattergrams of coagulum index values from two RF ablation patient cases. FIG. 10A shows results from a patient study when gradual power delivery was not applied and maximum power was set at 50 W. FIG. 10B shows results from a patient study using systems and methods according to the current invention where gradual power delivery was applied for each ablation episode and maximum power of the RF generator was set at 30 W. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS The methods and systems of the current invention utilize a novel information processor and RF output controller, also called a multi-channel RF ablation interface herein, to regulate delivery of radio frequency (RF) energy from an RF generator, also called an RF energy source herein, to cardiac tissue via an electrical coupling connected to a series of ablation electrodes of an ablation catheter. The information processor and RF output controller assures that energy is delivered in a gradually increasing manner during an initial ramp-up phase to an ablation temperature set point, and at a rate thereafter that is feedback-regulated to maintain the set-point temperature of the cardiac tissue at the site of ablation. Preferably, the temperature set point is selectable by a user. The delivery of energy is also preferably feedback- regulated by other parameters such as impedance, current, and/or power delivered to the ablation catheter to assure that effective contact between the ablation electrode and the cardiac tissue is maintained.
The information processor and RF output controller of the current invention are capable of delivering energy to each electrode of the series of ablation electrodes independently. In certain preferred embodiments, described herein, the information processor and RF output controller uses analog methods for information processing and pulsewidth modulation for RF energy control.
In preferred embodiments, the information processor and RF output controller is capable of delivering RF energy to the electrodes of the series of electrodes in any order or combination using methods described herein. Preferably, a user can select the electrode, or combination of electrodes, to which the information processor and RF output controller will deliver energy.
As shown in FIG. 1 A, the described information processor and RF output controller 100, also referred to herein as a multi-channel RF ablation interface, is intended to make cardiac lesions in the human heart in conjunction with commercially available radio-frequency (RF) lesion generators (RF generators) 150 and ablation catheters 160, such as those manufactured by Cardima. The interface regulates RF energy delivery from the RF generator 150 to the ablation catheter 160 by temper- ature feedback using readings of thermocouple sensors 162 embedded in the catheters 160, as well as by other parameters such as impedance and differential impedance. Electrical communication between the information processor and RF output controller and the catheter occurs via an electrical coupling 170. The feedback regulation functions to maintain the electrode temperature near the preset temperature value, and to assure that effective contact between ablation electrodes 164 and cardiac tissue has been maintained for effective transmission of energy from the electrodes 164 to the cardiac tissue.
The general design features of the multi-channel RF ablation interface (i.e. the information processor and RF output controller) of the current invention include an operating RF frequency range of about 470 to about 510 kHz; multiple, preferably eight (8), regulated electrode channels; maximum power RF energy input of about 100 watts; maximum power RF energy output for each channel of 30 Watts; and a function that provides gradually power delivery at start-up. As described below, preferably the power for each channel is typically set at about 25 to 35 watts, most preferably about 30 watts. The information processor and RF output controller is typically capable of receiving real-time temperature monitoring information from sensors 162 on the ablation catheter 160, and compares this information with the user defined set temperature. This temperature information is used to control the titration of RF energy to reach and maintain the set temperature, or to shut off RF energy delivery if a certain over-temperature cutoff is reached. The information processor and RF output controller also calculates real-time impedance and output power based on measurements sensed from the circuitry, then compares this calculated information to user set limits, wherein if a limit is exceeded, delivery of energy is terminated. Preferably the information processor and RF output controller 100 is capable of receiving and processing this information for each output channel of the circuitry. The information processor and RF output controller may use analog or digital methods for receiving and processing monitoring information from the sensors. In a preferred embodiment real-time analog data acquisition and computation methods are used. The information processor and RF output controller and/or the RF source has the ability to deliver RF energy in a gradual manner when energy delivery is initiated. That is, either in a manual, or preferably an automated manner, upon initiation of delivery of RF energy to an ablation electrode, power is initiated at a level that is below the maximum power level used to attain a temperature set point for the cardiac tissue being ablated. Power is then gradually increased over a duration of about 8 to 15 seconds, preferably 10 seconds, typically until it reaches the maximum power. For example, but not intended to be limiting, when using the Radionics RFG-3E generator in the manual mode, power may be commenced with a setting of 10 watts, and then gradually increased within 10 seconds by adjusting the power knob on the RF generator to reach a set temperature of 50°C while not overshooting a maximum of 30 watts, all the while maintaining total RF delivery time at 60 seconds. Rather than a manually controlled mode, the preferred information processor and RF output controller and RF output controller of the current invention, as described below in more detail, gradually increases power automatically upon initiation of RF energy delivery. As shown in FIG 1B, the information processor and multichannel simultaneous
RF output controller typically contains a user interface containing a series of displays 105 and 110, and adjustment knobs 115, 120, 125, 130, 135 to facilitate monitoring and control of the parameters described above. For example, the user interface may contain a display of parameter values 105, and may preferably contain a separate thermocouple digital display 110.
The user interface typically contains a series of adjustment knobs 115, 120, 25, 130, 135 to facilitate setting values for the parameters described above. For example, the information processor and RF output controller typically includes an ablation temperature set point control 115 and over-temperature set point control 120. Typically the ablation temperature set point control 115 has a range of from about 50° C to about 70° C, and the over-temperature set point control 120 has a range from about 55° C to about 75° C. Additionally, the information processor and RF output controller preferably can determine impedance and differential impedance, typically measures power output and includes a power limit adjustment knob 125. Preferably, the information processor and RF output controller has an impedance limit control 130 which typically can be set in the range from about 50 to about 1000 Ohms. Additionally, the information processor and RF output controller preferably has a differential impedance set point control 135 from 10 to 300 Ohms.
Finally, the information processor and RF output controller user interface may contain a fault status indicator 140 which may project any type of signal detectable by a user if the information processor and RF output controller detects a parameter value that exceeds a preset limit. For example, the fault status indicator may be triggered if the temperature of the cardiac tissue exceeds a maximum temperature set by the user. The fault status indicator may project a visual or auditory signals. In certain preferred embodiments, the user interface includes a reset switch which resets the fault status indicator.
The user interface on the information processor and RF output controller may have one or more of the following additional features, as described in more detail in the specific embodiment disclosed below:
1. an ablate/pace mode select switch to switch between ablation and electro- cardiogram recording modes;
2. ablate, RF active and pace indicator LEDs;
3. a bipolar pacing stimulator selector switch;
4. a parameter display pushbutton switch;
5. an illuminated on/off electrodes select switch; and 6. a real-time parameter data collection for post processing and data analysis in commercial software programs such as, but not limited to, LabView and Excel formats.
As mentioned above, the information processor and RF output controller of the current invention regulates delivery of RF energy from an RF energy source through multiple channels simultaneously to cardiac tissue. The primary functional building block of all radio frequency (RF) energy sources developed for tissue ablation is an electronic circuit called an oscillator which generates sinusoidal waveforms at particular operating frequencies. This waveform is consequently amplified to deliver the required wattage required for tissue ablation. The operating frequency of this RF oscillator typically is within the range of 470 to 510 kHz. The quality of the oscillator and ancillary electronics design impinges on the stability of the resulting operating frequency. Hence, this operating frequency may "drift" slightly if the oscillator design is unstable. Typically, this frequency jitter has imperceptible influence on the resulting tissue lesion. However, certain RF oscillators or associated electronics systems generate and deliver a skewed or distorted sine wave signal that has spurious noise spikes and/or harmonics riding on top of it. Such "noisy" and skewed RF waveforms may result in undesirable noise artifacts may have the potential of promoting coagulum formation if they are present during the ablation process. Therefore, it is desirable for the current invention to use an RF source which produces a relatively pure and stable sine wave, preferably as pure and stable a sine wave as possible.
As described above, the information processor and RF output controller is connected to and regulates RF energy delivered to multiple electrodes arranged in various configurations at the distal end of a catheter. In catheter ablation, electrodes of the catheter deliver the RF current into biological tissue. This RF energy in turn heats the tissue by causing ionic friction within the tissue and fluid medium encompassed by the electric field. When monitored, this temperature rise caused by the conversion of electrical to thermal energy can be used as a guide in RF catheter ablation. Its measurement is facilitated by the placement of thermal sensors, either thermocouples or thermistors, underneath or juxtaposed with the ablative electrodes. Not only can the sensed temperature be used to ascertain the quality of electrode- tissue contact and predict lesion size, it can also be utilized by the RF generator as a feedback signal to automatically regulate the output power to arrive at or maintain a temperature set-point predetermined by the end-user.
Many ablation catheters are known in the art and can be used with the systems and methods of the current invention. Typically, catheters for use with the current invention have multiple electrodes and thermal sensors in close proximity to these electrodes, as discussed above. Furthermore, preferred catheters allow relatively higher electrode current densities which allow lower maximum RF generator power settings, such that effective ablation can be performed at 35 W, and more preferably 30 W, rather than 50 W.
An example of a preferred catheter (i.e., the CARDIMA Revelation™ TX 3.7 Fr catheter) for use in the current invention is illustrated in FIGS. 2A-2B. The catheter was developed for right atrial linear MAZE ablation, and has eight electrodes with thermocouples located in between the electrodes, to accurately sense localized tissue temperature at the ablation site. This preferred catheter has eight 6 mm coil electrodes with 2mm inter-electrode spacing, and 8 thermocouples located proximal to each electrode in the inter-electrode spaces. A 9 Fr steerable guiding catheter called the Naviport™ may be used in conjunction with this catheter to aid in placement. Experience with the 3.7 Fr REVELATION Tx microcatheter has shown that it is successful in creating transmural lesions narrower and with smaller surface area than those created by standard 8 Fr ablation catheters.
In order to switch between each of the multiple electrodes and their corresponding thermocouples or thermistors, manual switchboxes interfacing multi- electrode catheters to single-channel RF generators, as well as automatic sequencing multi-channel RF energy generators have been developed and are now available in the marketplace. These switchboxes and multi-channel RF generators deliver RF energy to these electrodes in a consecutive, sequential fashion. In addition, there are also newer, higher power (e.g., 150W) RF generators which deliver RF energy simultaneously to multiple electrodes. These latter systems differ in design by how RF energy "is split" among the various electrode channels. This present invention presents a multichannel RF ablation system which uses pulse width modulation to govern the amount of RF energy being delivered at each channel, incorporating temperature feedback information per channel as well as from neighboring channels.
With these general features of a system for the delivery of RF energy to cardiac tissue according to the present invention, a specific embodiment is diagrammatically illustrated in FIGS. 3 and 4. The described embodiment provides a specific multi-channel RF ablation system with the general features illustrated in FIGS. 1A and 1B. The multichannel information processor and RF energy controller provides up to eight channels (switch selectable) of precise RF energy to the catheter's electrodes as well as displays the tissue temperature and impedance in real time. Measurement of the RF power delivered to the tissue, RF current, and RF voltage, as well as the differential impedance for each of the ablation elements, is also provided. All signals are available for computer monitoring or optionally displayed via front panel digital meters. The system incorporates a medical grade power supply approved by the international safety agencies. This power supply can be used for various line voltages and frequencies without any modification. The system is designed to handle up to 100 watts of input power RF energy. Utilizing an analog computer unit (ACU), the system continuously monitors and adjusts the precise RF energy delivered to each electrode.
The following are features of the pulse width modulation implementation for the system: (1) soft start power-on operation; (2) compensation for the lag in thermocouple response time; and (3) PWM synchronization for all eight channels. Over-temperature detection is provided for each channel of the system. RF energy is latched off for the entire system if an over-temperature condition is detected. Operation is resumed by power cycling or pushbutton reset. Open thermocouple detection inhibits operation of only the faulty channel. Operation is resumed automatically when the fault is cleared. The system is designed to comply with the requirements and standards of international electrical safety codes. It utilizes isolated circuits for all patient connections to insure patient safety even with failed components. This applies to both the thermocouple amplifiers, and the RF output circuitry. The over-temperature cutoff limit is provided to cut off all power delivered to the catheter in the event that any thermocouple reaches a preset over-temperature limit. Adjustment range for this function is from 55° C. to 75° C.
A front panel control and display unit is provided which allows a user to set a number of parameters. For example, the front panel control and display can be used to set the maximum power value sent to any one electrode (Adjustment range: 1-30 watts). The impedance cutoff circuitry monitors each channel individually and will cause the power delivery to be interrupted from a given electrode when that electrode's impedance rises above a preset limit. The front panel control and display (one for the entire unit) provide a control button or knob for setting the impedance cutoff limit (Adjustment range: 50-1000 Ohms). The differential impedance cutoff circuitry monitors each channel individually and will interrupt power delivered to a given electrode if that electrode's impedance rises by a preset differential (above the lowest value during a given ablation run). The front panel control and display provides a knob for setting the differential impedance cutoff limit (Adjustment range: 10-200 Ohms). In order to prevent an RF generator trip-out due to low impedance (as can occur when several electrodes are running in parallel simultaneously), an active impedance network (dummy loads) are placed between the RF generator and the ablation circuitry.
A mode switch (ablate/pace) is provided for switching between ablation and electrocardiogram recording modes, as well as pace threshold determination mode. Appropriate filtering is designed to allow recording of electrocardiogram during ablation or pacing modes. Modes of Operation:
(Mode 1) Used for catheters that utilize thermocouples between electrodes (e.g., thermocouple 1 is proximal to thermocouple 2). The system will monitor temperature on both sides of each electrode and regulate the temperature based upon the higher temperature, except for the most distal electrode, which has only one nearest thermocouple.
(Mode 2) Used for catheters utilizing thermocouples either under or soldered directly onto each electrode. The channel card functional block diagram (FIGS. 3 and 4) of the system 10 provide thermocouple inputs and patient isolation 12, pulse width modulator 14, power output RF control 16, analog computer and parameter measurement 18, impedance" and differential impedance 20, fault latch control 22, and fault status 28.
The common mode input filter is designed to handle high common mode of RF energy level on the thermocouples. The isolation circuits, both the power supply and the thermocouple amplifiers, are designed to isolate the patient from the main power source circuitry by 2500 volts.
The pulse width modulator (PWM) 14 regulates the RF energy by comparing the delivered RF power (computed by the analog computer) to the preset value (PLIMIT). It also provides soft start for each channel card as well as synchronization circuitry for all eight channels. The soft start is a safety feature active at power on that gradually ramps up the voltage to prevent spikes on the electrodes.
As shown diagrammatically in FIGS. 5A-B, the amount of energy delivered to the RF coupling transformer is directly proportional to the pulse width generated by the PWM circuitry based on the temperature feed back from the catheter's thermocouple. In the preferred example of an ablation catheter for the current invention described above, each channel has a corresponding thermocouple (T/C) sensor which provides temperature feedback information at the tissue site immediately proximal to the electrode delivering RF energy. The RF output for each electrode is modulated by a PWM chip on the channel card. The commercially available PWM device used is the Unitrode High Speed PWM Controller UC3823, or the equivalent chip made by MicroLinear, ML4823. Temperature input signals sensed from neighboring T/C's are used to control the pulse-width modulator (PWM) outputs. The lower the input voltage corresponding to an input temperature, the longer the "on time" duration. Conversely, the higher the input voltage corresponding to a sensed input temperature, the shorter the "on time" duration.
The temperature regulation circuitry of this specific example is shown in more detail in FIG. 6. As mentioned above, each electrode 164 has a corresponding thermocouple sensor 162 that provides temperature feedback information at the tissue site immediately proximal to the electrode delivering the RF energy. Each electrode's RF output is controlled by a PWM circuit 180 located on each channel card. Temperature input signals sensed from neighboring thermocouples that are electronically subtracted from each other to form a new pulse width that will control the amount of RF energy output. For example, FIG. 6 illustrates the monitoring of both sides of electrode #5 and the resulting differential PWM that will control the RF circuitry for this electrode. As illustrated, digital logic, herein NAND gate 185 is employed with inputs set by temperature thresholds taken from thermocouples adjacent to the electrodes.
Safety features that isolate the external RF generator (coupling transformers) from the power source are implemented both on the channel card as well as common electronics board.
The voltage, current, impedance, and output power are calculated by the analog computer unit (ACU) and the associated high precision RMS to DC converter circuitry. The information generated by the ACU is crucial to the precise control and stability of the system. This provides real-time monitoring of the catheter's parameters and stabilizes the preset temperature for a constant stream of energy in order to create a clean and accurate lesion.
As shown diagrammatically in FIGS. 5 A-B, this interface provides an impedance and delta impedance cutoff for each channel individually. This will cause the power delivery to be interrupted from a given electrode when that electrode's impedance rises above a preset limit.
Over temperature, open thermocouple, high impedance, and high delta impedance detection circuitry are implemented into the design of the preferred example of an information processor and RF output controller (i.e. the IntelliTemp system) described herein. System shutdown occurs for over temperature detection on any channel. Open thermocouple will inhibit operation on the affected channel only, normal operation proceeds on remaining channels.
The following parameters are used for real time analog computation of voltage impedance and power according to the specific example of an information processor and RF output controller described above: Input parameters:
Sensed AC Voltage, Vin, via secondary side of the input transformer. Sensed AC Current, ljn, mA, via precision non-inductive resistor and associated circuitry.
Computed RMS Voltage, Vout, 100mV/RMS representing 1 Volt, V. Converted RMS Current, lout, 10mV/RMS representing 1 milliampere, mA. Computed Impedance, Zout, 1 mV/RMS representing 1 ohm, Ω.
Computed RMS Power, Pout, 100mV/RMS representing 1 Watt, W. Introduction:
The specific example of the information processor and RF output controller illustrated in FIGS. 3-7 does not rely on digital circuitry (e.g., analog-to-digital (A/D) converters, digital latches, registers, and a microprocessor) to determine sensed voltage, impedance, and power. Instead, it utilizes analog methods to provide realtime computation of RMS output, voltage, current, impedance and power.
The building blocks for the real-time analog computer are illustrated in FIG. 5C and described in the following paragraphs.
1. The primary building block for this analog computation circuitry is the Analog Devices AD538 Real-Time Analog Computation Unit (ACU) which provides precision analog multiplication, division, and exponentiation. The first two mathematical operations are used, as follows: The ACU has this transfer function:
VOUT CU = Vy(Vz/Vx) It should be noted that this VOUT.ACU 'S n°t the overall VOUT of the analog computation system; it is merely the output of the AD538 device used. Vz is a DC value that is an output parameter from the second set of building blocks mentioned below, the RMS-to-DC Converter. This DC value represents the RMS voltage (V) of the RF energy being delivered at the electrode. Similarly, Vx is a DC value which has been converted from the RMS current (mA), of the RF energy being delivered at the electrode. This device also permits a scaling factor, Vy, to be multiplied into the output transfer function. This scaling factor is set at a value of 0.1 , since the ratio of the primary to secondary coils of the input transformer is 10. Since Vz represents voltage, and Vx represents current, therefore VOUT.ACU represents the computed real-time impedance Ω.
2. The secondary building blocks are two Analog Devices AD637 High Precision Wide-Band RMS-to-DC Converters, which serve to compute the true RMS value of an incoming AC waveform, and represent this RMS value as an equivalent DC output voltage. The outputs of these units are fed as input parameters into the ACU discussed above, which also supplies a true RMS value of a signal that may be more useful than an average rectified signal since it relates directly to the power of the input signal. 3. The final building block is the Analog Device AD734 4-Quadrant Multiplier/Divider, which serves to multiply the DC value representing RMS Voltage, with the DC value representing RMS Current, to supply the product of these two terms, which is equivalent to Output Power, since Pout = Voutlout(W, Watts). 4. The outputs of Vout, lout, Zou\, and Pout> are hence all calculated in realtime.
RF output per channel is governed by three inputs into a NAND gate (Motorola part number MC74HC10A): i. The "on time" of the pulse-width modulator for that particular channel. ii. The "on time" of the pulse-width modulator for the channel immediately proximal to the above-said channel. iii. Power Limit Set-Point that is common for all channels. This is manually set with a control knob on the instrumentation front panel.
As an example, the functional schematic of the interaction between Channel 3 input and Channel 2 output in determining Channel 3 output is shown in FIG. 7, where in the timing diagram of the Channel 3 electrode output (lower right corner) there is a slight propagation delay.
The PWM duty cycle is governed by an oscillator that is set by an oscillating frequency determined by a resistive and a capacitive component. In the present embodiment, this frequency is set at 1.7 kHz. However, if the sensitivity of the feedback-response circuit needs to be "slowed down" to increase heat build-up in the tissue, this frequency can be decreased.
FIG. 8 shows a typical ablation episode using the specific embodiment of the invention described above. Contact force is a parameter that has been measured experimentally in an in vitro setting to determine the quality of electrode-tissue contact; it has a high correlation (up to 97%) with temperature rise. Thus, when there is excellent electrode-tissue contact, there is a regular flow of RF energy transmitted into the tissue that is converted into heat energy. When this condition exists, the monitored tissue impedance and voltage is relatively constant. Therefore, the measured tissue impedance is another key parameter, because it is an indicator of electrode-tissue contact.
As described above, the information processor and RF output controller of the current invention, as well as the systems and methods of the current invention, are designed to maximize the efficacy of an ablation procedure by minimizing coagulum formation. Not to be limited by theory, these information processor and RF output controllers, systems, and methods take advantage of the following considerations.
When tissue contact is good and stable, the impedance is relatively low and constant.
As a result, less RF energy is required to reach the desired set temperature, with a shorter "ramp up" time and a lower wattage required to maintain the set temperature. The risk of coagulum formation is low because RF energy is effectively transmitted into the tissue, and heat is generated within the tissue rather than at the blood layer. Conversely, when electrode-tissue contact is intermittent, the impedance value fluctuates and the power delivered also has to adapt rapidly in order to reach or maintain set temperature. This fluctuating waveform may be conducive for coagulum formation because the rapid back and forth switching between high and low impedance causes the output power waveform to approximates the coagulation waveform used in electrosurgery.
When electrode-tissue contact is marginal or poor, impedance can rise rapidly thereby requiring more RF energy to be delivered in a fast response to achieve the same set temperature. In this last scenario, because of poor electrode-tissue contact, there is a high probability that RF energy is lost into the blood layer surrounding the electrode, thus heating the blood rather than tissue and fostering coagulum formation.
As coagulum forms on the electrode, impedance rises even more, hence bringing about a vicious cycle of climbing watts and escalating thrombus formation. Hence, one has to terminate the power delivery immediately when there is a sudden impedance rise, and the catheter should be withdrawn at this point to clean coagulum off the electrodes.
The following example describes and illustrates the methods, systems, and devices of the invention. The example is intended to be merely illustrative of the present invention, and not limiting thereof in either scope or spirit. Unless indicated otherwise, all percentages and ratios are by weight. Those skilled in the art will readily understand that variations of the materials, conditions, and processes described in these examples can be used. All references cited herein are incorporated by reference.
EXAMPLE A study was performed to analyze factors that affect coagulation formation during cardiac ablation, and to set parameters to minimize coagulation formation during this procedure. More specifically, the study was performed, at least in part, to analyze the rate of RF power delivery through ablation catheter electrodes with respect to target temperature set-points, and to determine its correspondence to coagulum formation.
This study was based on RF ablation data from 398 independent ablation episodes derived from 15 patient cases randomly picked from Phase II of the CARDIMA REVELATION™ Tx U.S. multicenter clinical trials. Patient entry criteria were symptomatic paroxysmal atrial fibrillation (PAF), refractory to at least 2 anti- arrhythmic drugs, with 3 PAF episodes within the 30 day baseline observation period. In this multicenter clinical protocol, the use of anti-coagulation agents followed these guidelines for all patients receiving RF ablation: Coumadin OK was discontinued three (3) days prior to the procedure and low molecular weight heparin was administered the day preceding the procedure. At the time of the procedure, the international normalization ratio (INR) was checked to be <1.8, and a baseline activated clotting time (ACT) value was obtained. An initial bolus of intravenous heparin was administered, and continuously administered throughout the procedure to maintain an ACT of approximately 200 to 300 seconds. The ACT measurements were taken at 30 minute intervals until therapeutic levels were achieved, then every 60 minutes for the duration of the procedure. Heparin administration was adjusted according to the ACT values.
RF ablation procedures were performed using the REVELATION Tx (CARDIMA, Fremont, CA, U.S.A.) Microcatheter. This microcatheter has eight 6 mm coil electrodes with 2 mm spacing, and eight inter-electrode thermocouples. A 9 Fr CARDIMA NAVIPORT™ steerable guiding catheter was used in conjunction with the microcatheter to aid in placement. If the target temperature was not reached, the duration to reach the maximal recorded temperature closest to the target temperature was used instead. The RFG-3E RF generator (Radionics, Burlington, MA, U.S.A.) was the RF source used for all procedures.
Software running on a computer connected to this generator was used to record the time for attaining a pre-determined target temperature, as well as the RF power and current at that time, for each RF energy application. Measurements taken included the duration time (seconds), for attaining a pre-determined temperature set- point (i.e., 50° or 55° C), and the power (watts) at that time. This was carried out for each RF energy delivery episode corresponding to each electrode. If the set- temperature was not reached, the duration to reach the maximal recorded temperature closest to the set-temperature was used instead. After each linear ablation trajectory, the catheter was withdrawn from the steerable guiding sheath, and each electrode was visually inspected. The presence or absence of coagulum was noted on clinical data sheets, thereby providing a record for analysis with the RF delivery parameters,(i.e. power, current, and duration to reach target temperature) that were logged automatically by software.
Based on the study described above, a mathematical model was used to calculate a value, the Coagulum Index, that provides insight into the likelihood of coagulum formation during an ablation procedure, and that is useful in setting parameters for an ablation procedure to minimize the potential for coagulum formation. From this model, Coagulum Index was defined:
2 Coagulum Index =(W/t)/l
Power = W (watts) Current = I (amperes)
Duration to reach Set Temperature = t (seconds)
The term on the right-hand-side of the equation, (W/t), is the slope or gradient of the power curve measured from the start of the ablation episode (baseline) to the time that the target temperature (i.e. set point temperature) or maximum temperature is first reached in an ablation episode. The derivation of the Coagulum Index, which has no physical units, is included in Appendix A.
Many dose-response relationships have been found to follow a logistic sigmoidal curve. Hence, the estimated probability of coagulum occurring, P(coag), is modeled statistically by a logistic model described by Equation 1 below, where the logit risk of coagulum is the dependant variable and the coagulum index (C.I.) is the independent or predictive variable.
e + β(C.I.)
P(coαg) ■■ 1 + eα + β(C.I.) α = -5.2932 β = 0.3803 Equation 1
Figure 9 shows the graph of this logistic model. With this model, a threshold value for coagulum index (C.I.) can be found to indicate a high probability of coagulum occurring. In a series of 398 ablation episodes from a total of 15 patient studies in the clinical studies described in this Example, it was found that the logistic model of risk of coagulum demonstrated a significant fit between Coagulum Index and the estimated percentage probability of coagulum occurring (p < 0.001 ). Table I summarizes the finding that the estimated probability of coagulum formation increases significantly when Coagulum Index increases. This analysis revealed a clear correspondence between Coagulum Index and coagulum formation. Furthermore, a distinct threshold of Coagulum Index greater than or equal to 12 was established, beyond which coagulum formation is expected. Results of this study showed that coagulum could be reduced if the slope (W/t) was gentle. This was accomplished by gradually increasing the power delivered from the RF generator, as opposed to "cranking up the watts" at the very start of an ablation episode.
C.I. 4 8 12 16 20 24
P(coag)% 2 10 32 69 91 98 FIGS. 10A and 10B show representative scattergrams of Coagulum Index values from two RF ablation patient cases. This data supports the conclusion that the derived Coagulum Index value has pertinence and value in suggesting coagulum formation. The example depicted in FIG. 10B, with Coagulum Index values less than 12, showed no coagulum formation. On the other hand, coagulum was observed in many of the energy applications of FIG. 10A, especially for those having a Coagulum Index greater than 12. For the energy applications in FIG. 10B, lower Coagulum Indexes were obtained by gradually increasing power, in contrast to an immediate increase in power levels which was used for the energy applications shown FIG. 10A. Furthermore, the maximum power setting was reduced from 50 to 30 watts in FIG. 10B.
The clinical effectiveness was analyzed for linear ablation procedures where coagulation formation was absent. During Phase I, power delivery was not controlled in a gradual manner for each ablation episode and maximum power was set at 50W. During Phase II, ablation was performed using a gradual power delivery (as described below) and maximum power was kept below 35W. As summarized in Table II, after 6 months AF episodes were reduced in Phase II patient populations. In fact, the number of patients experiencing a greater than 50% reduction in AF episodes almost doubled when using the gradual power delivery and lower maximum power for each ablation episode. A significant increase was also observed in the number of patients that no longer had any AF episodes (100% reduction), from 30% in Phase I to 53% in Phase II.
Thus, it appears that one mechanism for mitigating coagulum formation is to deliver RF power in such a way that the rise time of the power, and hence temperature curve, is more gradual and consistent. For example, when using the Radionics RFG-3E generator, with a set maximum of 30 watts, one should commence with a lower power setting of 10 watts for the about first 10 seconds, and then gradually adjust the knob on the RF generator to the set maximum of 30 watts, while still maintaining total RF delivery time at 60 seconds. When this technique was applied, it decreased coagulum formation, as is evident by the data shown in FIG. 10. Specific characteristics of RF generators must be considered to obtain the gradual power rise described above. The IBI-1500T has 4 user-selectable choices for controlling the power delivery ramp-up curve. The Osypka 300 Smart and Cordis Webster Stockert have built-in algorithms which appear to automatically regulate power delivery rise time in a gradual manner, the latter allowing the end-user to specify a temperature ramp-up time. And finally, the Medtronic Atakr has no user override controls for power delivery application. In comparison, the Radionics RFG-3E allows the user to manually increase power output during the delivery of RF energy. In the present embodiment of this invention, the output power setting for RF energy to be delivered at the electrodes are user adjustable via the front panel knob (1-30 Watt). A lower power setting will increase the ramping time, since it takes a longer time to reach set temperature. An automatic algorithm which calculates the coagulum index (C.I.) in real-time can be incorporated into the information processor and RF output controller functionality so that a visual or auditory signal can alert the end-user whenever the risk for coagulum formation is high, i.e. C.I. greater or equal to 12. Alternatively, the information processor can calculate the C.I. in real-time and use this calculated value as information that is fed back to the RF output controller functionality so that the ablation episode can be carried out with minimal probability of coagulum formation.
Excellent electrode-tissue contact is determined by a combination of fluoroscopy, low initial impedance, and the quality of electrograms during the procedure. Results from the study reveal that excellent electrode-tissue contact, in combination with gradual RF power delivery to a maximum level of 30 to 35 watts, constitutes a sound prescription for best practice of RF ablation with the least likelihood of coagulum formation at the electrode site. Bench testing of tissue ablation has also demonstrated that good electrode contact with the tissue results in lower RF power consumption required to reach set temperature. Lower RF energy requirements in turn reduce the probability of coagulum formation. The insights revealed in this example may be extrapolated to procedures using other catheters for other RF ablation procedures as well, and hence are presented here. The catheter MAZE procedure calls for the creation of linear 'barricades' along anatomical trajectories within the right atrium, using RF ablation to compartmentalize the chamber and 'contain' pro-arrhythmic electrical propagation. Results of this study reveal the following considerations regarding minimizing coagulum formation during cardiac tissue ablation. In ideal situations, it is possible to achieve satisfactory tissue contact for all eight linear ablation catheter electrodes. However, the techniques discussed below yield acceptable results in right atrial MAZE linear ablation procedures even when the anatomical or flow conditions prevent optimal simultaneous contact of eight catheter electrodes. a) Excellent contact should be established in as many linear array electrodes as possible. b) Low tissue impedance at 'baseline' is indicative of effective contact; some RF generators permit this to be sensed and displayed prior to actual ablation by emitting a small RF current to interrogate tissue impedance at the ablation site. c) Pacing threshold, if used as an indicator of contact, should be reasonable (1-2 mA); threshold values above 4-5 mA most likely indicate poor contact, and the catheter should be repositioned. d) The sheath should be rinsed periodically (e.g. every 15 minutes) with a standard heparinized saline solution bolus. This improves contact by removing coagulum build-up on the electrodes and catheter shaft. If possible, the catheter should be pulled out of the Naviport deflectable guiding sheath after each trajectory; the electrodes should be wiped clean if needed, before re-introducing the catheter into the Naviport. In addition to achieving excellent electrode-tissue contact, reduced coagulum formation can be obtained by regulating the RF power settings such that power is gradually increased and by setting the generator maximum power settings to 30W - 35W with power monitored continuously. The catheter should be repositioned as needed to maintain set temperature at a lower power level. It has been observed that coagulum formation is more evident when power required to maintain set temperature approaches 50 W. Conversely, coagulum formation is minimized greatly when power required is less than 35 W. This may be seen as a challenge when trying to reach set temperature. However, with excellent electrode-tissue contact, desired set temperature can be achieved with as low as 7 W to 15 W of power delivery. In vivo animal studies have verified deep, transmural lesions with these low power settings when there is sufficient electrode-tissue contact.
While there has been illustrated and described a preferred embodiment of the present invention, it will be appreciated that modifications may occur to those skilled in the art, and it is intended in the appended claims to cover all those changes and modifications which fall within the true spirit and scope of the present invention.
Mathematical Derivation of Coagulum Index, using Dimensional Analysis of Physical Parameters
Pertinent to RF Ablation
A mathematical model for distinguishing between coagulum or non- coagulum formation on the RF-ablating electrode of the Cardima REVELATION Tx catheter was developed. This model was based on dimensional analysis of physical constants pertaining to the units for various logged parameters during RF ablation episodes, and was verified using clinical data obtained as described in the Example section.
Definitions in S. I. (System International) Units: Mass = Kg [kilogram]
Length = m [meter]
Time = s [seconds]
2 -3 Power = W [watts] = Kg * m * s
Each single-electrode catheter ablation event has its own slope calculated from a plot of Power (Y-axis) vs. Time (X-axis), from baseline temperature
(i.e., temperature of free-flowing blood in the heart = approximately 37°C.) to 50° C.
In this analysis, this is the duration for the sensed temperature from a thermocouple to reach a set temperature, e.g., 50° C. If the set temperature cannot be reached, then it is the duration for the sensed temperature to reach the maximum temperature, for that ablation episode.
Slope = Power/Time
= (Work Done/Time) / Time
2 = (Force * Displacement) / Time
= (Mass * acceleration * Displacement) / Time Eqn.
Dimensional Analysis of the units show that:
Slope = Kg * m * s * m / s
2 -4 = Kg * m * s Eqn.
It follows that 1/Slope is the reciprocal of Eqn. :
1/Slope = Kg"1 * m"2 * s4 Eqn.
Now we define electrical capacitance, C, in terms of its fundamental units: -2 -1 4 2 C = m * Kg * s * l [NIST]
-1 -2 4 2 Rearranging terms, C = Kg * m * s * l Eqn.
Dividing both sides by I2: C / 12 = Kg"1 * m"2 * s4 = t/W Eqn. Notice that Eqn.  = Eqn. 
Therefore, we can define capacitance as a function of the slope that we obtain for each ablation episode:
C = l * (t/W) = I2 / (W/t) = I2 / Slope Eqn.  In the presence of an alternating current, impedance Z is defined as: Z = 1/(2πfC) Eqn. where f = operational RF frequency
Substituting Eqn.  into Eqn. , we are able to define Coagulum Index as follows:
Relative Impedance = k * (W/t)/ 1 Eqn.  where k = 1/(2πf), and is constant for a particular RF generator, assuming that the RF oscillator frequency, f, is stable and constant. Therefore, for practical purposes, the proportionality constant k is ignored in the calculation since the same type of RF generator, the Radionics RFG-3E, was used throughout the study described in the Examples section. The results discussed in the Examples section showed a close correspondence between this calculated value and the probability of coagulum formation at the ablation electrode site. Therefore, the term Coagulum Index was given to this quantity. We therefore arrive at: Coagulum Index = (W/t)/l2
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|International Classification||A61B18/14, A61B18/12|
|Cooperative Classification||A61B2018/00357, A61B2018/00678, A61B2018/1253, A61B2018/00648, A61B2018/00827, A61B2018/1467, A61B2018/00702, A61B18/1206, A61B2018/00875, A61B2018/00791, A61B18/1492, A61B2018/00797, A61B2018/00892, A61B2018/0016|
|European Classification||A61B18/14V, A61B18/12G|
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