The present invention relates to electrophysiological catheter systems, for example for use in the treatment of atrial fibrillation. It has particular application in the location and ablation of sources of atrial fibrillation.
Atrial fibrillation (AF) is the most common cardiac arrhythmia experienced worldwide. The condition affects primarily people over the age of 50 and therefore its prevalence is expected to increase in the future due to the rising trends in average age of populations. Pulmonary Vein Isolation (PVI) is an alternative to pharmaceuticals as a treatment for the condition, with a current 50-70% success rate. PVI involves the ablation of tissue around all four pulmonary veins to isolate the left atrium from known external AF inducing electrical activity.
Ganglionated Plexi (GP) sites are regions of the autonomic nervous system inside the left atrium where AF-type events have been shown to originate from. These sites are not specifically targeted by PVI. Experimental GP-based treatment has been performed which involves ablation only at the active GP sites with the aim of eliminating the AF inducing pathways inside the left atrium. Preliminary results from human trials indicate that this method can be as effective as PVI whilst using much lower ablation energy; damaging lower volumes of tissue.
GP sites involved in AF can only be identified using specific electrical stimuli to induce AF-related events, as the number and location of the active sites is patient-dependent. There is no equipment currently available dedicated to performing GP stimulation, which results in the process of identifying and classifying the GP sites being laborious, inconsistent and time consuming.
A direct consequence of the unique stimuli used for cardiac applications, including GP identification, is the deterioration of recorded signals due to stimulus artefacts; especially when recording from electrodes located near the stimulation sites. This effect results from the high amplitude stimuli, required to affect the autonomic nervous system, completely saturating any recording instrumentation sensitive enough to pick up the local tissue response.
The present invention provides apparatus for electrophysiological studies, the apparatus comprising a stimulation channel, a plurality of detection channels, and control means. The control means may be arranged to provide a stimulation signal to the stimulation channel and to process detection signals from the detection channels thereby to identify ectopy events in the detection signals.
The apparatus may further comprise one or more further stimulation channels, and the control means may be arranged to provide a further stimulation signal for each of the further stimulation channels.
The control means may be further arranged to identify ventricular activation events in the detection signals.
The control means may be arranged to control the stimulation signal in response to the outcome of the processing of the detection signals. For example the control means may be arranged to stop producing the stimulation signal in response to detection of a predetermined number of ectopy events. The predetermined number may be one.
The detection channels may include an atrial channel and at least one reference channel. The control means may be arranged to process the detection signal from the at least one reference channel to identify ventricular activation events. The control means may be arranged thereby to distinguish between ventricular activation events and ectopy events in the detection signal from the atrial channel.
The detection channels may include a plurality of atrial channels. The control means may be arranged to process a detection signal from each of the atrial channels. The control means may be arranged to identify an event as an ectopy event only if it is detected in the detection signal from each of the atrial channels.
The control means may be arranged to determine the timing of an ectopy event on each of said plurality of atrial channels. The control means may be arranged, from the timings, to locate the source of the ectopy event.
The apparatus may further comprise an atrial catheter. The atrial channel may be connected to at least one electrode on the atrial catheter. The apparatus may further comprise a ventricular catheter. One of the at least one reference channels may be connected to at least one electrode on the ventricular catheter. The apparatus may further comprise an ECG electrode set. One of the at least one reference channels may be connected to the ECG electrode set.
The at least one output channel may include a pacing channel. The pacing channel may be the stimulation channel or it may be a separate channel. The control means may be arranged to provide a pacing signal to the pacing channel.
The control means may be arranged to identify ventricular activation events that are caused by the pacing signal. The control means may be arranged to modify or stop the pacing signal in response to the identification of a predetermined number of ventricular activation events that are identified as caused by the pacing signal.
The control means may be arranged to operate in a ventricular activation test mode, or to perform a ventricular activation test, in which the pacing signal is output without the stimulation signal. The number of ventricular activations detected during the test may be compared with a threshold number to determine whether the test is passed or failed. If the test is passed the control means may enable the stimulation signal. If the test is failed, the stimulation signal may be inhibited. For example a user interface may only enable a user to start the stimulation signal if the test has been passed.
The control means may be arranged to identify ventricular events. The control means may be arranged to measure a delay between consecutive ventricular events. The control means may be arranged to determine whether the delay exceeds a predetermined time period. The control means may be arranged to determine, from the delay, the presence of one or more atrioventricular node slowing GPs.
The stimulation signal may comprise a plurality of stimulation pulses, which may be arranged in groups or may be output in a continuous sequence, for example at a constant frequency.
The pacing signal may comprise a pacing pulse. The pacing pulse may precede each of said groups of stimulation pulses.
The control means may be operable in an ectopy triggering mode in which the system is arranged to produce the pacing pulses and the groups of stimulation pulses, and an atrioventricular node slowing mode in which the system is arranged to produce the stimulation pulses without the pacing pulses.
The control means may comprise a user interface arranged to enable a user to select one of the modes and to adjust at least one parameter of the stimulation signal or the pacing signal.
Each of the stimulation pulses may be a bipolar voltage pulse.
The control means may be arranged to define a target current and to control the stimulation signal, during each of the stimulation pulses, or between the stimulation pulses, to achieve the target current.
The stimulation signal may be applied across two stimulation electrodes. For example it may be applied as a voltage difference between the two electrodes. The control means may be arranged to control the impedance between the stimulation electrodes between the stimulation pulses thereby to control an offset voltage between the electrodes. For example the control means may be arranged to reduce the impedance between the electrodes for the periods between the stimulation pulses.
The apparatus may further comprise artefact reduction means arranged to reduce the effect of the pacing signal on the detection signal. The artefact reduction means may comprise at least one analogue component, and/or it may comprise digital signal processing means.
The invention further provides apparatus for electrophysiological studies, the apparatus comprising: a stimulator output channel; a plurality of detection channels; and control means arranged to provide a stimulation signal to the output channel and to process detection signals from the detection channels, wherein at least one of the recording channels comprises a hardware tunable notch filter. The control means may be arranged to generate the stimulation signal at one of a plurality of stimulation frequencies and to tune the notch filter to filter out components of the detection signal of the at least one detection channel at said one of the stimulation frequencies.
The notch filter may be arranged to filter out components of the detection signal of the at least one recording channel at at least one harmonic of said one of the stimulation frequencies. This may be useful for example for detectors which are close to a stimulation electrode of the system.
At least one of the detection channels may not include a hardware tunable notch filter. This may be suitable for a detector which is remote from the stimulation electrode.
The control means may be arranged to select said one of the stimulation frequencies in response to a user input.
Referring to
The atrial probe 106 has a number of electrodes 116 spaced along its length. One of these 116a may be a stimulation electrode, or pair of electrodes, and the others 116b, 116c, 116d may be detection electrodes, or detection electrode pairs. The arrangement of the electrodes will depend on a number of factors, including whether unipolar or bipolar signals are used. If the system is operating in unipolar mode, a reference electrode will also be provided as a patch on the surface of the body and the voltage on each of the electrodes 116a-116d on the probe is measured relative to the voltage of the reference electrode. If the system is operating in bipolar mode, then the voltage difference between the two electrodes in each pair is measured.
Referring to
Each of the detection channels of one of the groups 208 of bipolar detection channels may comprise a subtraction unit 230, such as a comparator, having two inputs 232, 234 each connected to a respective one of the two input terminals 236, 238 of the channel, and an output in the form of a difference signal that varies with the difference between the signals on the two input terminals 236, 238. The channel may further comprise a band pass filter 240 connected to the output of the subtraction unit 230, and arranged to filter the difference signal so as to pass only components of that signal within frequency band. For example the filter may pass signals with frequencies in the range from 30 to 250 Hz. The output of the band pass filter 240 may be connected to the input of an amplifier 242 which is arranged to amplify the filtered difference signal. The output of the amplifier 242 is connected to the ADC 214 which is arranged to digitize the amplified filtered difference signal and input it to the data controller 202. These channels are suitable for detection signals that will not include significant interference from the stimulation pulse. Examples may include electrodes on the ventricular probe 108 or the ECG electrode set, and electrodes on the atrial probe 106 which are remote from the stimulation electrodes 116a.
Each of the detection channels of another one of the groups 210 of bipolar detection channels may include all of the components of the first group 208, which will not be described again and are indicated by the same reference numerals, but may also comprise one or more notch filters 241 each of which is arranged to filter out components of the detection signals in a narrow band about a predetermined frequency. The notch filter frequencies may be set to the frequency of the stimulation signal and/or one or more harmonics of the frequency of the stimulation signal as will be described in more detail below. The notch filters 241 also may be tunable so that they can be adjusted to match the stimulation signal if the frequency of the stimulation signal is varied. The notch filters 241 may be arranged between the subtraction unit 230 and the amplifier 242, for example connected between the output of the band pass filter 240 and the input of the amplifier 242. These channels are suitable for detection signals that will include significant interference from the stimulation pulse. Examples may include electrodes on the atrial probe 106 close to the stimulation electrodes 116a. However it will be appreciated that the notch filters may be included for all detection signals.
Each of the unipolar detection channels 212 may comprise a subtraction unit 250, such as a comparator, having two inputs 252, 254 one of which 252 is connected to the unipolar input terminal 256 of the channel and the other of which 254 is connected to a reference voltage 258, such as a reference electrode on the body surface or an intra-cardiac reference electrode. The subtraction unit 250 may therefore produce an output in the form of a unipolar difference signal that varies with the difference between the signal on the input terminal 256 and the reference voltage 258. The channel may further comprise filter components, such as a high pass filter 260 and a low pass filter 261 connected in series to the output of the subtraction unit 250, and arranged to filter the unipolar difference signal so as to pass only components of that signal within a frequency band between the cut-off frequency of the high pass filter 260 and the cut-off frequency of the low pass filter 261. For example the low pass filter 261 may pass signals with frequencies above 250 Hz and the low pass filter may be tunable have a variable cut-off frequency. The output of the low pass filter 261 may be connected to the input of an amplifier 262 which is arranged to amplify the filtered unipolar difference signal. The output of the amplifier 262 may be connected to the ADC 216 which is arranged to digitize the amplified filtered difference signal and input it to the data controller 202.
Each of the detection channels 208, 210, 212 may comprise an output connected to the respective channel, for example between the filters in the channel and the amplifier in the channel, which is arranged for connection to an external recorder. This allows the filtered detection signals, for example the pre-gain detection signals as shown in
The processing unit 114 may further comprise a bipolar power supply module 270 arranged for connection to a DC power supply. The power supply module 270 may be arranged to output positive or negative voltage power signals at a number of different voltages. The power supply module 270 is connected to the stimulation channel 206 so that the stimulation signals can be varied between maximum positive and negative voltages, producing a bipolar stimulation signal.
The computer 102 is connected to the data controller 202, for example by a USB interface, and may also provide power to the data controller 202. The computer 102 is arranged to run software that enables it to act as a graphical or other user interface for the system. For example the software may enable a user to set various parameters of the system as will be described in more detail below.
In operation, a user can set appropriate parameters of the stimulation signal, such as peak voltage or current, pulse length and pulse frequency, via the user interface 100, which is then arranged to communicate those parameters to the control system 104. The data controller 202 is arranged to generate from the parameters a digital stimulation signal which it then transmits to the stimulation channel 206 where it is converted to an analogue stimulation signal which is output via the stimulation terminals 224, 226 of the processing unit 114, and via the mapping system 112, to two of the electrodes on the atrial probe 106, or a dedicated stimulation probe if appropriate. The stimulation signal maybe arranged, for example, to stimulate activity in the heart, such as by stimulating any ganglionated plexi. The resulting activity, or indeed any activity, in the heart, can generate electrical signals in each of the probes 106, 108 and the ECG electrode set 110, which are input, via the mapping system 112, to the terminals of the detection channels 208, 210, 212. Depending on the requirements for a particular operation, the detection signals from the atrial probe 106, the detection signals from the ventricular probe 118, and/or the detection signals from the ECG electrode set 110 are input on one or more of the detection channels 208, 210, 212, where they are filtered, amplified and digitized, before being transmitted to the computer 102. The computer 102, using appropriate software, is arranged analyse the digital detection signals to determine the location of any GP sites detected, and provide feedback or analysis to the user as appropriate. For example the system may be arranged to build up a map of the GP locations in the left atrium as the atrial probe is moved around the atrium, so that the map can be used subsequently to guide ablation. Alternatively, or in addition, the location of a detected GP site can be determined within a few seconds, and so ablation of each detected site may be carried out when it is detected.
It will be appreciated that the system of
The system may be arranged to provide autonomic stimulation. For example in one mode the system may be arranged, when the patient is in sinus rhythm, to detect ganglionated plexi that trigger ectopy. In another mode the system may be arranged, when the patient is in atrial fibrillation, to detect ganglionated plexi that slow the atrioventricular node.
In one mode of operation the system may be arranged to produce high frequency stimulation pulses to stimulate ectopy-triggering GPs, and to analyse the detection signals received on one or more of the detectors to detect the presence of a GP and/or determine the location of each GP. Referring to
The pacing pulse 300 will produce a corresponding pulse 300a in the detection signal on each of the detection channels, which will in general appear as a biphasic pulse, even for monophasic stimulation pulses, as a result of the filtering in the detection channels. It should also be noted that as the output of the stimulator is galvanically isolated from the detector, the reference potentials on the channels may not be at the same voltage. The magnitude of the detected pacing pulse 300a will depend on the location of the electrode at which it is generated, but provided it can be detected on each of the channels it can be used in the analysis of the detection signals. Similarly the stimulation pulse group 302 will produce a corresponding biphasic pulse group 302a on each of the detection channels. These pulses 300a, 302a will generally be weaker in the detection signals from the ECG electrodes 110 or ventricular probe 118. For any detection signals that are received on one of the channels 210 including notch filters 241, those notch filters 241 will of course filter out the stimulation pulse group 302a from the detection signal. In order to achieve that, as discussed above, the notch filters are adjusted to filter out the fundamental frequency of the stimulation pulse group 302 and at one or more harmonics of that fundamental frequency. For example the first three or four harmonics may be filtered out separately by the adjustable notch filters.
In response to the stimulation pulse 302, atrial ectopic events may be triggered. These can be detected and used to detect and locate ectopy-triggering GPs. Also ventricular events may be triggered. These need to be distinguished from atrial ectopic events. Atrial ectopic events will produce a pulse 304a in each atrial detection signal, i.e. the detection signals from the detection electrodes on the atrial probe 104, and also a pulse 304b in the ventricular detection signal, i.e. the detection signal from the ventricular probe 108, and the ECG detection signal, i.e. the detection signal from the ECG electrodes. This atrial ectopic pulse will be relatively strong in the atrial detection signals and relatively weak in the ECG and ventricular detection signals. Ventricular events will also be detected, but these will appear as a relatively strong ventricular pulse 306b in the ventricular detection signal and a relatively weak pulse 306a in the atrial detection signals.
In order to detect and classify the various pulses in each of the detection signals, the signal is processed using an algorithm which is part of the software running on the computer 102. Firstly, in order to identify potentially relevant events, each signal is put through a Canny edge detector, and then rectified and filtered. The result is as shown by the broken line for the first atrial detection signal in
Referring to
In order to identify ventricular events, the surface ECG signals, or a ventricular catheter placed directly inside the ventricle, can be used to detect ventricular events. Various methods of doing this are known in the art. When a ventricular event is detected in the ECG or ventricular detection signals, any events detected on the atrial channels that coincide with the ventricular event, to within a predetermined time period, are treated as related to ventricular activation and are discarded from further analysis. For example there may be a ‘blanking period’ of 50 ms either side of each ventricular event during which any events in the atrial detection signals are omitted from further analysis. Therefore, if the event in the atrial detection signal is within a predetermined time period of the ventricular event then it is identified as a ventricular event, and the process returns to step 400 to identify another event.
Any event identified in the atrial detection signals, which is not identified as being due to pacing or HFS stimulus artefact, or due to ventricular artefact, is identified as indicative of a true atrial activation and classified as an atrial activation event. In order to reduce the chances of error, if an atrial ectopic is detected then at step 408 the detection algorithm compares the timing of the detected activation in other atrial recordings (A1, A2, . . . , An). An atrial ectopic event will only be registered if present in all, or at least a predetermined number, of the atrial detection signals. This provides additional capability to accurately assess ectopy in the presence of measurement noise.
Once a true atrial ectopic event has been identified, then at step 410, the timings of the event in the different atrial detection signals, together with the locations of the catheter electrodes from which those signals are obtained, are used to determine the position of the source of the atrial ectopic event. Essentially this is done by assuming a constant speed of propagation of activation from the source to the electrodes, and therefore using the timings of the event in the different atrial detection signals to estimate the distance of the source from all of the electrodes. Once the location of the source has been determined, that location is recorded at step 412 on the 3D model of the heart which is stored in the mapping system 112. This can subsequently be used to locate the GP for ablation.
It will of course be appreciated that the various steps in the process of
When the detectors 106, 108, 110 are in place, the timing and stimulation pulses are transmitted at an appropriate frequency and the detection signals analysed immediately. This allows the stimulation signal to be controlled and modified in response to the detected events, as will now be described.
The process of
Firstly, prior to any attempt at autonomic stimulation, the system may operate in a test mode in which slow (safe) high output pacing pulses may be generated and transmitted on the stimulation channel, without any additional stimulation pulses, for a predetermined period of time, in order to make sure that the ventricle is not within range of the pacing catheter. If a predetermined number of ventricular activation events, which may just be one event, are detected by the software algorithms, using the ECG or ventricular detection signals as described above, then the user is alerted via the user interface 100 and autonomic stimulation is temporarily disabled. If no ventricular events are detected then. The operation of the user interface 100 is described in more detail below.
If no (or less than the predetermined number of) ventricular events are detected in response to the pacing pulses during the test period, then the user interface 100 may be arranged to indicate this to the user, and the software enables the user to select and start one of the detection modes, such as one of the GP detection modes described above, during which the stimulation signal with stimulation pulses with or without the pacing pulses may be started. During the period when the atrium is activating, a short burst or group 302 of high-frequency stimulation pulses 303 are generated to attempt ganglionated plexus stimulation. If a premature atrial ectopic 304a is detected, then this is a positive response. The positive response is automatically detected by the signal processing algorithm as described above. Further high frequency stimulation may then be stopped to avoid additional risk of inducing atrial fibrillation, and the user may be alerted to the result via the graphical user interface 100. The user may then move the atrial probe 106 and re-start the pacing pulses to check again for stimulated ventricular activation. If no stimulated ventricular activation is detected in response to the stimulation pulse 302, the high frequency stimulation pulse may be repeated, and the repeating pulses may be continued until a further atrial activation event is detected. If the stimulation signal has been output for a predetermined period, or a predetermined number of pulse groups, without detection of an atrial activation event, then the control software may be arranged to temporarily disable or stop it so as to avoid excessive stimulation which may result in AF, and again this may be indicated to the user via the user interface 100.
When a patient is in atrial fibrillation (AF) the system may be arranged to detect and locate atrioventricular node slowing ganglionated plexus (AVN-GP). In this mode, which again may only be selected via the user interface 100 if the test mode has not detected any ventricular events, if the patient is in atrial fibrillation then a continuous burst of high frequency pulses 303 without pacing pulses 300, is delivered on the stimulation channel 206. If there is an AVN-GP site, then this causes autonomic effects on the atrioventricular node and this, in turn, causes heart rate slowing, which can often result in a long pause in ventricular activation. The software algorithm is therefore arranged in this mode to analyse the detection signals to identify ventricular activation events, as described above, and to analyse the timings of those events. If a pause of at least a predetermined time period, or delay, between consecutive ventricular activation events is detected, which may for example be 2 s or 3 s, then this is taken as indicative of the presence of AVN-GP. In response to the detection of such a pause, the autonomic stimulation signal is stopped and the user is alerted via the computer 102.
Referring to
Referring to
Referring to
Referring to
Referring to
The autonomic stimulation options may be made available to a user of the system only on certain conditions. For example the conventional modes of operation mentioned above with reference to
Cardiac stimulation as described above can cause disruptive artefact on the recording of intracardiac electrical signals. This is made worse in the presence of filtering that is intended to remove noise. The filters take time to settle and have transient properties that are not favourable in the presence of a non-physiological high amplitude pacing signal.
This circuit is arranged to operate in two modes
a) As a normal amplifier with gain 1-100× when its input voltage |Vin|<Vth
b) As a voltage clamp at a pre-determined level Vc when |Vin|>Vth where Vc=Vth*Amplifier Gain. The threshold voltage Vth may be set to a level well above the amplitude of intra-cardiac signals and hence would be exceeded only during stimulation. The input signal should be AC-coupled or bipolar to prevent undesired clamping from excessive DC-offset drift.
An analogue filter that operates in two modes
a) Normal filter when |Vin|<Vth
b) Voltage clamp at a pre-determined level Vc when |Vin|>Vth
Such a filter would retain all relevant filter characteristics during normal recordings but make use of internal diodes to improve the transient characteristics immediately after stimulation. Vth characteristics would be identical to the voltage limiter circuit. A suitable circuit is described in Texas Instruments (2019). Fast-settling low-pass filter circuit. Analog Engineer's Circuit: Amplifiers. SBOA244—January 2019 http://www.tij.co.jp/jp/lit/an/sboa244/sboa244.pdf
A gain-stage that operates in two modes:
a) High-gain: Gain ranging from 1-100×
b) Low-gain: Gain ranging from 0.001-1×
High-gain mode may be used when recording normally for optimal signal-to-noise performance. Low-gain mode would be employed only during stimulation to prevent amplifier saturation and improve transient performance; by limiting the amplitude of all fast transitions induced by stimuli.
The analogue inputs may be disconnected during stimulation using an analogue switch. They may be left floating or connected to a fixed external potential.
The analogue inputs may be connected to a sample and hold circuit. The input will be tracked during normal recording and held at the pre-stimulation potential during stimulation.
Use the artefact-affected output of a recording channel synthesize a digital “artefact estimation” signal containing only the observed artefact. Generate the analogue artefact estimation signal via means of a digital to analogue converter. Subtract, in analogue using a differential amplifier, the artefact estimation signal from subsequent inputs to the recording channel during stimulation.
Set all data acquired during stimulus output to 0 amplitude.
Set all data acquired during stimulus output to the last acquired sample amplitude before stimulation. Alternatively use an average amplitude from a set of the last acquired pre-stimulation samples.
Set all data acquired during stimulus output to a value interpolated using the last acquired pre-stimulation sample and the first acquired post-stimulation sample. Alternatively use an average amplitude from a set of the last acquired pre-stimulation samples/first acquired post-stimulation samples.
Low-pass filter to attenuate high-frequency components of stimulation artefact, and high-pass filter to attenuate any residual DC offsets, with cut-off frequencies of both optionally being tuned during stimulation to improve artefact suppression performance at the expense of recorded bandwidth. Wideband analogue filtering (DC of frequencies between 0.05 Hz to Fsampling/2 where Fsampling is the digital sampling frequency of the analogue signal) may be employed to enable maximal manipulation of the signal bandwidth.
Record simultaneously from the same electrode with two channels; one which does and one which does not employ any of the analogue or digital methods described. Alter parameters of the artefact reduction method employed using the similarity between the two recorded signals.
For example when blanking:
If the two channels both appear saturated immediately after stimulation, increase the blanking interval to improve settling time on the artefact reduction channel.
Referring to
Referring to
Referring to
In both of these simulations it can be seen that the ectopic and ventricular pulses are clearly extracted so that the analysis such as that described above with reference to
Number | Date | Country | Kind |
---|---|---|---|
1911731.6 | Aug 2019 | GB | national |
Filing Document | Filing Date | Country | Kind |
---|---|---|---|
PCT/GB2020/051951 | 8/14/2020 | WO |