Catheter and method for detecting synergy disorder caused by synchronization disorder

Abstract

The present invention provides a catheter for assessing cardiac function, the catheter comprising an elongate shaft extending from a proximal end to a distal end, where the shaft comprises a lumen for guidewire and / or saline irrigation. The catheter further comprises: at least one electrode disposed on the shaft for sensing an electrical signal in a bipolar or monopolar manner and applying pacing to a patient's heart; at least one sensor disposed on the shaft for detecting an event related to a rapid increase in the rate of pressure increase in the left ventricle of the patient; and a communication device configured to transmit data received from the electrode and the sensor.

Description

Technical Field

[0001] The present invention relates to a catheter, and in particular to a catheter that can be utilized in systems and methods for detecting dyssynergy due to dyssynchrony, systems and methods for determining the optimal number and location of electrodes for cardiac resynchronization therapy, and / or methods and systems for measuring fusion time as a means of determining the degree of concurrent activation of the heart. Thus, the present invention can be used in patients with dyssynchronous heart failure, and more particularly, can be used to identify patients who may respond to resynchronization therapy, and optionally determine the optimal location for placing electrodes to stimulate the heart. The present invention can also be used in patients with dyssynchronous heart failure. Background Art

[0002] Cardiac resynchronization therapy (CRT) is always provided according to recognized medical standards and guidelines provided by international medical societies to treat patients with various conditions such as widened QRS complexes, bundle branch block (left or right), and heart failure. There are some minor differences between medical guidelines regarding the specific conditions that should occur before using CRT, such as how wide the QRS complex is, what type of bundle branch block is present, and the degree of heart failure.

[0003] CRT is associated with reduced mortality and morbidity; however, not all patients benefit from this treatment. In fact, some patients may experience disease progression after treatment, some develop devastating complications, and some experience both.

[0004] In this regard, it would be beneficial to provide a unified strategy that could reduce the number of non-responders to CRT and optimize the treatment of potential responders and thus improve the effectiveness of therapy.

[0005] One method of identifying such responders may be to detect the onset of synergy after pacing and determine the patient's resynchronization potential. For example, such methods for determining the onset of synergy are defined in GB1906064.9, PCT / EP2020 / 062149, and national phases resulting therefrom. The proposed treatment may be suggested by determining the potential optimal number and position of electrodes (e.g., by taking measurements to determine the extent of parallel activation). For example, such methods for determining the extent of parallel activation are described in GB1906055.7, PCT / EP2020 / 062146, and national phases resulting therefrom. For a given treatment, the effect may be verified by calculating the fusion time of the wavefronts of the wavefronts, thereby giving an indication of the extent of parallel activation of the heart. For example, such methods for determining the fusion time of the heart are described in GB1906054.0, PCT / EP2020 / 062152, and national phases resulting therefrom. General catheters for performing any such methods and further discussion of these methods are disclosed in GB2016234.3 and PCT / EP2021 / 078365.

[0006] However, it would be desirable to provide a catheter that is better suited for carrying out the above method.Such a catheter may additionally be provided with a data processing module that may additionally process data received from the catheter to provide a measure of any of the above values ​​without requiring further post-processing of the data. Summary of the invention

[0007] Viewed from a first aspect, the present invention provides a catheter for assessing cardiac function, the catheter comprising

[0008] An elongated shaft extending from a proximal end to a distal end, the shaft having a first curve, a second curve, a third curve, and a fourth curve, the shaft comprising:

[0009] a lumen, which is used for guidewire and / or saline flushing;

[0010] at least one first electrode disposed on the second curve of the axis and configured to contact the septum of the left ventricle of the patient in use, the at least one first electrode being used to sense electrical signals and apply pacing to the patient's heart;

[0011] at least one second electrode disposed on a third curve of the shaft and configured to contact, in use, a free wall of a left ventricle of the patient, the at least one second electrode being used to sense electrical signals and apply pacing to the patient's heart, the third curve of the shaft having a larger diameter than the second curve of the shaft;

[0012] at least one sensor disposed on the shaft for detecting an event associated with a rapid increase in the rate of increase of pressure within the patient's left ventricle; and

[0013] A communication device is configured to transmit data received from the electrodes and sensors.

[0014] As discussed below, such a catheter can provide specific uses in determining the function of the heart, and in particular in providing a measure indicating whether there is dyssynergy caused by desynchronized electrical activation in a patient. When the catheter is properly positioned in the left heart chamber while the electrodes are opposite each other at the septum and the contralateral wall and the sensor is in the chamber, with each heart beat, the voltage gradient between each electrode and the reference electrode is recorded. Such a voltage gradient represents the electrical activation of the heart at the electrode site. The time course of activation of the different electrodes determines the degree of desynchronization. In addition, and in accordance with the above, the sensor records events related to the onset of synergy, that is, events related to the rapid increase in the rate of pressure rise in the left ventricle, which reflects the point at which all segments of the heart begin to stiffen actively or passively. The time of the event is compared with the degree of electrical activation and desynchronization, and the presence of dyssynergy caused by desynchronization is recorded. Although the rapid increase in left ventricular pressure is mentioned herein, it will be understood by those skilled in the art that such an event can be more generally manifested as pressure in the patient's heart. In this way, the catheter does not have to be placed in the patient's left ventricle.

[0015] The heart can then be stimulated from one or more electrodes. With each heart beat, a voltage gradient is recorded between each electrode and a reference electrode, which voltage gradient, as described above, can represent electrical activation of the heart. One or more sensors again record events associated with the onset of synergy. The new set of time events can then be compared to the first set of events, and the presence or absence of synergy caused by resynchronization is recorded.

[0016] Advantageously, using such a system, such measurements for various locations of electrodes can be determined quickly and efficiently. In this way, not only can it be determined whether a patient is indeed a possible responder to cardiac resynchronization therapy, but the ideal number and location of electrodes can also be quickly determined.

[0017] The at least one sensor includes a pressure sensor, a piezoelectric sensor, a fiber optic sensor, and / or an accelerometer. Such sensors can be used to detect events associated with a rapid increase in the rate of increase of pressure in the left ventricle, as discussed further below.

[0018] The stiffness of the elongated shaft can vary along its length between the proximal end and the distal end. In this way, the elongated shaft can have a structure that is ideal for safe, quick and easy positioning within the patient's heart. Optionally, the elongated shaft is provided with a rigid proximal end, a middle portion of moderate stiffness, and a flexible tip at the distal end. Again, such a structure provides a catheter that can be safely and easily manipulated within the heart.

[0019] To provide this varying stiffness along its length, the elongated shaft may include a multi-lumen extrusion having a first cap around the proximal end, a second cap around the middle portion, and a third cap around the distal end, the first, second, and third caps having different stiffnesses. In this way, the elongated shaft may include a single extrusion of a single material extending along the entire length of the shaft, and the stiffness of the extrusion may vary along its length depending on the stiffness of the caps provided at certain points around the extrusion. The multi-lumen extrusion may include Pebax 63D, the first cap may include Nylon 11 or 12 and optionally braided wire, the second cap may include Pebax 35D, and the third cap may include Pebax 75D or Pebax 55D. Such a shaft may be easier to manufacture than a shaft whose composition varies throughout.

[0020] The first curve may be a counterclockwise curve having a first diameter, the second curve may be a clockwise curve having a second diameter, the third curve may be a clockwise curve having a third diameter, and the fourth curve may be a clockwise curve having a fourth diameter. The curves are described herein as clockwise and counterclockwise in order to clearly distinguish the directions of the curves, it being understood that these directions may be reversed. For example, if the catheter is flipped, a curve that was previously clockwise will now run counterclockwise, and vice versa. Thus, a curve defined as "clockwise" does not necessarily need to extend in a clockwise direction, but is simply a curve that is opposite in direction to a curve defined as "counterclockwise". Thus, it may be more generally considered that a "clockwise" curve may be a curve in a first direction, and a "counterclockwise" may be a curve in a second direction opposite to the first direction.

[0021] The fourth diameter may be smaller than the first diameter, the first diameter may be smaller than the second diameter, and the second diameter may be smaller than the third diameter.

[0022] The first curve may be an arc having an angle of 39°±15%, the second curve may be an arc having an angle of 114.5°±15%, and the third curve may be an arc having an angle of 76.4°±15%.

[0023] The first diameter may be 5 cm ± 15%, the second diameter may be 6 cm ± 15%, the third diameter may be 7.5 cm ± 15%, and the fourth diameter may be 1.5 cm ± 15%.

[0024] The catheter can be provided with a first thickness of the catheter towards the proximal end, a second thickness, and a third thickness at the distal end. The first thickness can be greater than the second thickness, and the second thickness can be greater than the third thickness. The first thickness can be a diameter of 6Fr, the second thickness can be a diameter of 5Fr to 6Fr, and the third thickness can be a diameter of 3.5Fr to 5Fr. It should be understood that, in contrast to the diameter of the curve used to describe the catheter (which refers to the diameter of the arc), the diameter describing the "thickness" of the catheter refers to the outer diameter of the cross-section of the catheter. This variation in thickness along the catheter can facilitate easier positioning of the electrode within the heart.

[0025] The at least one first electrode may include two electrodes disposed on the second curve. The at least one second electrode may include at least one electrode located on the third curve and at least one electrode located on the fourth curve.

[0026] The at least one second electrode may include at least two electrodes located on the third curve. The at least one sensor may be disposed on the second curve.

[0027] In this way, the curve of the elongated shaft can change between the proximal end and the distal end along its length, with the first counterclockwise curve being before the larger clockwise curve, and the clockwise curved tip having the smallest curve, wherein the diameters of the segmented curves are different, so that the curve segments of larger diameters are combined with the material (i.e., thickness and / or stiffness) to make the tendency of the catheter to bend greater than the curve segments of smaller diameters. In addition, when a guide wire with a certain stiffness passes through the inner lumen of the catheter, the stress generated in the catheter will stretch the arc of the catheter. The stress provides a larger stretch in the arc of the larger diameter, and the total stretching amount is also determined by the stiffness and thickness of the material of the catheter. The softer and / or thinner part of the catheter provides less resistance to stretching. In this way, the combination of the curve diameter and the material / structure of the curve will determine how the guide wire can be used to extend the extension range of the catheter, i.e., the distance from the at least one first electrode (proximal electrode group) to the at least one second electrode (distal electrode group). This enables the catheter to adapt to failing hearts of different sizes.

[0028] In addition, a lumen may be provided so that the guidewire may be passed completely through the catheter. In this way, the guidewire may be extended outside the catheter so that the guidewire may pass through the mitral valve and into the left atrium so that the tip of the guidewire may be placed in contact with the myocardium of the left atrium and then used to apply electrical stimulation pulses through the guidewire for artificial stimulation / pacing of the left atrium. Of course, more than one lumen may be provided within the catheter.

[0029] Furthermore, the combination of different directions of the curves enables efficient transmission of torque from the proximal end shaft to the distal end curve, which enables improved, easier and safer positioning of the electrode within the left heart.

[0030] The at least one electrode may comprise a plurality of electrodes arranged along the axis such that in use, at least two electrodes may be positioned in the patient's heart opposite to each other. Optionally, the at least one electrode is configured to be placed in contact with the patient's septal wall (and also to enable recording of conduction system biopotentials), and the at least one electrode is configured to be placed in contact with the patient's contralateral wall to enable measurement of the recorded delay in activation from the septum to the lateral wall.

[0031] In a second aspect, a system is provided, comprising

[0032] A catheter as described above;

[0033] Signal amplifier;

[0034] Stimulator; and

[0035] Data processing module;

[0036] The catheter is configured to communicate signals with a stimulator, an amplifier, and a data processing module, so that the electrodes and sensors can provide sensing data to the data processing module for further processing, and the electrodes can provide pacing to the patient's heart.

[0037] Such a system can be used to quickly and easily determine how a catheter moves around the heart, and therefore how moving the attached electrodes affects the function of the heart, and in particular whether pacing makes any significant difference in reducing dyssynchrony and / or dyssynergy.

[0038] The data processing module is configured to determine a characteristic response associated with the onset of myocardial synergy from events associated with a rapid increase in the rate of increase in pressure within the patient's left ventricle.

[0039] The sensor may be any kind of suitable sensor, or a combination of suitable sensors such as an accelerometer, a rotation sensor, a vibration sensor, and / or a pressure sensor. The sensor may be configured to provide data about the pressure within the heart to a data processing module, and wherein the data processing module is configured to filter the pressure data to identify a characteristic response associated with the onset of myocardial synergy. The characteristic response may include the beginning of a pressure rise above a pressure floor in a pressure signal filtered above a first-order harmonic of the pressure signal. The characteristic response may include the presence of a high-frequency component (above 40 Hz) of the pressure signal. The characteristic response may include a zero crossing of a bandpass filtered pressure trace. By filtering the pressure trace, associated noise may be removed, and points associated with the onset of myocardial synergy may be determined more accurately and reliably. It should be understood that a filtered pressure trace or a filtered pressure signal as referred to herein may equally refer to a filtered "raw" pressure trace, or any filtered derivative of the raw pressure trace.

[0040] Additionally or alternatively, the sensor can be configured to provide acceleration data from within the heart to the data processing module, and the data processing module can be configured to filter the acceleration data to identify a characteristic response associated with the onset of myocardial synergy. For example, the data processing module can be configured to calculate a continuous wavelet transform of the acceleration data to identify a characteristic response associated with the onset of myocardial synergy. The data processing module can be configured to calculate a center frequency of the continuous wavelet transform, wherein the characteristic response is a peak value of the center frequency. The data processing module is configured to average the center frequencies over multiple cardiac cycles. By filtering the acceleration trace, associated noise can be removed and points associated with the onset of myocardial synergy can be more accurately and reliably determined.

[0041] It should be understood that in addition to or as an alternative to the above methods, several additional methods are provided herein that can determine characteristic responses associated with the onset of myocardial synergy. The data processing module can be configured to perform one or more such methods.

[0042] For example, the increase in pressure within the heart (e.g., left ventricular pressure) over time for two different stimuli can be compared. For example, a pressure curve produced by right ventricular pacing and a pressure curve produced by biventricular pacing can be compared. The pressure rise caused by the two stimuli can be fitted together relative to their stimulation timing, and the pressure level is adjusted to fit the diastolic portion of the curve before ventricular pacing. The point at which the pressure curves produced by the stimuli begin to diverge from each other can then be detected, indicating the time of the onset of the synergistic effect of the stimuli that caused the earliest pressure rise.

[0043] Then, the portion of the pressure rise curve after the start time of the synergy on the pressure curve caused by the stimulus that causes the earlier pressure rise can be moved to fit the portion of the stimulated pressure rise curve that causes the relatively delayed pressure rise. The point on the stimulated pressure rise curve that causes the relatively delayed pressure rise (at which point the curve after the start of the stimulated synergy causes the earlier pressure rise) is the starting point of the synergy in the delayed pressure rise curve. The delay between the two determined points of the start of the synergy can then be calculated. Based on such calculations, a recommendation can be made as to which pacing scheme should be followed in the implanted pacemaker.

[0044] The above process may be automated and applied to data generated by any number of pacing regimens / stimulations, either by simple matching of curves (e.g., by fitting a template to the pressure trace using a least squares method) or by comparison of mathematical formulas representing the curves. In this way, explicit plotting of pressure curves and visual matching of curves may not be required, and the raw data may be analyzed to allow similar conclusions to be drawn.

[0045] In this way, an automatic detection can be made in the data of an exponential pressure rise until a peak dP / dt resulting from the onset of synergy. An exponential formula fitting the pressure curve can be automatically calculated, and the time at which the exponential formula fits one of the multiple curves can be determined.

[0046] There may be a template match and the time offset between the exponential formula and the template match may be calculated, or likewise a cross-correlation between other metrics.

[0047] The above method can also be performed using filtered pressure measurements.

[0048] Additionally or alternatively, the advancement of the onset of synergy can be detected by the advancement of the zero crossing of the bandpass filtered (e.g., 4 Hz to 40 Hz) pressure curve (Tp) with stimulation from a particular pacing regimen compared to another pacing. Such data can be used to indicate the presence of synergy with a particular pacing regimen, and therefore the expectation of receiving CRT with that pacing regimen.

[0049] The method may include calculating a baseline interval (B) by determining a time period between intrinsic atrial activation (Ta) and an associated zero crossing of a generated pressure curve (Tp). A corresponding time period (Tp1) may be calculated after pacing from a first electrode at a set pacing interval (PI1) after Ta, and the pacing interval is reduced until the interval from Ta to Tp is less than B. A corresponding time period (Tp2) may be calculated after pacing from a second electrode at a set pacing interval (PI2) after Ta, and the pacing interval is reduced until the interval from Ta to Tp is less than B. A corresponding time period (Tp3) may be calculated after pacing from the first electrode and the second electrode at a set pacing interval (PI3) after Ta, wherein PI3 is the same time interval as the lower of PI1 and PI2. By determining which pacing has the shortest corresponding time period Tp, the pacing scheme that results in the highest degree of synergy may be identified.

[0050] The data processing module is configured to identify reversible cardiac dyssynchrony by identifying a shortening of the delay in the onset of myocardial synergy due to pacing. Specifically, the data processing module can be configured to identify reversible cardiac dyssynchrony in the patient by identifying a characteristic response in data received from one or more sensors, using at least one sensor to measure the timing of an event associated with a rapid increase in the rate of increase in pressure within the patient's left ventricle, the event associated with the rapid increase in the rate of increase in pressure within the left ventricle being identifiable in each contraction of the heart.

[0051] The data processing module may be configured to measure the timing of an event associated with a rapid increase in the rate of increase in pressure within the left ventricle by;

[0052] processing signals from at least one sensor to determine a first time delay between a measured time of an identified characteristic response associated with a rapid increase in rate of increase of pressure within the left ventricle and a first reference time;

[0053] comparing a first time delay between a measured time of an identified characteristic response associated with a rapid increase in rate of pressure increase within the left ventricle and a first reference time to a duration of electrical activation of the heart;

[0054] identifying the presence of cardiac dyssynchrony in the patient if the first time delay is longer than a set fraction of the electrical activation of the heart;

[0055] after pacing is applied to the patient's heart via the at least one electrode and / or other electrodes;

[0056] The magnitude of the increase in left ventricular pressure associated with the rapid increase in rate of increase after pacing is calculated by

[0057] A second time delay between the identified characteristic response and a second reference time after pacing:

[0058] using the at least one sensor to measure the timing of an identified characteristic response associated with a rapid increase in rate of increase of pressure within the left ventricle following pacing; and

[0059] processing signals from the at least one sensor to determine a second time delay between a determined time of an identified characteristic response associated with a rapid increase in rate of increase of pressure within the left ventricle and a second reference time after pacing;

[0060] comparing the first time delay to the second time delay; and

[0061] If the second time delay is shorter than the first time delay, a shortening of the delay to the onset of OoS of myocardial synergy is identified, indicating that the time period until the point at which all segments of the heart begin to actively or passively stiffen has been shortened, thereby identifying the presence of reversible cardiac dyssynchrony in the patient.

[0062] In addition, the data processing module can be configured to determine the degree of concurrent activation of the heart being paced. Specifically, the data processing module can be configured to determine the degree of concurrent activation of the heart being paced via a method including:

[0063] Calculate VCG or ECG waveforms from the right ventricular pacemaker RVp and the left ventricular pacemaker LVp;

[0064] Synthetic biventricular pacing BIVP waveform pacing is generated by summing the VCG of the RVp and LVp, or by summing the ECG of the RVp and LVp;

[0065] Calculate the corresponding ECG or VCG waveform from the true BIVP;

[0066] Comparing the synthesized BIVP waveform with the real BIVP waveform;

[0067] Fusion time was calculated by determining the time point at which activations from the RVp and LVp met and the synthetic and true BIVP curves began to diverge;

[0068] in

[0069] The delay in fusion time indicates that a greater amount of tissue is activated before the electrically activated wavefronts meet, indicating a higher degree of parallel activation.

[0070] Furthermore, the data processing module is configured to determine an optimal number and position of electrodes for performing cardiac resynchronization therapy on the heart of the patient based on the nodes of the 3D mesh of at least a portion of the heart if the calculated degree of parallel activation of the myocardium is above a predetermined threshold. Specifically, the system may be configured to perform a method of determining an optimal number and position of electrodes for performing cardiac resynchronization therapy on the heart of the patient via a method comprising:

[0071] generating a 3D mesh of at least a portion of the heart from a 3D model of at least a portion of the patient's heart, or using a generic 3D model of the heart to obtain the 3D mesh of at least a portion of the heart, the 3D mesh of at least a portion of the heart comprising a plurality of nodes;

[0072] aligning the 3D mesh of at least a portion of the heart with the image of the patient's heart;

[0073] placing additional nodes on the 3D grid corresponding to locations of at least two electrodes on the patient;

[0074] calculating a propagation velocity of electrical activation between nodes of the 3D grid corresponding to locations of at least two electrodes;

[0075] Extrapolate the propagation velocity to all nodes in the 3D grid;

[0076] calculating the degree of parallel activation of the myocardium for each node of the 3D mesh; and

[0077] In case the calculated degree of parallel activation of the myocardium is above a predetermined threshold, the optimal number and positions of electrodes on the patient's heart are determined based on the nodes of the 3D grid.

[0078] The catheter may be configured to be provided into the patient's heart via arterial access, venous access, subclavian access, radial access, and / or femoral access, enabling provision of electrodes and sensors in use within the patient's heart. BRIEF DESCRIPTION OF THE DRAWINGS

[0079] Certain preferred embodiments will now be described, by way of example only, and with reference to the accompanying drawings, in which:

[0080] Figure 1 An exemplary catheter is shown.

[0081] Figure 2 Shown with Figure 1 Detailed illustration of an exemplary guidewire for use with a catheter.

[0082] Figure 3 Shows how to use a guidewire to steer the catheter.

[0083] Figure 4Various access routes for bringing a catheter into the heart are shown.

[0084] Figure 5 A cross section of a catheter is shown.

[0085] Figure 6 A more detailed view of the structure of the catheter is shown.

[0086] Figure 7 A block diagram of a system including a catheter is shown.

[0087] Figure 8 An exemplary analysis that may be performed on acceleration data in order to calculate the time of onset of synergy is shown.

[0088] Fig. 9 It shows that P 真实的 and P 读数 A graph of exemplary derivatives of to illustrate the effect of sensor calibration.

[0089] Fig.10 An exemplary catheter is shown, along with some exemplary dimensions to which it may extend.

[0090] Fig.11A The optimized catheter is shown before and after shape setting.

[0091] Fig. 11B A more detailed view of the structure of the catheter is shown.

[0092] Fig.12 The curve of a shape-set conduit and the effect of stress on the shape of the conduit are shown in more detail.

[0093] Fig.13 The curve of the shape-set catheter is shown in further detail.

[0094] Fig.14 The introduction of the catheter through the aortic valve and the coronary ostia is shown.

[0095] Fig.15 The distribution of properties throughout the catheter is shown.

[0096] Fig.16 Insertion of a catheter into the left ventricle is shown.

[0097] Fig.17 Shown is how to steer the catheter using a guidewire.

[0098] Fig.18 Further details of the catheter are shown, such as a cross section.

[0099] Fig.19 A system for processing data received by a catheter is shown. DETAILED DESCRIPTION

[0100] The catheters described herein may be used in methods such as those mentioned above, which may be performed prior to and during treatment of patients with possible desynchronized heart failure with a resynchronization pacemaker (CRT) to: 1) identify the presence of potential substrates that identify patients who may respond positively (there is a significant likelihood of resynchronization), 2) identify optimal locations for placement of pacing leads / electrodes, and 3) verify optimal electrode placement and resynchronization of the heart. While those skilled in the art will recognize the detailed principles and methods of these measures, such as those set forth in the aforementioned applications, exemplary methods in which the catheters may be used are briefly set forth herein.

[0101] While many of the figures described herein show many example dimensions and materials, it should be understood that these are example measurements and materials, and that any suitable measurements and materials may be selected to provide their functionality.

[0102] Currently, international guidelines based on describing indication criteria recommend that patients be implanted with a CRT pacemaker. These criteria are based on inclusion criteria in large clinical trials and include, among other things, symptoms of heart failure, reduced ejection fraction (heart function), and widening of the QRS complex of more than 120ms to 150ms (preferably left bundle branch block). However, currently only 50% to 70% of patients with one or more indications for CRT treatment actually respond to treatment. The reasons for these non-responders are multifaceted, but lead position, potential substrates (dyssynchrony), scarring and fibrosis, and electrode position are the most prominent reasons. By improving the detection of potential substrates indicative of dyssynchrony heart failure, the selection of responders can be improved (in terms of diagnostic capabilities) to optimize treatment (allowing therapy to be personalized for the patient).

[0103] First, it is desirable to detect and define the potential substrate (resynchronization potential) that defines whether a patient will respond to CRT, and whether the substrate is present in patients who meet standard inclusion criteria. When the substrate is present, implantation of a CRT pacemaker should proceed, but when the substrate is not present, then other applicable guidelines should be followed.

[0104] When a potential substrate is present, or even if a potential substrate has not yet been identified, an optimal position for the lead can be found based on a measurement of parallelism that takes scarring and fibrosis into account. The measurement of parallelism is performed by using a guidewire or lead with electrodes inside the heart (e.g., in a vein or chamber of the heart). The optimal position for placing the electrode is then recommended.

[0105] When the lead is in the optimal position, based on the determined optimal position and taking into account the measured parallelism from each node, the response can then be confirmed (through direct or indirect measurement of the onset of myocardial synergy), or alternatively rejected.

[0106] If the desired response is confirmed, a CRT pacemaker should be implanted. If a response is not confirmed, mapping and measurement of parallelism should be refined before final confirmation. If a response cannot be confirmed, implantation should be abandoned and an alternative implant should be performed following known guidelines.

[0107] It is contemplated that all of the methods mentioned above and herein may be used together, or equally may be used separately. In this regard, the presence of desynchronization and the potential for resynchronization may be detected, and resynchronization may be confirmed without selecting an optimal lead position, and likewise, an optimal lead position may be selected without confirming a potential substrate and resynchronization.

[0108] Thus, a system may be provided that includes a connection to electrodes that allow visualization of signals from the patient and measurement time intervals. Alternatively or additionally, a system may be provided that includes sensors and electrodes and allows visualization of a heart model and calculations based on the geometry of the heart model. Both systems may be used in combination in an operating room.

[0109] Implementation of the above-described systems and methods will be further described herein through exemplary implementations during surgery.

[0110] The patient is first brought into the operating room and the sensors and electrodes are affixed to the patient's body surface.

[0111] To determine the delay to the onset of myocardial synergy (OoS), one or more additional sensors may be utilized. For example, one or more of a pressure sensor, a piezoresistive sensor, a fiber optic sensor, an accelerometer, ultrasound, and a microphone may be utilized. The measurements from the additional sensors may be performed in real time and processed on site. If the delay to the onset of myocardial synergy is short relative to the QRS complex or short in absolute value (e.g., shorter than 120 ms or less than 80% of the QRS duration), implantation of a CRT device should not be performed. When the delay to the onset of myocardial synergy is measured to be long relative to the QRS complex or long in absolute value (e.g., longer than 120 ms or longer than 80% of the QRS duration), implantation of a CRT device should be performed.

[0112] The body surface electrodes are used to determine the degree of parallelism (the extent of parallel activation of the myocardium) by collecting the surface potentials of the inverse ECG activation map of the heart as described above, to determine the propagation velocity, and therefore the presence of desynchronization. Additionally or alternatively, electrodes implanted within the patient's heart may also be used to generate an electrical activation map, and therefore determine the presence of desynchronization. If the sensed activation pattern indicates that propagation through the tissue is too slow, or if sufficient parallel activation cannot be provided in the presence of scar tissue, then implantation of the CRT device should not be performed.

[0113] The patient is then prepared for surgery and draped with sterile pads. The surgery begins as usual, and a lead is placed in the patient's heart through a skin incision below the left clavicle and a subclavian vein puncture. The lead is then moved to position in the right atrium and right ventricle.

[0114] Desynchronization can then be introduced by pacing the right ventricle and can be confirmed when the delay of myocardial synergy is measured as discussed above. Sensors can be placed in the left or right heart chambers to determine the delay in the onset of myocardial synergy. In this way, the same calculations used previously can be performed to calculate the delay in the onset of myocardial synergy.

[0115] Once the wire is in place, the coronary sinus is cannulated, and angiography is performed in two planes to visualize the coronary veins.

[0116] Once the coronary veins are visualized, cannulation can be performed using a thin guidewire with an electrode at the tip or any catheter with one or more electrodes for mapping purposes. The measurements at time intervals are then used to characterize one or more of intrinsic activation, tissue properties, and vein properties. The coronary anatomy is then reconstructed in the software and the measurements are assigned to locations in the heart model relative to the reconstructed coronary sinus veins.

[0117] This data can then be used in a method performed outside the body to calculate parallelism in order to highlight the electrode locations with the highest parallelism values. Based on these measurements, the surgeon is advised to position the left ventricular (LV) lead with the electrode in the desired location / vein. Similar recommendations can also be made to reposition the right ventricular (RV) lead. Based on the measurements acquired and their processing, recommendations can also be provided to include other and / or additional electrodes to achieve higher parallelism. Other electrodes refer to other electrode locations outside of those available electrode locations (endocardium, surgical access), and additional electrodes refer to the use of multiple electrodes (more than two electrodes).

[0118] For the reasons described above, the coronary venous branches can now be visualized in two planes and the appropriate vein selected for placement of the left ventricular lead.

[0119] With the LV electrodes in place, the sensors can be used to determine the delay to the onset of myocardial synergy when pacing both the RV and LV. Different electrodes can be analyzed by repositioning the LV lead at different locations. The measurement of the delay to myocardial synergy can be performed using one or more of a pressure sensor, a piezoresistive sensor, a fiber optic sensor, an accelerometer, ultrasound, or by measured bioimpedance (when connected to the RV and LV leads). If the delay to myocardial synergy is not shortened, at least less than, for example, 100% of the intrinsic measured value, or when the bioimpedance measurement indicates that resynchronization has not occurred by abnormal movement, the proposed lead position should be abandoned. The intrinsic value measured from the onset of the QRS does not include the time from the onset of pacing to ventricular capture, and is therefore shorter by definition than the intrinsic value measured from the stimulation. Therefore, 110% will be close to the time interval measured with intrinsic activation. In this way, the intrinsic delay to the onset of synergy measured from the QRS complex can be calibrated by adding, for example, 15 ms to a value that reflects the time from the onset of the pacing spike to the electrical tissue capture that occurs when artificial pacing.

[0120] While pacing the RV, LV, or both, the VCG can be reconstructed and fusion time calculated. Fusion time can be further used to confirm the measured parallelism. Surface electrodes can be used for inverse modeling to measure fusion time. If the measured fusion time and measured parallelism are inconsistent, the reason for this discrepancy should be further investigated.

[0121] At the physician's discretion, an LV lead with multiple electrodes may be used. The use of multiple electrodes can be used to measure parallelism, and when increased parallelism is found, this increased parallelism can be confirmed using fusion time and by measuring the delay to the onset of myocardial synergy.

[0122] Once the lead is in the desired position, with the delay to the onset of myocardial synergy less than (e.g.) 110% of the initial intrinsic value and less than (e.g.) 100% of the biventricular paced QRS complex, the CRT can be implanted and the device generator connected and implanted in a subcutaneous pocket. If the lead is found not to capture the myocardium, or the position is determined to be suboptimal based on scientific empirical data or measured intervals (QLV), the lead is repositioned and retested before connecting the device generator. The skin incision is then sutured and closed.

[0123] The above system can be embodied in an overall system that includes a signal amplifier or analog-to-digital converter (ECG, electrogram and sensor signals), a digital converter (sensor signals), a processor (computer), software, an x-ray connector (by communicating directly with a dicom server or PACS server, or indirectly with a frame grabber and an angle sensor). The user can use a system with different sensors at his discretion. In addition, the system can also be used to solve other problems. For example, the system can be used for identification of the His region and placement of pacing leads in the His bundle, while also being used for additional measurements of the delay to the onset of myocardial synergy.

[0124] Exemplary Systems

[0125] Provided herein is a catheter having a configuration that can be used to detect dyssynergy resulting from dyssynchrony and to aid in the selection of appropriate patients for treatment. Such a catheter can provide specific use in the general method outlined above, by which patients can be identified as responders to CRT, an ideal pacing regimen can be selected, and response to treatment can be confirmed.

[0126] The catheter may include a cardiac catheter with a lumen for guidewire and saline flushing. The catheter includes one or more sensors. For example, the catheter may include vibration, pressure, acceleration and electrodes for sensing local and overall cardiac electrical signals. The catheter may be placed in the left ventricle or right ventricle through a venous or arterial access, and / or placed in a coronary vein. Electrodes may be used to sense electrical signals in a bipolar or unipolar manner (to a reference electrode on the catheter, or any other electrode connected to the patient's body), and electrodes may be used to pace the heart at different locations. The catheter is connected to a system for data processing by a cable or wirelessly. A guidewire may pass through the lumen of the catheter to increase the diameter of the distal end curve, and a guidewire may pass through the end of the lumen to contact with cardiac tissue, and serve as a sensing and pacing electrode.

[0127] When the catheter enters the heart chamber, the electrogram provided from the catheter's sensor can be used to measure the electrical delay from one electrode to another electrode (or to an electrode outside the catheter), and thereby determine the electrical activation time. In addition, using the catheter, other factors such as vibration, pressure, and acceleration can be measured, and the signal is then filtered to receive measurements that can be used to determine the onset of synergy in the heart. Therefore, the catheter can be used to obtain measurements that can be further used to measure the degree of resynchronization and the likelihood of resynchronization. Similarly, the catheter can be provided as part of a system that, for a given set of electrode positions, can measure all the data needed to calculate the time to the onset of synergy. Therefore, a system including a catheter can be used to quickly and easily determine the likelihood of resynchronization for a patient.

[0128] This catheter can provide multiple uses. As described above, the catheter can be used to obtain all measurements for detecting the onset of synergy after pacing and determine the resynchronization possibility of the patient. For example, this method for determining the onset of synergy is defined above or in GB1906064.9, PCT / EP2020 / 062149 and the national phases generated therefrom. The catheter can be used to take measurements to determine the degree of parallel activation. For example, this method for determining the degree of parallel activation is described above or in GB1906055.7, PCT / EP2020 / 062146 and the national phases generated therefrom. Similarly, the catheter can be used to take measurements to determine the fusion time in the heart. For example, this method for determining the fusion time of the heart is described above or in GB1906054.0, PCT / EP2020 / 062152 and the national phases generated therefrom. The catheter may additionally be provided with a data processing module which may additionally process data received from the catheter to provide a measure of any of the above values ​​without requiring further post-processing of the data.

[0129] Such a catheter 2600 may be Figure 1 The catheter includes one or more electrodes 2601, one or more sensors 2602, a shaft 2603, communication devices 2604 and 2605, a hemostatic valve 2606, and a guidewire 2607. The catheter extends to a distal end 2608.

[0130] The sensor may be any desired sensor. For example, where the catheter is used to determine a delay in the onset of myocardial synergy, it may be desirable for the sensor to be a pressure sensor so that the pressure within the heart, and therefore the pressure changes within the left ventricle, can be measured invasively. Additionally or alternatively, the sensor may include a piezoelectric sensor, a fiber optic sensor, and / or an accelerometer sensor. The sensor may detect events such as cardiac contraction, onset of synergy, valvular events, and pressure and transmit them to a receiver connected to a processor.

[0131] The distal end 2608 of the catheter 2600 is a floppy pigtail so that the electrode 2601 located at the curved distal end can be moved by advancing a relatively stiff guide wire 2607 along the axis of the catheter. By advancing the guide wire through the catheter 2600, the diameter of the curve provided at the distal end 2608 of the catheter 2600 increases. This allows movement of the distal end 2608 of the catheter 2600, and therefore movement of the electrode 2601. Figure 1 Such variable positions are shown in dashed lines 2611. Additionally, the distal end 2608 of the catheter 2600 may be provided with a soft tip for atraumatic contact with the lateral wall endocardium.

[0132] The communication device 2604 can transmit data received from the electrode 2601, and the communication device 2605 can transmit data from the sensor 2602. As shown, these can be provided as physical wires to be plugged into an external data processing module. Alternatively, they can provide wireless transmission to transmit data without a physical connection. The shaft of the catheter 2600 can have any suitable diameter. For example, the shaft can be a 6Fr shaft. In addition, saline flushing can be provided through the hemostasis valve 2606.

[0133] exist Figure 2 A more detailed view of the guidewire 2607 can be seen in FIG. A stiffer body 2701 is provided at the proximal end of the guidewire 2607, and then a flexible tip 2702 is provided at the distal end. This arrangement allows for more fine adjustment of the position of the catheter and the electrodes and sensors positioned thereon.

[0134] Figure 3 2607 is shown for manipulating the catheter 2600, and more specifically, the electrodes and sensors disposed thereon. As shown, the guidewire 2607 is introduced through the proximal end of the catheter 2600. The guidewire extends through the catheter 2600 toward the distal end 2608. As can be seen, the catheter 2600 is a floppy pigtail shape such that as the relatively stiff guidewire 2607 is advanced through the catheter 2600, the diameter of the curve provided by the catheter 2600 increases, as shown in FIG. Figure 3 The stiffer body 2701 near the proximal end of the guidewire 2607 provides a more pronounced expansion of the catheter curve than the flexible tip 2702. This provides more accurate control of the position of the electrode 2601 (and other sensors 2602) on the catheter 2600.

[0135] Catheter 2600 can be placed at various locations within the heart such as Figure 4 As shown. For example, a catheter can be provided through position A to provide arterial access to the heart chamber, or a catheter can be provided through position B to provide venous access to the heart chamber. Through position A, the catheter (and embedded sensors and electrodes) pass through the septum 2901 toward the contralateral wall 2902, so that the electrodes can be placed in the septum and the contralateral wall. Through position B, the catheter can pass through the coronary sinus ostium 2903 and the coronary vein 2904, so that the catheter (and electrodes) pass through the venous system into the coronary vein. Alternatively, the catheter can be provided through a subclavian access, a radial access, or a femoral access. The catheter is configured to be positioned in the left heart chamber, wherein the electrodes are opposite each other at the septum and the contralateral wall, and the sensor is disposed within the chamber. The electrodes will be provided to contact the tissue.

[0136] Figure 5Two cross-sections of the catheter 2600 are shown. As described above, the catheter 2600 can be provided with any suitable diameter d (such as 5Fr). The catheter 2600 is provided with at least one internal lumen 3001 through which a guidewire can pass. In addition, a saline flush can be provided through the internal lumen 3001. The internal lumen can also be provided with any suitable diameter, such as 0.635mm (0.025 inches). The catheter 2600 is further provided with a plurality of channels 3002 for electrode wires and a plurality of channels 3003 for sensor wires, which are connected to the embedded sensor 2602.

[0137] exist Figure 6 A more detailed view of the structure of the catheter 2600 is seen in . As described above, saline flushing can be provided through the hemostasis valve 2606. The catheter 2600 is provided with a rigid proximal end 3101, a moderately stiff middle section 3102, and a flexible tip 3103 located at the distal end of the catheter.

[0138] Figure 7 A system 3200 for sensing and processing data is shown, which includes a catheter, such as one of the catheters described herein. The catheter 2600 is in signal communication with a stimulator 3201, an amplifier 3202, and a processor 3206. As described above, the catheter 2600 includes an electrode 2601 and a sensor 2602. The electrode is in signal communication with the stimulator 3201 and the analog converter 3203 of the amplifier 3202 through a communication device 2604. The sensor 2602 is in signal communication with a receiver and converter 3204, and is additionally in signal communication with the analog converter 3203 of the amplifier 3202. The amplifier 3202 then provides an output to the processor 3206. For example, the amplifier 3202 can be connected to the processor 3206 via a fiber optic cable 3205.

[0139] The processing module 3206 can be configured to acquire data collected by the catheter 2600 and further process the data to provide a meaningful assessment of the patient's cardiac function. For example, the data processing module can be configured to calculate the delay of the onset of synergy, fusion time, or a measure of parallelism of the patient's heart.

[0140] For example, the catheter may be provided with at least one piezoelectric sensor 2602 (and / or optical sensor 2602, and / or accelerometer 2602) configured to directly measure pressure within the heart. Using such information, the catheter 2600 and processing module 3206 may be configured to automatically and reliably detect a point associated with the onset of synergy that is distinct from and occurs at a point between the pre-ejection interval (PEI) and the electromechanical delay (EMD).

[0141] For example, while this may be associated with a rapid pressure rise resulting from the onset of synergy, the onset of synergy may be better and more reliably represented by a filtered pressure trace. As will be appreciated by those skilled in the art, a filtered pressure trace may refer to a filtered raw pressure trace or equivalently a filtered derivative pressure trace, referring to any number of derivatives. Thus, the system 3200, and more specifically the piezoelectric sensor 2602 of the catheter 2600, and the processing module 3206 may be configured to detect pressure changes within the heart, optionally calculate the derivative of the pressure change, and filter the pressure trace to give an accurate representation of the onset of synergy. This may be achieved by bandpass filtering at, for example, 2 Hz to 40 Hz to remove the first order harmonics of the pressure wave. As described above, the curve has a linear overshoot resulting from the onset of synergy and crossing zero at the peak dP / dt. For example, filtering at a bandpass of 2 Hz to 40 Hz or 4 Hz to 40 Hz removes low, slow frequencies associated with dyssynergy, and the onset of synergy can be viewed as the onset of a pressure increase leading to or directly preceding aortic valve opening or maximum pressure.

[0142] This change in the rate of pressure increase is due to the formation of an incremental and exponential cross-bridge as the tension of the passively stretched segment increases, either due to depolarization or due to the elastic model reaching a near maximum value. Rapid cross-bridge formation with isometric or eccentric contractions results in a high frequency component in the pressure curve spectrum that reflects the onset of synergy. This phase of the cardiac cycle can be seen when the LVP is filtered with a high pass filter above the first or second harmonic. The filtered characteristic waveform has a nearly linear increase from the onset of synergy to the zero crossing and continues to increase linearly until the aortic valve opens. The linearly increasing line reflects the period of time with synergy, crossing zero midway through the phase, which corresponds to the peak dP / dt as described above, and the onset of synergy is reflected at the point where this line begins to rise above the floor of the filtered pressure curve or is at its lowest point. In addition, the catheter 2600 and processing module 3206 can be configured to use the high frequency components (above 40 Hz) of the pressure trace to identify the onset of synergy in the medium frequency filtered (4 Hz to 40 Hz) signal because the high frequency components identify the pressure rise before the zero crossing.

[0143] One or more of these points in the pressure trace that captures data filtered from the piezoelectric (or other optical) sensor 2602 of the catheter 2600 (the start of a linear increase in the bandpass filtered pressure trace, a zero crossing in the bandpass filtered pressure trace, the start of a high frequency pressure component of the pressure trace) can be utilized by the data processing module 3206 to accurately and reliably indicate the onset of synergy. Additionally or alternatively, the sensor 2602 may include an accelerometer that acquires accelerometer data within the heart, and the onset of synergy is determined from such data, e.g., as described above and Figure 8 . The raw acceleration data 301 may be bandpass filtered to yield data 3502, and a wavelet scalogram 3503 may be generated from such data, which shows a spectrum over time. A center frequency trace fc(t) 3504 is then calculated from the wavelet scalogram, as seen in graph 3504. For each cycle of the heart, the time of peak fc(t) is averaged and extracted for each cycle, and the start time (Td) of the synergy may be determined, as seen in graph 3506. The time of the start of the synergy may be measured from any suitable reference time, such as the onset of the QRS, 3507.

[0144] It should be understood that any of the measures for detecting the onset of synergy (or a point directly related thereto) considered above and herein may be combined to provide a more accurate measure of the onset of synergy and / or how synergy changes with treatment. For example, a measure of the time of, or a point related thereto, the onset of synergy calculated by filtering the pressure data before / after treatment may be compared and contrasted to the onset point of synergy calculated using raw acceleration data within the heart before / after treatment. In this way, more than one measure may be used to verify a reduction in the time of onset of synergy (thereby indicating the presence of a reversible cardiac dyssynchrony).

[0145] By utilizing any of the above metrics, the system can therefore automatically determine for each position of the catheter, and therefore for the electrodes, how the time before the onset of synergy varies. In this way, the system can give immediate (or near immediate) feedback on the efficacy of various electrode placements in reversing dyssynchrony and dyssynergy.

[0146] In one example, as an indication of the time of the start of synergy, a zero crossing from the filtered signal or a template match from the filtered signal can be detected within a time range from a reference time. For example, a zero crossing within a time range of ±40ms from the end of the QRS is measured (in order to ensure the first zero crossing, i.e., the zero crossing associated with the same heart beat). Alternatively, the start of synergy can be indicated by the timing of the lowest point (i.e., the point where the pressure starts to increase from the pressure floor) and the high-frequency component. It should be understood that both of these measures (and other measures) can represent the start of synergy, i.e., the point at which all segments of the heart begin to stiffen actively or passively. This is actually manifested in the beginning of a rapid rise in pressure within the heart.

[0147] Although the onset of synergy is manifested as an increase in pressure within the left ventricle as the point at which all segments of the heart begin to stiffen actively or passively, it will be appreciated by those skilled in the art that this point may also be measured indirectly in other locations. In this manner, in addition to being positioned within the left heart chamber, the catheter may be positioned, for example, within the coronary veins or within the right heart chamber to provide similar measurements indicating the onset of synergy, while appropriately filtering the signal.

[0148] In summary, it can be said that the catheter measures pressure and / or vibration, and different filters can then be applied to evaluate the pressure / vibration, as well as the electrical signal detected by the catheter to determine if there is a synchronization disorder. While a reduction in the delay to the onset of synergy (e.g., calculated as described above) indicates the presence of a synchronization disorder, a prolongation of the stimulation interval when compared to the baseline (i.e., the absence of stimulation) identifies the possibility of iatrogenicity. This situation can be detrimental to the patient's health and should be avoided.

[0149] Of course, the methods that can be applied by the catheters described herein are not limited to the methods discussed herein. The catheters herein can provide broader use for methods other than detecting the onset of synergy, determining optimal electrode positions and numbers, and measuring fusion time.

[0150] Effect of sensor calibration on dP / dt:

[0151] Advantageously, when using the pressure derivative associated with the measured value of the onset of the synergy, the sensor of the catheter may not require a calibration time event.

[0152] In theory, the offset and gain of the pressure signal should not affect the results when dP / dt = 0 or when dP / dt reaches its peak. The offset will not affect when dP / dt = 0 or when dP / dt reaches its peak because the derivative of the offset will become zero. Although the gain will affect the value and slope of the pressure sensor signal, the gain will not affect when the maximum / minimum value of the pressure signal occurs (when dP / dt = 0) or when the maximum / minimum slope of the pressure signal occurs (when dP / dt reaches its peak).

[0153] This effect is demonstrated in the following simplified example, which shows how neither offset nor gain affects a periodic pressure signal.

[0154] For example, if the real pressure signal is represented by the following equation:

[0155] P true sin(60t)

[0156] And the catheter has an offset of 100mmHg, with a gain of 5 times the actual signal. Then the pressure signal reading will be characterized by the following equation:

[0157] PP reading = 5sin(60t)+100

[0158] Even given the difference between the true pressure signal and the read pressure signal, the derivatives of the two equations with respect to time (t) are still:

[0159]

[0160] Although the amplitudes of the two dP / dt equations are different, the times when dP / dt = 0 and when dP / dt reaches its peak are similar for both equations (respectively and where n is any integer value) are equal. This is Fig. 9 , which shows the P from the example given above. 真实的 and P 读数 From this example, we can see that for P 真实的 and P 读数 In both cases, dP / dt=0 and dP / dt reaching its peak occur simultaneously.

[0161] It should be noted that signal changes due to temperature, drift, and atmospheric pressure are all time dependent, meaning that, in theory, these changes could have some effect on the time when dP / dt = 0 or when dP / dt reaches its peak. However, the largest differences due to temperature and drift will occur when the catheter is first introduced into the body, as the sensor is transitioning from a dry state at room temperature to a "wet" state at body temperature. When the catheter is deployed / positioned and data analysis begins, the amplitude and frequency of changes due to temperature, drift, and atmospheric pressure are minimal compared to the amplitude and frequency of the pressure in the heart. Therefore, even without correcting for changes due to temperature, drift, and atmospheric pressure, the effect on dP / dt = 0 or when dP / dt reaches its peak will be negligible.

[0162] Fig.10An exemplary catheter is shown in FIG. 1 , along with some exemplary dimensions to which it can extend. In order to provide electrodes 2601 and sensors 2602 at desired locations within the heart, a flexible tip can be provided with a small diameter d. The middle portion of the catheter can be provided with a large diameter D. As an example, diameter d can be of the order of 1.5 cm, and diameter D can be of the order of 6 cm. The total length of the catheter can be of the order of 130 cm. The electrode 2601 closest to the tip of the catheter can be 1 mm wide and can be positioned at a distance w from the tip, such as 3 cm. The two electrodes closest to the tip can be set 8 mm apart. The sensor 2602 can be set at a distance x from the tip of the catheter, such as 11 cm. Another electrode 2601 can be set at a distance y from the tip of the catheter, such as 13 cm. The electrodes can be provided at a distance z, which can also be, for example, 8 mm. Of course, the dimensions are exemplary, and other dimensions can be envisioned.

[0163] In summary, in the above-mentioned system, the distal segment of the catheter is suitable for positioning so that the electrodes are opposite to each other in the heart. The distal segment has an area intended to contact cardiac tissue. The distal segment carries one or more electrodes and one or more sensors (e.g., pressure sensors, piezoelectric sensors, fiber optic sensors, accelerometers) located proximal to the distal end of the catheter. The sensor provides data about cardiac contraction, the onset of synergy, valve events, and pressure to a receiver connected to a processor. The electrode is connected to an amplifier, which is connected to a processor. The electrode is connected to a stimulator. The processor can analyze the received data to determine a point related to the onset of synergy, and use this point to determine whether there is desynchronization and desynchronization, and then further determine whether the stimulating electrode causes the reversal of desynchronization and desynchronization.

[0164] When the catheter is properly positioned in the left heart chamber with the electrodes facing each other at the septum and contralateral wall and the sensor within the chamber, with each heart beat, a voltage gradient is recorded between each electrode and a reference electrode. This voltage gradient represents the electrical activation of the heart. In addition, and in accordance with the above, the sensor records an event associated with the onset of synergism, i.e., an event associated with a rapid increase in the rate of rise of pressure within the left ventricle, which reflects the point at which all segments of the heart begin to maximally stiffen, either actively or passively. The timing of this event is compared to the electrical activation, and the presence or absence of dyssynchrony and dyssynergia is recorded.

[0165] The heart can then be stimulated from one or more electrodes. With each heart beat, a voltage gradient is recorded between each electrode and a reference electrode, which voltage gradient, as described above, can represent electrical activation of the heart. One or more sensors again record events associated with the onset of synergy. The new set of time events can then be compared to the first set of events, and the presence or absence of resynchronization is recorded.

[0166] Advantageously, using such a system, such measurements for various locations of electrodes can be determined quickly and efficiently. In this way, not only can it be determined whether a patient is indeed a possible responder to cardiac resynchronization therapy, but the ideal number and location of electrodes can also be quickly determined.

[0167] Optimized system

[0168] In view of the above, an optimized catheter and system has been developed to more conveniently and accurately place electrodes and / or various sensors within the heart, thereby enabling more accurate determination of various measurements, such as that of the onset of synergy.

[0169] Curves may be discussed herein as having a radius or diameter. Such curves may be defined by an arc of a circle having a given radius or diameter. Therefore, it should be understood that when a curve is discussed as having a radius or diameter, it will be understood that such a radius / diameter may also be considered to refer to the corresponding radius / diameter of a circle on which the curve may be defined. It should also be understood that any angle and radius / diameter mentioned may refer to the angle / diameter of the curve that "sets" the catheter, and may change under external stress during use. In addition, although the curves are described herein as clockwise and counterclockwise to clearly distinguish the directions of the curves, it should be understood that these directions may be flipped. For example, if the catheter is flipped, a curve that was previously clockwise will now run counterclockwise, and vice versa. Therefore, a curve defined as "clockwise" does not necessarily need to extend in a clockwise direction, but is merely a curve that is opposite in direction to a curve defined as "counterclockwise". In addition, although various dimensions are included in the accompanying drawings, it should be understood that these dimensions are not restrictive and may vary.

[0170] Such a catheter 1100 may have Fig.11A , which shows the shape of the catheter 1100 before and after shape setting (i.e., in its completely straight, maximum length and in its final use). Fig.11A Some exemplary dimensions of the catheter 1100 can be seen in addition. It can be seen that the catheter can have an overall length of about 110 cm when completely straight, with dimensions and spacing between features such as Fig.11A The catheter 1100 extends from a proximal end 1110 to a distal end 1120 .

[0171] The catheter has three sections 1121, 1122, 1123, each of which has a different stiffness. The proximal section 1121 closest to the proximal end 1110 of the catheter can be the hardest (e.g., including Nylon 11 or 12 or materials commonly used for intracardiac angiography catheters, such as polyamide, polyurethane, Teflon, and combinations thereof), and the distal section 1123 at the distal end 1120 can be the most flexible (e.g., including Pebax 35D). The middle section 1122 has a stiffness between the other two sections (e.g., including Pebax 75D or 55D). The distal section 1123 can extend about 4 cm from the distal end 1120 of the catheter 1100. The middle section 1122 can extend about 12 cm from the distal section 1123. The proximal section 1121 can extend the remaining length of the catheter, for example, about 94 cm.

[0172] exist Fig. 11B As can be seen in FIG. 1 , to provide this variable stiffness, the catheter may include a central extrusion 1131 extending through all three sections 1121 , 1122 , 1123 . The central extrusion 1131 may include one or more lumens extending therethrough. Fig. 11B In the example of the central extrusion 1131 is a multi-lumen extrusion. Then, in order to provide different relative stiffness between each section 1121, 1122, 1123, the central extrusion can be covered by one or more covers or jackets 1132 of different materials at each section. For example, the central extrusion 1131 can include Pebax 63D, relatively hard Pebax 75D, or relatively soft Pebax 55D, and all are the same material. In order to provide a hard proximal end 1121, a jacket with or without braided wire made of a relatively hard material such as Nylon 11 or 12 can be set around the proximal end of the catheter to harden the central extrusion at the proximal end. Then, the middle section 1122 can be covered by a jacket of a material (such as Pebax 75D or 55D) with a relatively lower stiffness than the proximal end. Finally, the flexible top 1123 can be covered by a material (such as Pebax 35D) with even lower stiffness. By providing this common central extrusion throughout the catheter, and varying the stiffness by having an outer jacket of varying stiffness, the catheter can be manufactured more easily. Fig. 11B As can be seen in the figure, one or more of the materials of the catheter may be provided with a portion of barium sulfate (BaSO4). For example, the material of one or more of the jackets surrounding the proximal end 1121, the middle section 1122 or the distal end 1123 may include 20% BaSO4.

[0173] exist Fig.11AAs can be seen in FIG, the catheter 1100 may include five electrodes 1101, 1102, 1103, 1104, and 1105. The five electrodes may be arranged in two groups, wherein three electrodes 1105, 1104, and 1103 are arranged relatively close to the distal end 1120 of the catheter, and the remaining two electrodes 1102, 1101 are arranged away from the distal end 1120 of the catheter. The distance between the electrodes between the two groups of electrodes may be selected so that at least one electrode of the group of electrodes positioned away from the distal end may contact the septum, while at least one electrode of the group of electrodes positioned closer to the distal end may contact the free wall. In addition, the distal electrodes may have a spacing narrower than the spacing shown. By providing a narrow spacing between at least one pair of distal electrodes, bipolar sensing may be achieved, thereby improving spatial resolution and eliminating far-field sensing. In this way, the signals received by the electrodes may be used to detect local electrical activation, and thus ensure accurate assessment of the electrical delay from the reference (start of QRS) to the zone.

[0174] For example, the Euclidean distance between the two sets of electrodes may be in the range of 6.5 cm, which may be increased to 9 cm in the case where a rigid guidewire is inserted into the lumen of the catheter.

[0175] When the guide wire is inserted into the inner lumen of the catheter and the catheter is correctly positioned in the heart, as shown in all the figures, the guide wire can be advanced through the catheter because the tip of the catheter points in the direction of the left atrium. In this way, the guide wire can pass through the catheter and then through the mitral valve and into the left atrium. When the tip of the guide wire is placed in contact with the myocardium of the left atrium, the stimulator can then be connected to the proximal end of the guide wire and an electrical stimulation pulse is applied through the guide wire for artificial stimulation / pacing of the left atrium.

[0176] For example, when measured on the catheter before shape setting, the electrode 1105 can be arranged about 3 cm from the distal end 1120 of the catheter 1100, and thus in the distal section 1123. The electrode 1104 can be arranged about 4 cm from the distal end 1120. Therefore, the electrode 1104 can be located on the distal section 1123, the middle section 1122, or between the distal section 1123 and the middle section 1122. The electrode 1103 can be arranged about 5 cm from the distal end 1120, and thus in the middle section 1122. These electrodes 1105, 1104 and 1103 can form a first set of electrodes, which are arranged closer to the distal end of the catheter 1100 than the second set of electrodes 1102, 1101. Of course, the first set of electrodes and the second set of electrodes can include more or fewer electrodes.

[0177] A pressure sensor 1106 may be disposed between the first and second sets of electrodes and may be disposed approximately 11 cm from the distal end 1120 of the catheter 1100. Alternatively, the pressure sensor 1106 may be disposed closer to the distal end of the catheter, or at the distal end of the catheter, for ease of manufacturing.

[0178] Electrode 1102 may be disposed approximately 13.5 cm from a distal end 1120 of catheter 1100 , and electrode 1101 may be disposed approximately 15 cm from a distal end of catheter 1100 , and thus both electrodes may be located in intermediate portion 1122 .

[0179] The catheter can then be set into the desired shape, such as Fig.12 1 . The catheter 1100 may be described with reference to four segmented curves (curve 1, curve 2, curve 3, and curve 4). Described starting with the proximal end 1110, once set, the catheter may be bent counterclockwise at a relatively small diameter (typically in the range of 4 cm to 6 cm) to form curve 1. The catheter 1100 may then bend clockwise at a larger diameter (typically in the range of 5 cm to 7 cm) to form curve 2, and then begin to bend further clockwise at a larger diameter (typically in the range of 7 cm to 9 cm) to form curve 3. The catheter 1100 may then bend in a final tight clockwise curve to form curve 4 having a small diameter (typically in the range of 1 cm to 3 cm).

[0180] exist Fig.12 As can be seen in FIG. 1 , when a catheter is introduced into a patient through, for example, arterial access, venous access, subclavian access, radial access, and / or femoral access, it may experience forces on the axis of catheter 1100. For example, when introduced through parallel walls, the catheter may contact the walls on curves 2 and 3, but the catheter may also contact the wall on curve 4. The combined force will force the larger diameter segment (i.e., curve 3) inward.

[0181] Fig.13The curves of the catheter 1100 are shown in more detail, and it is more clearly shown how each curve relates to an arc of a circle with a given radius / diameter. As briefly described above, the first curve (curve 1) closest to the proximal end 1110 bends counterclockwise to form an arc of approximately 39°±15% of a circle with a radius of approximately 2.5 cm±15%. The catheter then bends clockwise (curve 2) to form an arc of approximately 114.6°±15% with a radius of approximately 3 cm±15%. The curve is then followed by another curve (curve 3), also clockwise, but with a larger radius of approximately 3.75 cm±15%, to form an arc of approximately 76.4°±15%. Finally, the catheter 1100 ends with a final clockwise curve (curve 4) having a radius of approximately 0.75 cm±15%.

[0182] exist Fig.14 As can be seen in , such a curve setting allows the catheter 1100 to easily pass through, for example, the aortic valve. This can be achieved by having the distal end curved and not engaged in the coronary ostia, or alternatively, when the large bend (i.e., curve 3 above) is resisted by stress (as shown and described above) and travels along the wall of the ascending aorta, it can be rotated by the operator to allow the valve to pass between the cusps and be pushed into the left heart chamber when the valve opens. This is particularly beneficial when providing a catheter within the heart to perform the above method, and particularly when determining the onset of synergy.

[0183] Specifically, the combination of varying stiffness along the catheter and the presence of one or more lumens through which a guidewire may pass to provide stiffness to the catheter enables safe and effective placement of the catheter within the left heart.

[0184] First, the catheter can be placed on a line that already passes through the aortic valve. Second, the curve of the catheter is similar to the curve of the aortic arch. In this way, when the curved tip of the catheter is pushed forward against the blood flow in the aorta (retrograde), it will engage with the aortic valve without entering the coronary arteries, and can then pass through the valve (rotate) to align with the opening of the tricuspid (or bicuspid) aortic valve and enter the left heart. Third, the tip of the catheter can engage with the aortic valve so that the tip of the catheter is pushed upward into the ascending aorta in a manner that allows the larger curve of the catheter to engage with the aortic valve and rotate, so that the tip of the catheter can pass through the aortic valve by aligning with the opening of the aortic valve, which is in Fig.14 It can be seen in.

[0185] Once in the left ventricle, the stiffness and various diameters of the curve of the catheter can be manipulated by inserting a rigid guidewire, and the catheter can be rotated to position the electrode in a diametric location within the left heart. This positioning allows stimulation at different and distant locations of the left heart chamber through the electrode.

[0186] In addition, the shape of the catheter enables insertion into the coronary vein and its branches. The shape of the catheter is adapted to the curvature of the coronary vein, and, for example, a 0.014" (0.36mm) coronary guidewire can be passed through the catheter when the catheter is in the coronary vein. The guidewire can then be used to cannulate the branch of the coronary vein, subsequently allowing the catheter to be guided over the guidewire into the cannulated branch. The distal electrode can then be used to stimulate the epicardial region of the left heart chamber covered by the cannulated branch, while the proximal electrode can be used to stimulate the atrium. The pressure sensor can then capture sound signals from the vibrations of the heart valve, which can be used to detect the onset of synergy, and pacing can be guided to resynchronize the left heart chamber. For example, pacing can be guided by atrioventricular delay so that a fusion optimized interval technique can be used, as understood by those skilled in the art.

[0187] Fig.15 The distribution of various properties across an optimized catheter is shown from the proximal end 1110 to the distal end 1120. Each property is shown as distributed along the length of the catheter. Fig.15 The grid on the graph is set to represent a scale where each large square represents an increment of 1 cm.

[0188] Considering each attribute in turn, generally speaking, a catheter may be provided with two colors, a first color extending from the proximal end 1110, and a second color on the distal tip.

[0189] Similarly, the catheter can be configured such that the proximal end 1110 is non-radiopaque and only the distal end is radiopaque.

[0190] The catheter may be provided with a first size, such as 6 Fr, at the proximal end 1110. Then, as the catheter extends toward the distal end 1120, the catheter may become smaller to reach a second size, such as 5 Fr. Then, at the distal end of the catheter, the catheter may be provided with a third size, such as 3.5 Fr. As an example, and as Fig.15 As shown, the third dimension may extend about 2 cm from the distal end 1120, and the second dimension may extend about 8 cm from the end of the third dimension. The first dimension then extends from the second dimension to the proximal end 1110 of the catheter. This variation in the diameter (thickness) of the catheter may help allow the catheter's electrodes to be placed within the heart in a safe, quick, and easy manner.

[0191] Then, in Fig.15In the example of , regarding stiffness, at the proximal end 1110, the catheter can be provided with a braid, which in turn provides a first stiffness. Then, a second stiffness is provided, which extends about 3 cm. Extending from the second stiffness is a third stiffness, which extends about 11 cm. Finally, a fourth stiffness is provided from the end of the third stiffness, which extends about 2 cm to the distal end 1120 of the catheter. Typically, the stiffness of the fourth stiffness will be less than the third stiffness, which in turn is less than the second stiffness.

[0192] Finally, in Fig.15 11. The curvature of the catheter is shown in FIG. The shaft has no curvature at the proximal end 1110. Curve 1 then extends for a length of about 1.7 cm (i.e., the circumference of the arc). Curve 2 extends from curve 1 in the opposite direction for about 6 cm. Curve 3 then extends for about 5 cm and ends at curve 4, which extends for about 3 cm to the distal end of the catheter. The relative position of each electrode and pressure sensor is also indicated here.

[0193] While the above broadly describes the attributes of an exemplary catheter, those skilled in the art will recognize that the teachings presented herein are not strictly limited to such dimensions and, as such, each of the above attribute profiles may be provided separately in an exemplary catheter, i.e., the attributes are not inseparable from one another.

[0194] Specifically, the combination of a harder and / or thicker material in the sections with the smaller radius of the initial curve (i.e., curves 1 and 2 identified above) and a softer material with the larger curve (i.e., curves 2 to 3 identified above) enables improved performance of the catheter, which in particular allows for placement of electrodes within the heart in a safe, quick and easy manner, for example, as described above with reference to Fig.14 Said. Then, by providing a relatively soft and narrow distal end, when a relatively hard guide wire is introduced into the distal end via the lumen, the softer distal tip is allowed to extend easily. The lumen (and the associated guide wire) allows the diameter of the distal curve to be changed, while there is a larger spacing between the electrode groups, and the reach of the distal electrode can also be extended when the guide wire passes through the lumen. When the guide wire is inserted, the softer distal tip is fully extended, allowing the catheter to advance along the guide wire in the artery / blood vessel. In addition, as described above, the guide wire can extend outside the catheter so that the guide wire can pass through the mitral valve and enter the left atrium, so that the tip of the guide wire can be placed in contact with the myocardium of the left atrium, and then used to apply electrical stimulation pulses through the guide wire to artificially stimulate / pacing the left atrium.

[0195] Fig.16The catheter 1100 is shown inserted into a left ventricle having a septum 1610 and a free wall 1620. It can be seen that the shape of the catheter profile ensures that at least one of the electrodes 1101, 1102 contacts the septum and at least one of the electrodes 1103, 1104 and 1105 contacts the free wall 1620, regardless of whether the ventricle is small (i.e., having a free wall 1621), normal size (i.e., having a free wall 1622), or the left ventricle is large (i.e., having a free wall 1623). In addition, the shape of the catheter allows the pressure sensor 1106 to be placed in the left ventricle to perform relevant measurements for the above-mentioned methods.

[0196] As described above, the catheter 1100 may also be provided with at least one lumen inside the catheter for a guidewire and / or for saline flushing. The guidewire may be used to influence the radius of the catheter 1100 so that the electrodes 1101, 1102, 1103, 1104, 1105 may be properly placed in the left ventricle.

[0197] When passing through a hard guidewire with a soft tip (e.g., a hard support guidewire with a radius of 0.014 inches (0.036 cm)), the distal curve with a larger diameter (curve 3) will extend to a greater extent than all curves with smaller diameters, due to the lower sensitivity of the curve with a larger diameter to maintain its curvature when resisted by stress (in this case, the stress applied by the harder guidewire). In addition, inserting the hard guidewire through the lumen will cause stress to be applied in the catheter, thereby stretching the arc of the catheter. This stress provides a larger stretch in the arc of the larger diameter, and the total amount of stretch is also determined by the stiffness and thickness of the material of the catheter. The softer and / or thinner portion of the catheter provides less resistance to stretching. In this way, the combination of the curve diameter and the material / structure of the curve will determine how the guidewire can be used to extend the reach of the catheter, that is, the distance from the at least one first electrode (proximal electrode group) to the at least one second electrode (distal electrode group). This enables the catheter to adapt to failing hearts of different sizes.

[0198] Thus, the guidewire can increase the diameter of the distal curve (curve 3) and also increase the distance between the proximal and distal electrodes, allowing the catheter to fit a larger heart diameter and enabling electrode contact at two locations for artificial stimulation for resynchronization, such as may be required to perform one or more of the methods mentioned above. This effect can be achieved in Fig.17 , which shows how the shape of the catheter changes as a stiffer guidewire is passed through the lumen.

[0199] As shown in the figure, when inserting hard guide wire, curve will extend (that is, diameter increases), and softer distal top will straighten, thereby allow guide wire to advance through the top of conduit and advance along vascular system.Then, once conduit is positioned in aortic arch, the retraction of guide wire allows distal top to return to its shape (that is, the shape of curve 4), this stops distal top from entering in the lesser arterial branches of aortic arch and ascending aorta, and the overall curvature of the remainder of conduit 1100 allows conduit to pass through aortic arch and enter in descending aorta when being pushed.Then, when engaging with aortic valve, curved conduit top will pass valve, or move upwards along aortic wall to position larger curve towards valve.At this moment, conduit can be rotated to fit the opening of aortic valve, thereby it is pushed into left heart chamber.

[0200] Fig.18 More details of the catheter are shown, which is shown in a preset configuration (i.e., straight before bending). It can be seen that a y-shaped connector 1810 is provided at the proximal end 110 of the catheter 1100, through which the pressure sensor line 10 and the electrode line 9 extend. In a configuration with 5 electrodes, 5 separate electrode lines can be provided. Each electrode line can be welded to each marker band (i.e., the "electrode" itself).

[0201] The catheter can be provided with lumens 1801, 1802 and 1803. As can be seen, there can be two lumens 1803. The lumens can be provided for any purpose. For example, lumen 1801 can have a diameter of 0.027 inches (0.069 cm) and can be configured for saline flushing. Lumen 1802 can have a diameter of 0.024 inches (0.061 cm) and can be configured so that a rigid guide wire can be provided passing through it. The remaining lumens 1803 can have a diameter of 0.016 inches (0.041 cm) and are suitable for electrode wires 9 and pressure sensor wires 10 to pass through.

[0202] Fig.18 Also shown is region E, which may be suitable for accommodating a pressure sensor. Region E may be a cutout on the surface of the catheter 110 having a depth of 0.014 inches (0.036 cm) and a width between 0.09 inches (0.23 cm) at the surface and 0.075 inches (0.191 cm) at the bottom. Fig.18 In the example of , the cutout is positioned relatively close to the proximal end, but it should be understood that the cutout may be placed closer to the distal end or at the distal end to facilitate manufacturing, and thus the pressure sensor is placed closer to the distal end.

[0203] At the proximal end 1110, the catheter may be coated with a braided wire 6, thereby providing a stronger catheter wire.

[0204] Fig.19 An exemplary system 1900 that allows for processing of signals received from the catheter described above is shown in Figure 7 system shown, or as Figure 7 The catheter can be connected to an amplifier 1901 to amplify the signals received by the catheter. A junction box 1902 combines the electrode signals, pressure signals, and power into a single cable 1903, which can then be attached to a data processing module 1904 (such as a PaCRTool data processing module), which can be configured to acquire data measured by the various electrodes / sensors of the catheter 1100 and perform one or more of the methods described above.

Claims

1. A catheter for evaluating cardiac function, the catheter comprising An elongated shaft extending from a proximal end to a distal end, the shaft having a first curve, a second curve, a third curve, and a fourth curve, the shaft comprising: at least one lumen for receiving a guidewire and / or for saline flushing; at least one first electrode disposed on said second curve of said shaft and configured to contact the septal wall of the left ventricle of a patient in use, said at least one first electrode being used to sense electrical signals and apply pacing to the patient's heart; at least one second electrode disposed on the third curve of the shaft and configured to contact a free wall of the left ventricle of the patient in use, the at least one second electrode being used to sense electrical signals and apply pacing to the patient's heart, the third curve of the shaft having a larger diameter than the second curve of the shaft; at least one sensor disposed on the shaft for detecting an event associated with a rapid increase in the rate of increase of pressure within the left ventricle of the patient; as well as A communication device is configured to transmit data received from the electrodes and the sensor. 2 . The catheter of claim 1 , wherein the at least one sensor comprises a pressure sensor, a piezoelectric sensor, a fiber optic sensor and / or an accelerometer.

3. The catheter of claim 1 or 2, wherein the stiffness of the elongated shaft varies along its length between the proximal end and the distal end.

4. A catheter according to claim 3, wherein the elongated shaft is provided with a rigid proximal end, a moderately rigid middle portion and a flexible tip at the distal end, and optionally wherein The elongated shaft comprises a multi-lumen extrusion having a first cap around the proximal end, a second cap around the intermediate portion, and a third cap around the distal end, the first cap, the second cap, and the third cap having different stiffnesses, and further optionally Wherein the multi-lumen extrusion comprises Pebax 63D, the first cap comprises Nylon 11 or 12 and optionally braided wire, the second cap comprises Pebax 35D, and the third cap comprises Pebax 75D or Pebax 55D.

5. A catheter according to any preceding claim, wherein the electrodes are arranged along the axis so that, in use, at least two electrodes can be positioned relative to each other in the patient's heart.

6. The catheter of claim 5, wherein at least one electrode is configured to be placed in contact with the septal wall of the patient, and at least one electrode is configured to be placed in contact with the contralateral wall of the patient.

7. A catheter according to the preceding claim, wherein the first curve is a counterclockwise curve having a first diameter, the second curve is a clockwise curve having a second diameter, the third curve is a clockwise curve having a third diameter, and the fourth curve is a clockwise curve having a fourth diameter, and preferably, wherein the fourth diameter is smaller than the first diameter, the first diameter is smaller than the second diameter, and the second diameter is smaller than the third diameter.

8. The catheter according to claim 7, wherein the first curve is an arc having an angle of 39°±15%, the second curve is an arc having an angle of 114.5°±15%, and the third curve is an arc having an angle of 76.4°±15%.

9. The catheter of any one of claims 7 or 8, wherein the first diameter is 5 cm ± 15%, the second diameter is 6 cm ± 15%, the third diameter is 7.5 cm ± 15%, and the fourth diameter is 1.5 cm ± 15%.

10. A catheter according to any preceding claim, wherein the catheter is provided with a first thickness of the catheter towards the proximal end, a second thickness and a third thickness at the distal end, wherein the first thickness is greater than the second thickness and the second thickness is greater than the third thickness, and preferably, wherein the first thickness is a diameter of 6Fr, the second thickness is a diameter of 5Fr, and the third thickness is a diameter of 3.5Fr.

11. The catheter of any preceding claim, wherein the at least one first electrode comprises two electrodes disposed on the second curve.

12. The catheter of any preceding claim, wherein the at least one second electrode comprises at least one electrode located on the third curve and at least one electrode located on the fourth curve.

13. The catheter of claim 12, wherein the at least one second electrode comprises at least two electrodes located on the third curve.

14. The catheter of any preceding claim, wherein the at least one sensor is disposed on the second curve.

15. A system comprising A catheter according to any preceding claim; Signal amplifier; Stimulator; and Data processing module; The catheter is configured to be in signal communication with the stimulator, the amplifier and the data processing module, so that the electrodes and the sensors can provide sensing data to the data processing module for further processing, and the electrodes can provide pacing for the patient's heart.

16. The system of claim 15, wherein the data processing module is configured to determine a characteristic response associated with the onset of myocardial synergy from an event associated with a rapid increase in the rate of increase of pressure within the patient's left ventricle.

17. A system according to claim 16, wherein the sensor is configured to provide data about the pressure within the heart to the data processing module, and wherein the data processing module is configured to filter the pressure data to identify the characteristic response associated with the initiation of myocardial synergy, and preferably, wherein the characteristic response includes the beginning of a pressure rise above a pressure floor limit in the pressure signal filtered above a first harmonic of the pressure signal.

18. A system according to claim 17, wherein the characteristic response includes the presence of high frequency components (above 40 Hz) of the pressure signal, and / or wherein the characteristic response includes zero crossings of a bandpass filtered pressure trace.

19. The system of any one of claims 16 or 17, wherein the sensor is configured to provide acceleration data from within the heart to the data processing module, and wherein the data processing module is configured to filter the acceleration data to identify a characteristic response associated with the onset of myocardial synergy; and preferably wherein the data processing module is configured to calculate a continuous wavelet transform of the acceleration data to identify characteristic responses associated with the onset of myocardial synergy, and more preferably wherein the data processing module is configured to calculate the central frequency of the continuous wavelet transform, wherein the characteristic response is the peak value of the central frequency, and more preferably The data processing module is configured to average the central frequencies of multiple cardiac cycles.

20. The system according to any one of claims 16 to 19, wherein the data processing module is configured to identify reversible cardiac dyssynchrony by identifying a shortening of the delay in the onset of myocardial synergy due to pacing, preferably wherein the data processing module is configured to identify a reversible cardiac dyssynchrony in a patient by identifying the characteristic response in the data received from the one or more sensors, using the at least one sensor to measure the timing of an event associated with a rapid increase in the rate of increase of pressure within the left ventricle of the patient, the event associated with the rapid increase in the rate of increase of pressure within the left ventricle being identifiable in each contraction of the heart, the data processing module being configured to measure the timing of the event associated with the rapid increase in the rate of increase of pressure within the left ventricle by: processing signals from the at least one sensor to determine a first time delay between a measured time of an identified characteristic response associated with the rapid increase in the rate of pressure increase within the left ventricle and a first reference time; comparing the first time delay between a measured time of the identified characteristic response associated with the rapid increase in the rate of pressure increase within the left ventricle and the first reference time to a duration of electrical activation of the heart; identifying the presence of cardiac dyssynchrony in the patient if the first time delay is longer than a set fraction of electrical activation of the heart; after applying pacing to the heart of the patient via at least one electrode and / or other electrodes; Calculating a second time delay between the identified characteristic response associated with the rapid increase in the rate of increase of pressure within the left ventricle after pacing and a second reference time after pacing by: measuring, using the at least one sensor, a timing of an identified characteristic response associated with the rapid increase in the rate of increase of pressure within the left ventricle following pacing; as well as processing signals from the at least one sensor to determine the second time delay between a determined time of an identified characteristic response associated with a rapid increase in the rate of increase of pressure within the left ventricle and the second reference time after pacing; comparing the first time delay to the second time delay; and If the second time delay is shorter than the first time delay, a shortening of the delay to the onset of OoS of myocardial synergy is identified, indicating that the time period until the point at which all segments of the heart begin to actively or passively stiffen has been shortened, thereby identifying the presence of reversible cardiac dyssynchrony in the patient.

21. The system of claim 20, wherein the data processing module is further configured to identify the absence of cardiac dyssynchrony in the patient if the first time delay is shorter than a set fraction of electrical activation of the heart; and / or If the first time delay is shorter than a set delay, such as 120 ms, then it is identified that no cardiac dyssynchrony is present in the patient.

22. A system according to any one of claims 15 to 21, wherein the data processing module is configured to determine the extent of concurrent activation of the heart being paced, preferably wherein the data processing module is configured to determine the degree of concurrent activation of a heart being paced via a method comprising: Calculate VCG or ECG waveforms from the right ventricular pacemaker RVp and the left ventricular pacemaker LVp; generating a synthesized biventricular pacing (BIVP) waveform pacing by summing the VCG of the RVp and the LVp, or by summing the ECG of the RVp and the LVp; Calculate the corresponding ECG or VCG waveform from the true BIVP; Comparing the synthesized BIVP waveform with the real BIVP waveform; Fusion time was calculated by determining the time point at which activations from the RVp and LVp met and the synthetic and true BIVP curves began to diverge; in The delay in fusion time indicates that a greater amount of tissue is activated before the electrically activated wavefronts meet, indicating a higher degree of parallel activation.

23. A system according to any one of claims 15 to 22, wherein the data processing module is configured to determine an optimal number and position of electrodes for performing cardiac resynchronization therapy on the heart of the patient based on nodes of a 3D mesh of at least a portion of the heart when the calculated degree of parallel activation of the myocardium is above a predetermined threshold.

24. The system of claim 23, wherein said determining an optimal number and location of electrodes for cardiac resynchronization therapy on a patient's heart is performed via a method comprising: generating the 3D mesh of at least a portion of the heart from a 3D model of at least a portion of the heart of the patient or using a generic 3D model of the heart to obtain the 3D mesh of at least a portion of the heart, the 3D mesh of at least a portion of the heart comprising a plurality of nodes; aligning the 3D mesh of at least a portion of a heart with an image of the heart of the patient; placing additional nodes on the 3D grid corresponding to locations of at least two electrodes on the patient; calculating a propagation velocity of the electrical activation between the nodes of the 3D grid corresponding to the locations of the at least two electrodes; extrapolating the propagation velocity to all the nodes of the 3D grid; calculating the degree of parallel activation of the myocardium for each node of the 3D grid; as well as In the case that the calculated degree of parallel activation of the myocardium is higher than a predetermined threshold, the optimal number and positions of electrodes on the heart of the patient are determined based on the nodes of the 3D grid.

25. A system according to any one of claims 15 to 24, wherein the catheter is configured to be provided into the patient's heart via arterial access, venous access, subclavian access, radial access and / or femoral access, so that the electrodes and sensors in use can be provided within the heart of the patient.

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