CATHETER AND METHOD FOR DETECTING DYSYNERGIA DUE TO DYSYNCHRONY - Patent application

Abstract

A catheter for assessing cardiac function is provided. The catheter comprises an elongate shaft extending from a proximal end to a distal end, the shaft including a guidewire and / or saline irrigation lumen, at least one electrode disposed on the shaft for sensing electrical signals in a bipolar or unipolar manner to pace the patient's heart, at least one sensor disposed on the shaft for detecting events related to a sudden increase in the rate of pressure increase within the patient's left ventricle, and communication means configured to transmit data received from the electrode and the sensor.

Description

[Technical field]

[0001] The present invention relates to catheters, and in particular to catheters that may be utilized in systems and methods for detecting dyssynchrony due to dyssynchrony, for determining the optimal number and location of electrodes for cardiac resynchronization therapy, and / or for measuring time to fusion as a means of determining the degree of parallel activation of the heart. The present invention may thus be used in connection with patients suffering from dyssynchrony heart failure, and more particularly may be applied to identifying patients likely to respond to resynchronization therapy, and optionally to determining the optimal location for placing electrodes to stimulate the heart. The present invention may also be used in patients who have previously suffered from dyssynchrony heart failure. [Background technology]

[0002] Cardiac resynchronization therapy (CRT) is consistently offered to treat patients suffering from a variety of conditions, such as wide QRS complexes, (left or right) bundle branch block, and heart failure, according to accepted medical standards and guidelines provided by international medical societies. There are slight differences between medical guidelines regarding the specific conditions that must occur before CRT is used, such as how wide the QRS complexes are, what type of bundle branch block is occurring, and the degree of heart failure. Summary of the Invention [Problem to be solved by the invention]

[0003] Although CRT is associated with reduced mortality and morbidity, not all patients benefit from this therapy: some may experience a worsening of symptoms after treatment, some may experience devastating complications, and some may experience both.

[0004] In this regard, it would be beneficial to provide a unified strategy to reduce the number of patients who do not respond to CRT and to optimize the treatment of those who may respond, thus increasing the efficacy of this treatment.

[0005] One way to identify such responders may be to detect the onset of synergy after pacing to determine the likelihood of resynchronization of the patient. For example, such methods of determining the onset of synergy are defined in GB1906064.9, PCT / EP2020 / 062149, and each national phase application derived therefrom. Suggested therapies may be suggested by determining the potentially optimal number and location of electrodes, such as by performing measurements to determine the degree of parallel excitation. For example, such methods of determining the degree of parallel excitation are described in GB1906055.7, PCT / EP2020 / 062146, and each national phase application derived therefrom. Certain therapies may indicate the degree of parallel excitation of the heart by validating the effect by calculating the time to wavefront fusion of the electrical wavefronts. For example, such methods of determining the time to fusion in the heart are described in GB1906054.0, PCT / EP2020 / 062152, and each national phase application derived therefrom. Generic catheters for carrying out each of these methods, and detailed descriptions of these methods, are disclosed in GB2016234.3 and PCT / EP2021 / 078365.

[0006] However, it would be desirable to provide a catheter more suitable for carrying out each of the above methods, which may further include a data processing module capable of further processing data received from the catheter to provide a measurement of any of the above values ​​without the need for post-processing of the data. [Means for solving the problem]

[0007] According to a first aspect, the present invention provides a catheter for assessing cardiac function comprising: an elongate shaft extending from a proximal end to a distal end, the elongate shaft having a first curved portion, a second curved portion, a third curved portion and a fourth curved portion, the elongate shaft including a lumen for a guidewire and / or saline flushing; at least one first electrode disposed on the second curved portion of the shaft and configured to contact the septum of a patient's left ventricle in use, the at least one first electrode for sensing electrical signals and applying pacing to the patient's heart; at least one second electrode disposed on the third curved portion of the shaft and configured to contact a free wall of the patient's left ventricle in use, the at least one second electrode for sensing electrical signals and applying pacing to the patient's heart; at least one sensor disposed on the shaft for detecting an event relating to a sudden increase in the rate of pressure rise within the patient's left ventricle; and communication means configured to transmit data received from said electrodes and said sensor, wherein the third curved portion of the shaft has a larger diameter than the second curved portion of the shaft.

[0008] As described below, such catheters may be particularly useful in determining cardiac function, and in particular in providing measurements that indicate whether or not there is dyssynergy in a patient due to electrical excitation caused by dyssynchrony. Once the catheter is properly placed in the left ventricle, with the electrodes facing each other at the septum and the contralateral wall, and the sensor located in the left ventricle, a voltage gradient between each electrode and a reference electrode is recorded for each heartbeat. This voltage gradient represents electrical excitation at the site of the heart where the electrodes are placed. The time course of excitation by the different electrodes determines the degree of dyssynchrony. Further, following the above, the sensor records an event related to the onset of synergy, i.e., a sudden increase in the rate of pressure rise in the left ventricle, which reflects the point in time when all segments of the heart begin to stiffen, either actively or passively. The time to this event is compared to the degree of electrical excitation and dyssynchrony to record the presence of dyssynergy due to dyssynchrony. Although reference is made herein to a sudden increase in pressure in the left ventricle, one skilled in the art will appreciate that such an event may manifest as a more general pressure wave in the patient's heart. Thus, the catheter is not necessarily placed within the patient's left ventricle.

[0009] The heart can then be stimulated from one or more electrodes. For each heartbeat, a voltage gradient between each electrode and a reference electrode is recorded, which can represent electrical activation of the heart as described above. One or more sensors again record events related to the onset of synergy. The temporally more recent events are then compared with the initial events to record the presence or absence of synergy resulting from resynchronization.

[0010] Advantageously, such a system may enable such measurements to be quickly and efficiently determined for various electrode locations, thereby quickly determining not only whether a patient is indeed a potential responder to cardiac resynchronization therapy, but also the ideal number and location of electrodes.

[0011] At least one of the sensors may comprise a pressure sensor, a piezoelectric sensor, a fiber optic sensor, and / or an accelerometer. Such sensors are particularly useful for detecting events related to a sudden increase in the rate of pressure rise in the left ventricle, as described further below.

[0012] The stiffness of the elongate shaft may vary along its length between the proximal and distal ends. In this manner, the elongate shaft may have an ideal configuration for safe, quick and easy positioning within a patient's heart. Optionally, the elongate shaft may have a stiff proximal end, a medium stiffness middle section and a flexible tip at the distal end. This configuration also allows for easy and safe manipulation of the catheter within the heart.

[0013] To provide such differential stiffness along its length, the elongated shaft may be made of a multi-lumen extrusion having a first cover around the proximal end, a second cover around the middle section, and a third cover around the distal end, the first cover having a different stiffness, the second cover having a different stiffness, and the third cover having a different stiffness. Thus, the elongated shaft may be made of a single extrusion of a single material extending along the length of the entire shaft, the stiffness of the extrusion varying along its length depending on the stiffness of the covers provided around the extrusion at predetermined locations. The multi-lumen extrusion may be made of Pebax 63D, the first cover may be made of nylon 11 or 12 and optionally braided wire, the second cover may be made of Pebax 35D, and the third cover may be made of Pebax 75D or Pebax 55D. Such a shaft may be easier to manufacture than a shaft with a varying composition along the entire shaft.

[0014] 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. Although the curves are described herein as clockwise and counterclockwise to clearly distinguish their directions, it will be understood that they can be reversed. For example, reversing the catheter will cause a previously clockwise curve to become counterclockwise, and vice versa. Thus, a curve defined as "clockwise" does not necessarily have to extend in a clockwise direction, but merely in the opposite direction to a curve defined as "counterclockwise". Thus, more generally, one may say that a "clockwise" curve is a curve in a first direction, and a "counterclockwise" curve is a curve in a second direction opposite the first direction.

[0015] 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.

[0016] The first curved portion may be an arc having an angle of 39°±15%, the second curved portion may be an arc having an angle of 114.5°±15%, and the third curved portion is an arc having an angle of 76.4°±15%.

[0017] 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%.

[0018] The catheter may have a first thickness facing the proximal end, a second thickness, and a third thickness at the distal end. The first thickness may be greater than the second thickness, and the second thickness may be greater than the third thickness. The first thickness may be a diameter of 6 Fr (French), the second thickness may be a diameter of 5-6 Fr, and the third thickness may be a diameter of 3.5-5 Fr. As will be understood, the diameters used to describe the "thickness" of a catheter refer to the outer diameter of the cross section of the catheter, as opposed to the diameters (which refer to the diameter of an arc) used to describe each curved portion of the catheter. By varying the thickness along the length of the catheter in this manner, the positioning of each electrode within the heart may be facilitated.

[0019] The at least one first electrode may comprise two electrodes disposed at the second curved portion, and the at least one second electrode may comprise at least one electrode at the third curved portion and at least one electrode at the fourth curved portion.

[0020] The at least one second electrode may comprise at least two electrodes at the third curved portion. The at least one sensor may be disposed at the second curved portion.

[0021] Thus, each bend in the elongate shaft varies in length between the proximal and distal ends, with an initial counterclockwise bend followed by a larger clockwise bend, with the smallest bend at the tip of the clockwise bend, and the diameter of the segmented bends varies, so that a larger diameter bend segment, in combination with the material (i.e., thickness and / or stiffness), may cause the catheter to bend more than a smaller diameter bend segment. Also, as a guidewire of a given stiffness passes through the lumen of the catheter, stresses induced in the catheter will cause the catheter to stretch in an arc. This stress causes a larger stretch in the larger diameter arc, and the total amount of stretch is also determined by the stiffness and thickness of the catheter material. Softer or thinner sections of the catheter will resist stretching less. Thus, the diameter of the bend, in combination with the material / structure of the bend, determines how the guidewire can be used to extend the reach of the catheter, i.e., to extend the distance from at least one first electrode (proximal electrode group) to at least one second electrode (distal electrode group). In this way, the catheter can accommodate a variety of sizes of hearts suffering from heart failure.

[0022] Additionally, a lumen may be provided to allow a guidewire to pass completely through the catheter, such that the guidewire may be extended further than the catheter and inserted through the mitral valve into the left atrium, with the tip of the guidewire positioned in contact with the left atrial myocardium, and then utilized to apply electrical stimulation pulses through the guidewire for artificial stimulation / pacing of the left atrium. Of course, multiple lumens may be provided within the catheter.

[0023] Furthermore, the combination of differently oriented curves allows for effective transmission of torque from the proximal shaft to the distal curve, improving and making electrode positioning within the left heart easier and safer.

[0024] The at least one electrode may include a plurality of electrodes arranged along the shaft such that, in use, at least two electrodes may be positioned opposite one another within the patient's heart. Optionally, at least one electrode is arranged in contact with the patient's septal wall (and to record biopotentials of the conduction system) while at least one electrode is arranged in contact with the patient's contralateral wall to allow measurement of evidence of a delay in propagation of excitation from the septum to the contralateral wall.

[0025] In a second aspect, there is provided a system comprising the catheter as described above, a signal amplifier, a stimulator, and a data processing module, wherein the catheter is configured to be in signal communication with the stimulator, the amplifier, and the data processing module such that data sensed by the electrodes and the sensor can be provided to the data processing module for further processing, and such that the electrodes can provide pacing to a patient's heart.

[0026] Using this system, one can quickly and easily determine how moving the catheter around the heart and shifting the attached electrodes affects cardiac function, and in particular whether pacing can significantly reduce dyssynchrony and dyssynergia.

[0027] The data processing module is configured to determine a characteristic response associated with the onset of myocardial synergy from an event associated with an abrupt increase in the rate of pressure rise within the patient's left ventricle.

[0028] The sensor may be any type of suitable sensor, or combination of suitable sensors, such as an acceleration sensor, a rotation sensor, a vibration sensor, a pressure sensor, etc. The sensor is configured to provide data regarding pressure in the heart to the data processing module, which is configured to filter the data regarding pressure to identify a characteristic response for the onset of the myocardial synergy. The characteristic response may include the onset of a pressure rise above a pressure floor in the filtered pressure signal above a first harmonic of the pressure signal. The characteristic response may include the presence of high frequency components (above 40 Hz) in the pressure signal. The characteristic response may include a band-pass filtered zero crossing pressure trace. Filtering the pressure trace allows for removing associated noise to more accurately and reliably determine the time point for the onset of myocardial synergy. As will be appreciated, the filtered pressure trace or filtered pressure signal referred to herein may equally refer to a filtered "raw" pressure trace or any filtered derivative of a raw pressure trace.

[0029] Additionally or alternatively, the sensor may be configured to provide acceleration data from within the heart to the data processing module, which may be configured to filter the acceleration data to identify a characteristic response related to the onset of the myocardial synergy. For example, the data processing module may be configured to calculate a continuous wavelet transform of the acceleration data to identify a characteristic response related to the onset of the myocardial synergy. The data processing module may be configured to calculate a center frequency of the continuous wavelet transform, the characteristic response being a peak at the center frequency. The data processing module may be configured to average this center frequency over a number of cardiac cycles. Filtering the acceleration traces may remove associated noise to more accurately and reliably determine the time point related to the onset of myocardial synergy.

[0030] As will be appreciated, there are several other methods that additionally or alternatively allow for determining a characteristic response related to the onset of myocardial synergy, which are provided herein, and the data processing module may be configured to perform one or more of such methods.

[0031] For example, the increase in pressure within the heart (e.g., pressure in the left ventricle) over time for two different stimuli may be compared. For example, the pressure curve resulting from right ventricular pacing may be compared with the pressure curve resulting from biventricular pacing. The pressure rise resulting from the two stimuli is aligned with respect to their stimulation timing, and the pressure level is adjusted to match the diastolic portion of the curve prior to ventricular pacing. The point in time when the pressure curves resulting from the stimuli begin to diverge from each other is then detected, which indicates the start of the stimulus co-motion that results in the fastest pressure rise.

[0032] Thus, the rising portion of the pressure curve resulting from the stimulation resulting in a faster pressure rise following the onset of synergy may be shifted to match the rising portion of the pressure curve of the stimulation resulting in a relatively slower pressure rise. The point in time of the rising portion of the pressure curve of the stimulation resulting in a relatively delayed pressure rise, where said curve follows the onset of synergy of the stimulation resulting in a faster pressure rise, is the onset of synergy in the delayed pressure rise curve. A delay between the two points in time at which the onset of synergy was determined may then be calculated. From such calculations, a recommendation may be made as to which pacing strategy to follow with the implantable pacemaker.

[0033] The above process may be automated for data from any number of pacing regimes / stimuli by simple matching of each curve (e.g., using least squares to fit a template to the pressure trajectory) or by comparison of mathematical expressions representing each curve. In this way, it may be possible to reach similar conclusions by analyzing the raw data without having to explicitly plot pressure curves or visually match the curves.

[0034] In this way, the exponential pressure rise to a peak dP / dt due to the onset of synergy can be automatically detected in the data, an exponential equation that fits the pressure curve can be automatically calculated, and the time at which the exponential equation fits one of multiple curves can be determined.

[0035] Template matching may be performed and the cross-correlation between the time lag between the exponential function and the template matching, or similarly other measurements, may be calculated.

[0036] The above method may be performed using filtered pressure measurements as well.

[0037] Additionally or alternatively, advancement of the onset of synergy may be detected by advancement of the zero crossings of a bandpass filtered (e.g., 4-40 Hz) pressure curve (Tp) comparing stimulation with a particular pacing scheme to stimulation with other types of pacing. Such data may be used to indicate the presence of synergy with a particular pacing scheme, and therefore the desirability of receiving CRT with that pacing scheme.

[0038] The method may include calculating a baseline interval (B) by determining the time interval between intrinsic atrial activation (Ta) and an associated zero crossing in the resulting pressure curve (Tp). A corresponding time interval (Tp1) may be calculated after pacing from the first electrode after Ta at a set pacing interval (PI1), which is shortened until the interval from Ta to Tp is less than B. A corresponding time interval (Tp2) may be calculated after pacing from the second electrode after Ta at a set pacing interval (PI2), which is shortened until the interval from Ta to Tp is less than B. A corresponding time interval (Tp3) may be calculated after pacing from the first and second electrodes after Ta at a set pacing interval (PI3), where PI3 is the same time interval as the shorter of PI1 and PI2. By determining which pacing corresponds to the shortest time interval Tp, a pacing scheme that results in the highest degree of synergy may be identified.

[0039] The data processing module may be configured to identify restorative cardiac dyssynchrony by determining a shortened delay to onset of myocardial synergy as a result of pacing. In particular, the data processing module may be configured to time the event of an abrupt increase in the rate of pressure rise in the left ventricle of the patient and identify restorative cardiac dyssynchrony in the patient by identifying the characteristic response in data received from one or more of the sensors using at least one of the sensors, the event of an abrupt increase in the rate of pressure rise in the left ventricle being identifiable for each cardiac contraction.

[0040] The data processing module may be configured to time an event related to an abrupt increase in the rate of pressure rise in the left ventricle by processing signals from at least one of the sensors, identifying a characteristic response related to the abrupt increase in the rate of pressure rise in the left ventricle and determining a first time delay between a time at which the response was measured and a first reference time, identifying a characteristic response related to the abrupt increase in the rate of pressure rise in the left ventricle and comparing the first time delay between a time at which the response was measured and the first reference time with a duration of cardiac electrical activation, identifying that cardiac dyssynchrony is present in the patient if the first time delay is longer than a set rate of cardiac electrical activation, and determining a time of an abrupt increase in the rate of pressure rise in the left ventricle after pacing using at least one of the sensors after application of pacing to the patient's heart by at least one of the electrodes and / or other electrodes. and determining a timing of said response; calculating a second time delay between a time when a characteristic response of an abrupt increase in the rate of pressure rise in the left ventricle after pacing is identified and measured and a second reference time after pacing by processing signals from at least one of said sensors to identify a characteristic response of an abrupt increase in the rate of pressure rise in the left ventricle after pacing and measure a timing of said response; comparing said first time delay to said second time delay; and identifying that the patient has recoverable cardiac dyssynchrony if said second time delay is shorter than said first time delay by determining a shortened delay to onset of myocardial synergy (OoS), indicating a shortened time interval until the point at which all portions of the heart begin to stiffen, either actively or passively.

[0041] Further, the data processing module may be configured to determine the degree of parallel excitation of the paced heart. Specifically, the data processing module may be configured to determine the degree of parallel excitation of the paced heart by a method including: calculating a vector electrocardiogram (VCG) waveform or an electrocardiogram (ECG) waveform from the right ventricular pacing (RVp) and the left ventricular pacing (LVp), generating a composite biventricular pacing (BIVP) waveform by summing the VCG of the RVp and the LVp or summing the ECG of the RVp and the LVp, calculating a corresponding ECG waveform or a VCG waveform from the actual BIVP, comparing the composite BIVP waveform with the actual BIVP waveform, and calculating a time to fusion by determining when the excitation from the RVp and the LVp meets and the composite BIVP curve and the actual BIVP curve start to diverge, where a delay in time to fusion indicates that a large amount of tissue is excited before the wavefronts of electrical excitation meet, thereby indicating a higher degree of parallel excitation.

[0042] Further, the data processing module is configured to determine an optimal number and positioning of electrodes for delivering cardiac resynchronization therapy to the patient's heart based on nodes in the 3D mesh of at least a portion of the heart where the degree of parallel myocardial excitation is calculated to exceed a predetermined threshold. Specifically, the system may be configured to perform a method for determining an optimal number and location of electrodes for delivering cardiac resynchronization therapy to a patient's heart, the method including: generating a 3D mesh of at least a portion of the patient's heart from a 3D model of at least a portion of the patient's heart or obtaining a 3D mesh of at least a portion of the heart using a generic 3D model of the heart, the 3D mesh of at least a portion of the heart including a plurality of nodes; registering the 3D mesh of at least a portion of the heart to an image of the patient's heart; adding a plurality of nodes on the 3D mesh corresponding to locations of at least two electrodes of the patient; calculating a propagation velocity of electrical excitation between the plurality of nodes of the 3D mesh corresponding to locations of the at least two electrodes; extrapolating the propagation velocity to all nodes of the 3D mesh; calculating a degree of parallel excitation of the myocardium for each node of the 3D mesh; and determining an optimal number and location of electrodes on the patient's heart based on nodes of the 3D mesh where the degree of parallel excitation of the myocardium is calculated to exceed a predetermined threshold.

[0043] The catheter may be configured to be provided into the patient's heart through arterial, venous, subclavian, radial, and / or femoral access such that the electrodes and sensors may be provided into the patient's heart in use. [Brief description of the drawings]

[0044] Some preferred embodiments will now be described, by way of example only, with reference to the accompanying drawings, in which: [Figure 1] 1 shows an example of a catheter. [Diagram 2] 2 shows a detailed view of an example guidewire for use with the catheter of FIG. 1. [Diagram 3] 1 illustrates a method of steering a catheter using a guidewire. [Figure 4] 1 illustrates various access routes for directing catheters to the heart. [Diagram 5] 1 shows a cross section of a catheter. [Figure 6] 1 shows a more detailed view of the catheter structure. [Figure 7] FIG. 1 shows a block diagram of a system that comprises a catheter. [Figure 8] 13 shows an example of an analysis that can be performed on acceleration data to calculate time to onset of synkinesis. [Figure 9] 13 shows example graphs of the derivatives of Ptrue and Preading illustrating the effect of sensor calibration. [Figure 10] An example catheter is shown with some example longitudinal dimensions. [Figure 11A] 1 shows the optimized catheter before and after shape setting. [Figure 11B] 1 shows the catheter structure in more detail. [Figure 12] 1 shows in more detail each bend in the catheter after shape setting and the effect of stress on the catheter shape. [Figure 13] 13 shows in more detail each curve of the catheter after shape setting. [Figure 14] The catheter is shown being introduced through the aortic valve and the coronary ostia. [Figure 15] The distribution of each characteristic across the catheter is shown. [Figure 16] The catheter is shown being inserted into the left ventricle. [Figure 17] 1 shows how the catheter is manipulated using a guidewire. [Figure 18] Further details of the catheter are shown, including cross-sections. [Figure 19]1 shows a system for processing data received by a catheter. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0045] The catheters described herein may be used in such methods to 1) identify the presence of underlying factors that identify patients likely to respond positively (significant potential for resynchronization), 2) identify optimal locations for pacing lead / electrode placement, and 3) verify optimal electrode placement and cardiac resynchronization, both prior to and during treatment of patients with heart failure, possibly due to dyssynchrony, with a resynchronization pacemaker (CRT). Those skilled in the art will recognize that the detailed rationale and methodology of these procedures are described, for example, in the applications referenced above, but one example of how the catheters may be used is briefly described herein.

[0046] Many of the figures described herein show a number of example dimensions and materials, however, it will be understood that these are example measurements and materials and that any suitable measurements and materials may be selected to provide those functions.

[0047] Patients are nowadays recommended for the implantation of a pacemaker for CRT based on international guidelines that define indication criteria. These criteria are based on the inclusion criteria of larger clinical trials and consist of symptoms such as heart failure, reduced ejection fraction (heart function), and a widening of the QRS complex (preferably left bundle branch block) of more than 120-150 ms, among others. However, currently, only 50-70% of patients with one or more indications for treatment with CRT actually respond to the treatment. The reasons for these non-responses are manifold, but lead position, underlying factors (dyssynchrony), scarring and fibrosis, and electrode position are the most important reasons. Improving the detection of underlying factors indicative of dyssynchrony heart failure would allow an improved selection of responders (in terms of diagnostic capabilities) for the optimization of treatment (allowing patient-specific therapy).

[0048] First, standard inclusion criteria should be used to identify and define the underlying factor (resynchronization potential) that determines whether a patient will respond to CRT and whether each patient has the factor, if present, then implantation of a pacemaker for CRT should proceed, but if not, other applicable guidelines should be followed.

[0049] If there is an underlying factor, or even if the underlying factor has not yet been identified, the optimal location for the lead may be found based on a parallelism measurement that takes scar and fibrosis into account. The parallelism measurement is performed using an electrode-equipped guidewire or lead inside the heart (e.g., intravenously or intraventricularly). An optimal location for placing the electrode is then suggested.

[0050] If the lead is in the optimal position according to the optimal position determined taking into account the parallelism measured from each node, a response may be confirmed (either by a direct or indirect measurement indicating the onset of myocardial synergy) or, alternatively, the position may not be adopted.

[0051] If a favorable response is confirmed, a CRT pacemaker should be implanted. If a favorable response is not confirmed, parallel mapping and measurements should be refined before final confirmation. If confirmation of response cannot be achieved, implant should be discontinued and known guidelines for alternative implantation should be followed.

[0052] It is contemplated that all of the methods described above and referred to herein may be used together or individually as well. In this regard, it may be possible to find possible dyssynchrony and resynchronization and confirm resynchronization without selecting an optimal lead location, and similarly, it may be possible to select an optimal lead location without identifying the underlying causes and resynchronization.

[0053] Thus, a system may be provided that includes a connection to electrodes that allows visualization of the signal from the patient and the time interval of the measurements. Alternatively or additionally, a system may be provided that includes sensors and electrodes, allowing visualization of the heart model and calculations based on the shape of the heart model. Both above mentioned systems may be combined in the operating room.

[0054] Implementation of the above systems and methods are further described herein through an example intraoperative implementation.

[0055] First, the patient is brought into the operating room, and sensors and electrodes are fixed to the surface of the patient's body.

[0056] One or more additional sensors may be used to determine the delay to onset of myocardial synergy (OoS), such as one or more of a pressure sensor, a piezoresistive sensor, a fiber optic sensor, an accelerometer, ultrasound, or a microphone. Measurements from these additional sensors may be acquired in real time and processed on the spot. If the delay to onset of myocardial synergy is measured to be short relative to the QRS complex or short in absolute terms (e.g., less than 120 ms or less than 80% of the QRS duration), then a CRT device should not be implanted. If the delay to onset of myocardial synergy is measured to be long relative to the QRS complex or long in absolute terms (e.g., more than 120 ms or more than 80% of the QRS duration), then a CRT device should be implanted.

[0057] Parallelism (degree of parallel excitation of the myocardium) can be determined by using body surface electrodes to collect surface potentials for an ECG back-solving excitation map of the heart as described above to determine propagation velocity and therefore the presence of dyssynchrony. Additionally or alternatively, electrodes implanted within the patient's heart may be used to generate an electrical excitation map to determine the presence of dyssynchrony. If the sensed activation pattern indicates that propagation through the tissue is too slow or if scar tissue is present to allow sufficient parallel excitation, then a CRT device should not be implanted.

[0058] The patient is then prepped and sterile draped. The procedure begins as normal, with the leads being placed in the patient's heart via a skin incision below the left clavicle and puncture of the subclavian vein. The leads are then moved into position in the right atrium and right ventricle.

[0059] Dyssynchrony can then be induced by pacing the right ventricle, but confirmed by measuring the delay in myocardial synergy as described above. A sensor can be placed in the left or right ventricle to determine the delay in onset of myocardial synergy. This would involve performing the same calculations as previously utilized to calculate the delay to onset of myocardial synergy.

[0060] Once the lead is in place, a catheter is inserted into the coronary sinus and a biplanar angiogram is performed to visualize the coronary veins.

[0061] Once the coronary veins are visualized, catheterization can be performed using a thin electrode-tipped guidewire or, for mapping purposes, a catheter with one or more electrodes. The time interval measurements are then used to characterize one or more of the intrinsic excitability, tissue properties, and venous properties. The coronary anatomy is then reconstructed in software, and each measurement is assigned to a location within the heart model relative to the reconstructed coronary sinus.

[0062] This data may then be used to calculate parallelism in a method performed ex vivo and highlight the electrode location with the highest parallelism value. Based on these measurements, the surgeon is advised to position the left ventricular (LV) lead with electrodes in the desired location / vein. A similar recommendation can be given for repositioning the right ventricular (RV) lead. Based on the measurements obtained and their processing, it may be recommended to have other or additional electrodes to achieve higher parallelism. Other electrodes refers to electrode locations other than the available electrode locations (endocardial, surgical access) and additional electrodes refers to the use of multiple electrodes (two or more).

[0063] As a result of the above, the coronary venous branches are viewed in two planes and a suitable vein is selected for placement of the left ventricular lead.

[0064] With the LV electrodes in place, sensors may be used to determine the delay to onset of myocardial synergy when pacing both the RV and LV. Different electrodes may be analyzed by repositioning the LV lead to different positions. Measurement of the delay to myocardial synergy may be performed using one or more of pressure sensors, piezoresistive sensors, fiber optic sensors, accelerometers, ultrasound, or measured bioimpedance (when connected to the RV and LV leads). If the delay to myocardial synergy is not reduced, or at least not reduced to, for example, less than 100% of the measured intrinsic value, or if the bioimpedance measurements show paradoxical movement indicating no resynchronization, the proposed lead position should be discarded. The intrinsic value measured from QRS onset does not include the time from pacing onset to ventricular capture and is therefore by definition shorter than the value measured from stimulation. Thus, the approximation to the time interval measured with intrinsic activation is 110%. In this way, the intrinsic delay from the QRS complex to the onset of synkinesis can be calibrated by adding, for example, 15 ms, to a value reflecting the time from the onset of the pacing spike to electrical tissue capture during artificial pacing.

[0065] The VCG can be reconstructed when pacing the RV, LV, or both, and the time to fusion can be calculated. The time to fusion may be used to confirm the already measured parallelism. For the purposes of inverse modeling, each surface electrode can be used to measure the time to fusion. If there is a discrepancy between the measured time to fusion and the measured parallelism, the cause of such discrepancy should be further investigated.

[0066] At the physician's discretion, LV leads with multiple electrodes may be used. Parallelism can be measured with multiple electrodes, and if found to improve parallelism, the improved parallelism can be confirmed by measuring the delay to onset of myocardial synergy using time to fusion.

[0067] When the lead is in the desired location and the delay to onset of myocardial synergy is less than (e.g.) 110% of the initial intrinsic value and less than (e.g.) 100% of the biventricular paced QRS complex, CRT can be performed and the device generator is connected and implanted in the subcutaneous pocket. If the lead is found to not capture the myocardium or the location is determined to be suboptimal based on scientific empirical data and measured intervals (QLV), the lead is repositioned and retested before connecting the device generator. The skin incision is then sutured closed.

[0068] The above system may be embodied in an overall system with signal amplifiers or analog-to-digital converters (ECG, electrogram, and sensor signals), digital converters (sensor signals), processors (computers), software, connectors to X-ray (either direct communication with a dicom or PACS server, or indirect communication with a frame grabber and angle sensors). At the discretion of the user, systems with different sensors may be used. Furthermore, the system may be used to solve other problems. For example, the system may be used to identify the His region and place a pacing lead in the His bundle, with an additional measurement of the delay to onset of myocardial synergy.

[0069] <System example> Provided herein is a catheter configured to be used to detect dyssynergia caused by dyssynchrony and to aid in selecting patients suitable for treatment. Such a catheter is specifically used in the general manner outlined above to identify whether a patient will respond to CRT, select an ideal pacing regimen, and confirm response to treatment.

[0070] The catheter comprises a cardiac catheter with a lumen for a guidewire and for saline flushing. The catheter comprises one or more sensors. For example, the catheter may comprise sensors for detecting vibration, pressure, acceleration, and electrodes for sensing local and global cardiac electrical signals. The catheter may be placed in the left or right ventricle via venous or arterial access and / or in the coronary veins. The electrodes may be used to sense electrical signals in a bipolar or unipolar manner (relative to a reference electrode on the catheter or to other electrodes connected to the patient's body), and may be used for pacing the heart in various locations. The catheter is connected to a data processing system via a cable or wirelessly. A guidewire may be passed through the lumen of the catheter to expand the diameter of the distal curve, or the guidewire may be passed through the end of the lumen and contacted with cardiac tissue for use as a sensing and pacing electrode.

[0071] Once the catheter is inserted into the heart chamber, the electrogram provided by the sensor of the catheter can be used to measure the electrical delay from one electrode to another electrode (or an electrode external to the catheter) and thereby determine the electrical activation time. Additionally, the catheter can be used to measure other factors such as vibration, pressure, acceleration, etc., and filter the signal to receive measurements that can be used to determine the onset of cardiac synergy. Thus, the catheter can also be used to obtain measurements that can be used to measure the degree of resynchronization and the likelihood of resynchronization. Similarly, the catheter can be provided as part of a system that can measure all the data necessary to calculate the time to onset of synergy for a given set of electrode locations. Thus, a system including the catheter can be used to quickly and easily determine the likelihood of resynchronization in a patient.

[0072] Such a catheter may have several uses. As discussed above, the catheter may be used to obtain measurements to be used to detect the onset of synergy after pacing to determine the likelihood of resynchronization in a patient. For example, such methods of determining the onset of synergy are described above, or in GB1906064.9, PCT / EP2020 / 062149, and national phase applications derived therefrom. The catheter may have use in obtaining measurements to determine the extent of parallel excitation. For example, such methods of determining the extent of parallel excitation are described above, or in GB1906055.7, PCT / EP2020 / 062146, and national phase applications derived therefrom. Similarly, the catheter may be utilized to obtain measurements to determine the time to fusion in the heart. For example, such methods of determining the time to fusion in the heart are described above, or in GB1906054.0, PCT / EP2020 / 062152, and national phase applications derived therefrom. The catheter may additionally be provided with a data processing module capable of further processing the data received from the catheter to provide a measurement of any of the above values ​​without the need for post-processing of the data.

[0073] Such a catheter 2600 can be seen in Figure 1. The catheter comprises one or more electrodes 2601, one or more sensors 2602, a shaft 2603, communication means 2604 and 2605, a hemostatic valve 2606, and a guidewire 2607. The catheter extends to a distal end 2608.

[0074] The sensor may be any sensor. For example, if the catheter is used to determine the delay to onset of myocardial synergy, the sensor will likely be a pressure sensor capable of measuring changes in pressure within the left ventricle by invasively measuring pressure within the heart. Additionally or alternatively, the sensor may comprise a piezoelectric sensor, a fiber optic sensor, and / or an acceleration sensor. The sensor may detect and transmit events such as cardiac contractions, onset of synergy, valvular events, pressure, etc. to a receiver connected to a processor.

[0075] The distal end 2608 of the catheter 2600 is a flexible pigtail that allows the electrode 2601 at its curved distal end to be moved by advancing a relatively stiff guidewire 2607 along the shaft of the catheter. Advancing a guidewire through the catheter 2600 expands the diameter of the curve at the distal end 2608 of the catheter 2600. In this way, the distal end 2608 of the catheter 2600 can be moved, thereby moving the electrode 2601. Such variable positions are indicated by the dashed lines 2611 in FIG. 1. Additionally, the distal end 2608 of the catheter 2600 can be provided with a soft tip for atraumatic contact with the sidewall endocardium.

[0076] Communication means 2604 may transmit data received from electrode 2601, and communication means 2605 may transmit data from sensor 2602. As shown, these may be provided as physical wires connecting to an external data processing module. Alternatively, wireless transmission may be provided to transmit data without a physical connection. The shaft of catheter 2600 may have any suitable diameter. For example, the shaft may be a 6Fr shaft. Additionally, saline irrigation may be provided via hemostasis valve 2606.

[0077] A more detailed view of guidewire 2607 can be seen in Figure 2. Guidewire 2607 has a stiffer body 2701 at its proximal end and a flexible tip 2702 at its distal end. This arrangement allows for greater control over the position of the catheter and any electrodes and sensors placed thereon.

[0078] FIG. 3 illustrates how a guidewire 2607 may be used to manipulate the catheter 2600, and more specifically the electrodes and sensors disposed thereon. As shown, the guidewire 2607 is introduced at 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 in a flexible pigtail configuration, and advancing the relatively stiff guidewire 2607 through the catheter 2600 increases the diameter of the curve that the catheter 2600 provides, as shown in FIG. 3. The stiffer body 2701 near the proximal end of the guidewire 2607 allows the catheter to curve more significantly than the flexible tip 2702. This allows for more precise control over the position of the electrodes 2601 (and other sensors 2602) in the catheter 2600.

[0079] Various locations within the heart where the catheter 2600 may be placed are shown in FIG. 4. For example, the catheter may be provided through location A, which provides arterial access to the heart chamber, or through location B, which provides venous access to the heart chamber. Through location A, the catheter (with its associated sensor and electrodes) passes through the septum 2901 to the contralateral wall 2902, such that the electrodes are located on the septal and contralateral walls. Through location B, the catheter may pass through the coronary sinus ostium 2903 and coronary vein 2904, such that the catheter (and electrodes) pass through the venous system and into the coronary vein. Alternatively, the catheter may be provided through a subclavian, radial, or femoral access. The catheter is configured to be positioned in the left ventricle, with the electrodes facing each other on the septal and contralateral walls, and the sensor disposed within the left ventricle. The electrodes are provided to contact tissue.

[0080] 5 shows two cross sections of the catheter 2600. As mentioned above, the catheter 2600 may be provided in any suitable diameter d, such as, for example, 5 Fr. The catheter 2600 is provided with at least one lumen 3001 through which a guidewire may be passed. Saline irrigation may also be provided through the lumen 3001. This lumen may be provided in any suitable diameter, such as, for example, 0.025 inches. The catheter 2600 further includes some conduits 3002 for electrode leads and some conduits 3003 for sensor leads connected to the on-board sensor 2602.

[0081] A more detailed view of the structure of catheter 2600 is shown in Figure 6. As mentioned above, saline irrigation may be provided through hemostasis valve 2606. Catheter 2600 has a stiff proximal end 3101, a medium stiffness middle section 3102, and a flexible tip 3103 at the distal end of the catheter.

[0082] 7 illustrates a data sensing and processing system 3200 including 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 previously described, the catheter 2600 includes an electrode 2601 and a sensor 2602. Each electrode is in signal communication with the stimulator 3201 and an analog converter 3203 of the amplifier 3202 via a communication means 2604. The sensor 2602 is in signal communication with a receiver and converter 3204, and additionally 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 may be connected to the processor 3206 via a fiber optic cable 3205.

[0083] The processing module 3206 may be configured to obtain 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 may be configured to calculate the delay to onset of synergy, the time to fusion, or the degree of parallelism of the patient's heart.

[0084] 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. The catheter 2600 and processing module 3206 may be configured to use such information to automatically and reliably detect a point in time related to the onset of synergy that is distinct from synergy onset, which occurs sometime between the pre-ejection interval (PEI) and the electromechanical delay (EMD).

[0085] For example, the onset of synergy may be related to a sudden pressure rise resulting from the onset of synergy, but the onset of synergy may be more appropriately and reliably represented by a filtered pressure trace. As will be appreciated by those skilled in the art, a filtered pressure trace may refer to the filtered pressure trace itself, or equally to a derivative pressure trace filtered up to any order of derivative. Thus, the system 3200, and more specifically the piezoelectric sensor 2602 and the processing module 3206 of the catheter 2600, may be configured to detect pressure changes within the heart, optionally calculate the derivative of the pressure changes, and filter the pressure trace to accurately represent the onset of synergy. This may be achieved, for example, by removing the first harmonic of the processed pressure wave with a bandpass filter of 2-40 Hz. The curve has a linear rise starting from the onset of synergy and crossing zero at the peak dP / dt, as described above. For example, band pass 2-40 Hz or 4-40 Hz filtering will remove the low and slow frequencies associated with dyssynergia and the onset of synergy may be seen as the start of the pressure rise that leads to or just before aortic valve opening, i.e. maximum pressure.

[0086] This change in the rate of pressure increase is due to the exponential increase in cross-bridge formation while the tension in the passively stretched segments increases, either because they are depolarized or because the elastic model has reached a near maximum value. The rapid cross-bridge formation with isometric or eccentric contractions results in a high frequency component in the frequency spectrum of the pressure curve, reflecting the onset of synergy. This phase of the cardiac cycle is often seen when filtering LVP using a high pass filter above the first or second harmonic. The characteristic filtered waveform increases approximately linearly from the onset of synergy until the zero crossing and continues to increase linearly until the aortic valve opens. The linearly increasing line reflects the period of synergy, with a zero crossing midway through the phase, which corresponds to the peak dP / dt mentioned above, and the onset of synergy is reflected when this line begins to rise above the base or nadir of the filtered pressure curve. Additionally, the catheter 2600 and processing module 3206 may be configured to utilize the high frequency content (above 40 Hz) of the pressure trace to identify the onset of synkinesis in a mid-range (4-40 Hz) filtered signal, since the high frequency content can identify the onset of the pressure rise before the zero crossing.

[0087] One or more of these time points in the pressure trace (the onset of a linear increase in the bandpass filtered pressure trace, the zero crossing in the bandpass filtered pressure trace, the onset of a high frequency pressure component in the pressure trace) may be utilized by the data processing module 3206 to obtain and filter data from a piezoelectric sensor (or other optical sensor) 2602 of the catheter 2600 to accurately and reliably represent the onset of synergy. Additionally or alternatively, the sensor 2602 may include an accelerometer that collects accelerometer data within the heart and determines the onset of synergy from such data, for example as described above and shown in FIG. 8. The raw acceleration data 301 may be bandpass filtered to generate data 3502 from which a wavelet scalogram 3503 may be generated, which represents a frequency spectrum over time. A center frequency trace fc(t) 3504 is then calculated from the wavelet scalogram, as shown in graph 3504. For each cardiac cycle, by averaging the cycle and extracting the time of peak fc(t), one can determine the time to onset of synergy (Td) as shown in graph 3506. The time to onset of synergy may be measured from any suitable reference time 3507, such as, for example, QRS onset.

[0088] As will be appreciated, any of the measurements described above and discussed herein that find the onset of synergy (or a time point directly related thereto) may be combined to provide a more accurate measurement of the onset of synergy and / or how it changes with treatment. For example, measurements of the onset time or time point related thereto before and after treatment calculated by filtering pressure data may be compared and contrasted with the onset time of synergy calculated using raw intracardiac acceleration data before and after treatment. In this manner, a reduction in the time to onset of synergy (which indicates the presence of restorative cardiac dyssynchrony) may be verified using multiple measurements.

[0089] Thus, by utilizing any of the above measurements, the system may automatically determine how the time to onset of synergy varies for each catheter and therefore electrode location, thus providing instant (or near instant) feedback on the effectiveness of various electrode placements in correcting dyssynchrony and dyssynergy.

[0090] In one example, a zero crossing in the filtered signal or a template match in the filtered signal may be detected within a predefined time window from the reference time as a representation of the onset of synergy. For example, a zero crossing within a ±40 ms time window of the QRSend may be measured (ensuring that the first zero crossing is the zero crossing associated with the same heartbeat). Alternatively, the onset of synergy may be indicated by the timing of the nadir (i.e., the point in time when pressure rises from the lowest value) utilizing high frequency components. As will be appreciated, both of these measurements (and others) are the point in time when all parts of the heart begin to stiffen, either actively or passively, and may represent the onset of synergy. This actually manifests as the beginning of a sudden pressure rise in the heart.

[0091] Although the onset of synergy appears as an increase in pressure in the left ventricle since it is the point at which all parts of the heart begin to stiffen, either actively or passively, it will be appreciated by those skilled in the art that this point can also be measured indirectly at other locations. Thus, in addition to being positioned in the left ventricle, a catheter could be positioned, for example, in the coronary vein or right ventricle to provide similar measurements indicative of the onset of synergy, with appropriate filtering of the signal.

[0092] In summary, it can be said that pressure and / or vibration are measured with a catheter, and then various filters are applied to evaluate these pressures / vibrations, and it is possible to determine whether there is asynchrony while also using the electrical signals detected by the catheter. (For example, as calculated above) A decrease in the delay until the onset of co-contraction indicates the presence of asynchrony, but if the interval is longer when there is a stimulus compared to the baseline (i.e., when there is no stimulus), it means that the possibility of iatrogenesis has been identified. Such a situation should be avoided because it can have an adverse effect on the patient's health.

[0093] Of course, the methods that can be applied by the catheter described herein are not limited to the methods described herein. The catheter of the present invention can provide a wider application to other methods than those for detecting the onset of co-contraction, determining the optimal position and number of electrodes, and measuring the time to fusion.

[0094] <Effect of Sensor Calibration on dP / dt> Advantageously, the sensor of the catheter may not require calibration for time events when using the pressure derivative for measuring the onset of co-contraction.

[0095] Theoretically, the error (offset) and gain of the pressure signal should not affect the results when dP / dt = 0 or when dP / dt is at a peak. When dP / dt = 0 or when dP / dt is at a peak, the derivative of the error becomes zero, so the error has no effect. The gain affects the value and slope of the pressure sensor signal, but does not affect the time when the maximum / minimum of the pressure signal occurs (when dP / dt = 0) or the time when the slope of the pressure signal is maximum / minimum (when dP / dt is at a peak).

[0096] This effect is illustrated by the following simplified example showing that neither the error nor the gain affects a periodic pressure signal.

[0097] For example, if a real pressure signal is characterized by the following equation: Ptrue = sin(60t) And the catheter error was 100 mmHg and the gain was 5 times the actual signal. Then the pressure signal reading would be: Preading=5sin(60t)+100 Even if there is a difference between the actual pressure signal and the read pressure signal, the derivative of both equations with respect to time (t) will be: d(Ptrue) / dt=60cos(60t) d(Preading) / dt=300cos(60t) Although the amplitudes of the two dP / dt equations are different, the time when dP / dt=0 and the time when dP / dt peaks are equal for both equations (t=(2n+1)π / 120 and t=nπ / 60 respectively, where n can be any integer value). This is illustrated in Figure 9, which shows a graph of the derivatives of Ptrue and Preading for the above example. From this example, we can see that both Ptrue and Preading simultaneously reach dP / dt=0 and dP / dt peaks.

[0098] Note that the signal changes due to temperature, drift, and atmospheric pressure are all time dependent, which means that in theory they could have some effect on when dP / dt=0 or when dP / dt peaks. However, the largest difference caused by temperature and drift occurs when the catheter is first introduced into the body, as this is when the sensor goes from a dry state at room temperature to a "wet" state at body temperature. By the time the catheter is deployed / positioned and data analysis begins, the amplitudes and frequencies of the temperature, drift, and atmospheric pressure changes are all minimal compared to the amplitudes and frequencies of the pressures inside the heart. Therefore, without correcting for temperature, drift, and atmospheric pressure changes, their effect on when dP / dt=0 or when dP / dt peaks should be negligible.

[0099] FIG. 10 shows an example of a catheter and some example dimensions in the direction of catheter extension. In order to position the electrode 2601 and the sensor 2602 at a desired location in the heart, the flexible tip may be provided with a small diameter d. The central part of the catheter may be provided with a larger diameter D. As an example, the diameter d may be about 1.5 cm and the diameter D may be about 6 cm. The total length of the catheter may be about 130 cm. The electrode 2601 closest to the tip of the catheter may be 1 mm wide and may be located at a distance w, for example 3 cm, from the tip. The two electrodes located closest to the tip may be located 8 mm apart. The sensor 2602 may be located at a distance x, for example 11 cm, from the tip of the catheter. The electrode 2601 may also be located at a distance y, for example 13 cm, from the tip of the catheter. The electrodes may be located at a distance z, which may also be 8 mm. Of course, the above dimensions are exemplary and other dimensions are contemplated.

[0100] In summary, in the above system, a distal portion of the catheter is adapted to position the electrodes opposite each other within the heart. The distal portion has a region intended to contact cardiac tissue. The distal portion is equipped with one or more electrodes and one or more sensors (such as pressure sensors, piezoelectric sensors, fiber optic sensors, accelerometers, etc.) proximal to the distal end of the catheter. The sensor(s) provide data regarding cardiac contractions, onset of synergy, valve events, and pressure to a receiver connected to a processor. The electrodes are connected to an amplifier connected to the processor. The electrodes are connected to a stimulator. The processor analyzes the received data to determine time points regarding onset of synergy and may use this to determine whether dyssynchrony and dyssynergy are present and further determine whether stimulating the electrodes will reverse the dyssynchrony and dyssynergy.

[0101] When the catheter is properly positioned in the left ventricle, with the electrodes facing each other on the septum and contralateral walls, and the sensor in the ventricle, a voltage gradient between each electrode and the reference electrode is recorded for each heartbeat. This voltage gradient represents electrical excitation of the heart. The sensor then records an event related to the onset of synergy, i.e., a sudden 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 maximally, either actively or passively. By comparing the time to this event with electrical excitation, the presence or absence of dyssynchrony and dyssynergy is recorded.

[0102] The heart can then be stimulated from one or more electrodes. The voltage gradient between each electrode and the reference electrode is recorded for each heartbeat, which may represent electrical activation of the heart as described above. The one or more sensors again record events related to the onset of synergy. The temporally more recent events are then compared to the initial events, and the presence or absence of resynchronization is recorded.

[0103] Advantageously, such a system may enable such measurements to be quickly and efficiently determined for various electrode locations, thereby allowing not only to determine whether a patient is indeed likely to respond to cardiac resynchronization therapy, but also to quickly determine the ideal number and location of electrodes.

[0104] <Optimized system> In view of the above, optimized catheters and systems have been developed to allow for more convenient and precise placement of electrodes and various sensors within the heart to more accurately determine various measurements, such as measurements of the onset of synergy.

[0105] As used herein, a curve may be described as having a radius or diameter. Such a curve may be defined by an arc having a given radius or diameter. Thus, it will be understood that when a curve is described as having a radius or diameter, such radius / diameter may be considered to refer to the corresponding radius / diameter of a circle that may define the curve. It will also be understood that any angle and radius / diameter referred to may refer to the angle / diameter of the curve of the "set" catheter, which may change in use under external stress. Furthermore, although each curve is described herein as clockwise and counterclockwise to clearly distinguish their direction, it will be understood that they may be reversed. For example, reversing the catheter will cause a previously clockwise curve to become counterclockwise, and vice versa. Thus, a curve defined as "clockwise" does not necessarily extend in a clockwise direction, but is merely a curve in the opposite direction to a curve defined as "counterclockwise". It will also be noted that while the figures include various dimensions, these are not limiting and may vary.

[0106] Such a catheter 1100 may have a configuration as shown in Figure 11A, which shows the pre-shape setting and post-shape setting configurations of the catheter 1100 (i.e., fully straight, maximum length, and end use configurations). Some example dimensions of the catheter 1100 are additionally shown in Figure 11A. As can be seen, the catheter has a total length of about 110 cm when fully straight, and has the dimensions and spacing between features as shown in Figure 11A. The catheter 1100 extends from a proximal end 1110 to a distal end 1120.

[0107] The catheter has three sections 1121, 1122, 1123, each having a different stiffness. The proximal section 1121, closest to the proximal end 1110 of the catheter, may be the stiffest (e.g., made of nylon 11 or 12, or materials typically used for intracardiac angiography catheters such as polyamide, polyurethane, Teflon, and combinations thereof), and the distal section 1123 at the distal end 1120 may be the most flexible (e.g., made of Pebax 35D). The middle section 1122 has a stiffness intermediate between the other two sections (e.g., made of Pebax 75D or Pebax 55D). The distal section 1123 may extend approximately 4 cm from the distal end 1120 of the catheter 1100. The middle section 1122 may extend approximately 12 cm from the distal section 1123. The proximal section 1121 may extend the remaining length of the catheter, e.g., approximately 94 cm.

[0108] As shown in FIG. 11B, the catheter may include a central extrusion 1131 extending throughout the three sections 1121, 1122, 1123 to provide such variable stiffness. The central extrusion 1131 may have one or more lumens extending therethrough. In the example of FIG. 11B, the central extrusion 1131 is a multi-lumen extrusion. The central extrusion may then be covered with one or more covers or jackets 1132 of different materials in each section to provide different relative stiffness between each section 1121, 1122, 1123. For example, the central extrusion 1131 may be made of Pebax 63D, the harder Pebax 75D, or the softer Pebax 55D, and may be the same material throughout. To provide a stiff proximal end 1121, the central extrusion at the proximal end may be stiffened by providing a jacket of a relatively stiff material, such as nylon 11 or 12, with or without braided wire, around the proximal end of the catheter. The intermediate section 1122 may then be covered with a jacket of a relatively less stiff material, such as Pebax 75D or Pebax 55D, than the jacket at the proximal end. Finally, the flexible tip 1123 may be covered with an even less stiff material, such as Pebax 35D. Providing such a common central extrusion throughout the catheter and varying stiffness with outer jackets of different stiffness may facilitate the manufacture of the catheter. As seen in FIG. 11B, one or more of the materials of the catheter may include a portion of barium sulfate (BaSO4). For example, the material of one or more of the jackets surrounding the proximal section 1121, intermediate section 1122, or distal section 1123 may include 20% BaSC4.

[0109] As shown in FIG. 11A, the catheter 1100 may include five electrodes 1101, 1102, 1103, 1104, and 1105. The five electrodes may be divided into two groups, with three electrodes 1105, 1104, and 1103 located relatively close to the distal end 1120 of the catheter, and the remaining two electrodes 1102, 1101 located farther from the distal end 1120 of the catheter. The inter-electrode distance between the two electrode groups may be selected such that at least one electrode of the electrode group located farther from the distal end contacts the septum, while at least one electrode of the electrode group located closer to the distal end contacts the free wall. Additionally, the spacing between each distal electrode may be narrower than shown. By narrowing the spacing between at least one pair of distal electrodes, bipolar sensing may be achieved, improving spatial resolution to eliminate far-field sensing. This ensures that the signals received by each electrode can be used to detect local electrical activation and thus accurately estimate the electrical delay from baseline (QRS onset) to that region.

[0110] For example, the Euclidean distance between the two pairs of electrodes is approximately 6.5 cm, but can be increased to up to 9 cm by inserting a stiff guidewire into the lumen within the catheter.

[0111] Once the guidewire is inserted into the lumen of the catheter and the catheter is properly positioned within the heart, as seen throughout the figures, the tip of the catheter will point towards the left atrium so that the guidewire can be advanced through the catheter. In this manner, the guidewire can pass through the catheter, through the mitral valve and into the left atrium. Once the tip of the guidewire is placed in contact with the left atrial myocardium, a stimulator can be connected to the proximal end of the guidewire and electrical stimulation pulses can be applied through the guidewire to artificially stimulate / pace the left atrium.

[0112] As an example, the electrode 1105 may be located approximately 3 cm from the distal end 1120 of the catheter 1100, and thus in the distal section 1123, as measured on the catheter prior to shape setting. The electrode 1104 may be located approximately 4 cm from the distal end 1120. Thus, the electrode 1104 may be located either in the distal section 1123, in the middle section 1122, or between the distal section 1123 and the middle section 1122. The electrode 1103 may be located approximately 5 cm from the distal end 1120, and thus in the middle section 1122. These electrodes 1105, 1104, and 1103 may form a first electrode group, and are located closer to the distal end of the catheter 1100 than the second electrode groups 1102, 1101. Of course, the first and second electrode groups may consist of more or fewer electrodes.

[0113] A pressure sensor 1106 is disposed between the first and second electrode groups and may be located approximately 11 cm from the distal end 1120 of the catheter 1100. Alternatively, the pressure sensor 1106 may be located near or at the distal end of the catheter for ease of manufacturing.

[0114] Electrode 1102 is positioned approximately 13.5 cm from the distal end 1120 of catheter 1100 and electrode 1101 is positioned approximately 15 cm from the distal end of catheter 1100, such that both electrodes may be located in intermediate section 1122.

[0115] The catheter may then be set into the desired shape, which is best seen in FIG. 12. The catheter 1100 may be described with reference to four segmented curves: curve 1, curve 2, curve 3, and curve 4. Beginning at the proximal end 1110, the catheter, once set, may be curved counterclockwise to form curve 1, which has a relatively small diameter (typically in the range of 4 cm to 6 cm). The catheter 1100 may then be curved 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, but at a larger diameter (typically in the range of 7 cm to 9 cm), to form curve 3. The catheter 1100 may then be curved in a final tight clockwise curve to form curve 4, which has a smaller diameter (typically in the range of 1 cm to 3 cm).

[0116] 12, when a catheter is introduced into a patient, for example, through arterial, venous, subclavian, radial, and / or femoral access, forces may be exerted on the shaft of catheter 1100. For example, if the catheter is introduced between parallel walls, it may contact these walls at curves 2 and 3, although it could also contact these walls at curve 4. The resulting force causes the larger diameter section (i.e., curve 3) to be pushed inward.

[0117] FIG. 13 shows each curve of the catheter 1100 in more detail and more clearly shows how each curve relates to an arc of a circle having a given radius / diameter. As briefly explained above, the first curve (curve 1) closest to the proximal end 1110 curves counterclockwise to form an arc of about 39°±15% of a circle with a radius of about 2.5 cm±15%. The catheter then curves clockwise (curve 2) to form an arc of about 114.6°±15% of a circle with a radius of about 3 cm±15%. The curve then continues to another curve (curve 3) in the same clockwise direction but with a larger radius of about 76.4°±15% of a circle with a radius of about 3.75 cm±15%. Finally, the catheter 1100 ends with a final curve (curve 4) that is clockwise with a radius of about 0.75 cm±15%.

[0118] As can be seen from Fig. 14, such a curve setting allows the catheter 1100 to easily pass through, for example, the aortic valve. This can be accomplished without curving the distal end to engage the coronary ostium, or instead, the larger curve (i.e., curve 3 above) can be rotated by the operator as it travels along the wall of the ascending aorta, opposed by stress (as shown and described above), to pass through the valve between the leaflets and into the left heart chamber as the valve opens. This is particularly beneficial when providing a catheter within the heart to perform the above method, particularly when determining the onset of synergy.

[0119] Specifically, the combination of variable stiffness along the length of the catheter and the presence of one or more lumens through which a guidewire can pass and impart stiffness to the catheter allows for safe and effective placement of the catheter within the left heart.

[0120] First, the catheter may be placed using a wire that has already passed through the aortic valve. Second, the curve of the catheter resembles the curve of the aortic arch. This allows the curved tip of the catheter to be pushed against the blood flow in the aorta (retrograde) so that it engages the aortic valve without entering the coronary arteries, and then (rotates) through the valve into the left heart and lined up with the tricuspid (or bicuspid) valve opening. Third, the tip of the catheter may be pushed antegrade upwards into the ascending aorta to engage the aortic valve, and the larger curve of the catheter may be rotated to align with and pass through the valve opening, as shown in FIG. 14.

[0121] Once in the left ventricle, the stiffness of the catheter and the various diameters of each bend can be manipulated by inserting a stiff guidewire, and the catheter can be rotated to position the electrodes at different diameters within the left ventricle, allowing each electrode to stimulate different, distant sites on the left side of the heart.

[0122] The shape of the catheter also allows for insertion into the coronary vein and its branches. The shape of the catheter conforms to the curvature of the coronary vein, for example, a 0.014 inch (0.36 mm) coronary guidewire may be passed through the catheter when it is in the coronary vein. The guidewire may then be used to insert the catheter into a branch of the coronary vein and then the wire may be utilized to guide the catheter into the branch. The distal electrode may then be used to stimulate the epicardial region of the left heart covered by the catheterized branch, while the proximal electrode may be used to stimulate the atrium. The pressure sensor may then capture an audible signal from the vibration of the heart valves and use this to detect the onset of synkinesis and induce pacing to resynchronize the left heart. For example, pacing may be induced by atrioventricular delay, as may be used using fusion optimized interval techniques, as will be appreciated by those skilled in the art.

[0123] Figure 15 shows the distribution of various properties throughout the optimized catheter from the proximal end 1110 to the distal end 1120. Each property is shown distributed along the length of the catheter. The grid in Figure 15 shows the scale, with each large square representing a 1 cm increment.

[0124] Taking each feature in turn, generally, the catheter may be provided with two colors: a first color extending from the proximal end 1110 and a second color at the distal end.

[0125] Similarly, the catheter may be provided such that the proximal end 1110 is non-radiopaque and only the distal end is radiopaque.

[0126] The catheter may be provided with a first dimension, such as 6 Fr, at the proximal end 1110. The catheter may then decrease to a second dimension, such as 5 Fr, as it extends toward the distal end 1120. Then, at the distal end of the catheter, the catheter may be provided with a third dimension, such as 3.5 Fr. By way of example, as shown in FIG. 15, the third dimension extends approximately 2 cm from the distal end 1120, the second dimension extends approximately 8 cm from the end of the third dimension, and the first dimension extends from the second dimension to the proximal end 1110 of the catheter. This change in catheter diameter (thickness) may aid in the safe, quick and easy placement of the catheter's electrodes within the heart.

[0127] And in the example of Figure 15, in terms of stiffness, there is a braid at the proximal end 1110 of the catheter, which provides a first stiffness. Then, extending about 3 cm, a second stiffness is provided. Extending from the second stiffness is a third stiffness, which extends about 11 cm. Finally, from the end of the third stiffness, a fourth stiffness is provided, which extends about 2 cm to the distal end 1120 of the catheter. Typically, the fourth stiffness is less than the third stiffness, which is less than the second stiffness.

[0128] Finally, the curvature of the catheter is shown in Figure 15. The proximal end 1110 of the shaft has no curvature. Then curve 1 extends over a length (i.e., the circumference of a circle) of about 1.7 cm. Curve 2 extends in the opposite direction from curve 1 for about 6 cm. Curve 3 then extends for about 5 cm, terminating in curve 4 which extends to the distal end of the catheter for about 3 cm. The relative positions of the electrodes and pressure sensors are also shown.

[0129] Although the above sets forth broad ranges of each of the exemplary catheter's characteristics, one of ordinary skill in the art will recognize that the teachings presented herein are not limited to those exact dimensions, and similarly, each of the above distributions of characteristics may be found alone within an exemplary catheter, i.e., the characteristics are not closely related to one another.

[0130] Rather, the combination of a relatively stiff and / or thick material in the area of ​​the initial curves having a relatively small radius (i.e., curves 1 and 2 as identified above) and a relatively soft material in the area of ​​the relatively large curves (i.e., curves 2 through 3 as identified above) improves the performance of the catheter and, in particular, allows for safe, fast, and easy placement of each electrode within the heart, as described above, for example, with reference to FIG. 14. And, by providing a relatively soft and narrow distal end, the distal relatively soft tip can be easily extended as the relatively stiff guidewire is introduced through the lumen to the distal end. This lumen (and associated guidewire) allows for the distal curve diameter to be varied while increasing the separation of the electrode groups, and also increases the reach of the distal electrodes as the guidewire passes through the lumen. Insertion of the guidewire fully extends the distal soft tip, allowing the catheter to be advanced over the guidewire within the artery / vessel. Also, as described above, a guidewire may be extended longer than the catheter so as to pass through the mitral valve and into the left atrium, with the tip of the guidewire placed in contact with the left atrial myocardium, and then utilized to apply electrical stimulation pulses via the guidewire for artificial stimulation / pacing of the left atrium.

[0131] 16 illustrates the insertion of catheter 1100 into the left ventricle having a septum 1610 and a free wall 1620. As can be seen, the catheter geometry ensures that at least one of electrodes 1101, 1102 will contact the septum and at least one of electrodes 1103, 1104, and 1105 will contact the free wall 1620, regardless of whether the ventricle is small, i.e., has a free wall 1621, normal size, i.e., has a free wall 1622, or the left ventricle is large, i.e., has a free wall 1623. The catheter geometry also allows a pressure sensor 1106 to be positioned in the left ventricle so as to obtain relevant measurements for the methods described above.

[0132] As discussed above, the catheter 1100 may also include at least one lumen within the catheter for a guidewire and / or saline flush. The guidewire may be used to adjust the radius of the catheter 1100 to properly position the electrodes 1101, 1102, 1103, 1104, 1105 within the left ventricle.

[0133] When a stiff guidewire with a soft tip is passed through it (e.g., a stiff support guidewire with a diameter of 0.014 inches (0.036 cm)), the larger diameter distal curve (curve 3) will extend further than all of the smaller diameter curves because the larger diameter curves are less able to maintain their curvature when they are subjected to stresses, in this case those imposed by the stiff guidewire. Insertion of the stiff guidewire into the lumen also imposes stresses on the catheter, which causes the catheter arc to expand. This stress causes the larger diameter arcs to expand more, and the amount of expansion is also determined by the stiffness and thickness of the catheter material. Softer and thinner sections of the catheter offer less resistance to expansion. In this way, the combination of the diameter of the curve and the material / structure of the curve determines how the guidewire can be used to extend the reach 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), allowing the catheter to adapt to the heart failure of different sized hearts.

[0134] Thus, the guidewire may have an increased diameter distal curve (curve 3) to allow the catheter to fit larger heart diameters, and may also increase the distance between the proximal and distal electrodes, allowing electrodes to contact at two sites for artificial resynchronization stimulation, such as that required to perform one or more of the methods referenced above. This effect can be seen in Figure 17, which shows how the shape of the catheter changes as the relatively stiff guidewire passes through the lumen.

[0135] As shown, during insertion of the stiff guidewire, the curved portion stretches (expands in diameter) and the soft distal end straightens, allowing the guidewire to pass over the tip of the catheter and advance along the vessel. Once the catheter enters the aortic arch, pulling back the guidewire causes the distal end to return to its original shape (the shape of curved portion 4), preventing the distal end from entering the aortic arch and the smaller arterial branches of the ascending aorta, while the catheter 1100, once pushed, is able to pass through the aortic arch and into the descending aorta thanks to the general curvature of the remaining portion. Once engaged with the aortic valve, the curved catheter tip will either pass through the valve or move up along the aortic wall to position the larger curve toward the valve. At this point, the catheter can be rotated and pushed into the left heart, aligning it with the opening of the aortic valve.

[0136] 18 shows further details of the catheter, shown in its default configuration (i.e., straight, before bending). As can be seen, the proximal end 1110 of the catheter 1100 is provided with a Y-connector 1810 through which the pressure sensor wires 10 and the electrode wires 9 extend. In a five-electrode configuration, five separate electrode wires may be provided. The electrode wires may each be welded to a marker band (i.e., the "electrode" itself).

[0137] The catheter may be provided with lumens 1801, 1802, and 1803. As can be seen, there may be two lumens 1803. Each lumen may be provided for any purpose. For example, lumen 1801 may be 0.027 inches (0.069 cm) in diameter and may be provided for saline flushing. Lumen 1802 may be 0.024 inches (0.061 cm) in diameter and may be provided to allow for the passage of a stiff guidewire. The remaining lumen 1803 may be 0.016 inches (0.041 cm) in diameter and may be suitable for the passage of electrode wires 9 and pressure sensor wires 10.

[0138] Also shown in Figure 18 is area E, which may be suitable for housing a pressure sensor. Area E is a notch in the surface of catheter 1100 that may be 0.014 inches (0.036 cm) deep and range in width from 0.09 inches (0.23 cm) at the surface to 0.075 inches (0.191 cm) at the bottom. In the example of Figure 18, the notch is located relatively close to the proximal end, but it will be understood that for ease of manufacturing, the notch may be located closer to or at the distal end, and thus the pressure sensor may be located closer to the distal end.

[0139] At the proximal end 1110, the catheter may be coated with a braided wire 6 to provide a more robust catheter wire.

[0140] An example of a system 1900 capable of processing signals received from the catheters described above is shown in Figure 19, which may be used in conjunction with or instead of the system shown in Figure 7. The catheter may be connected to an amplifier 1901 to amplify the signals received at the catheter. A breakout box 1902 may combine the electrode signals, pressure signals, and power into a single cable 1903 which may then be connected to a data processing module 1904, such as the PaCRTool data processing module, which may be configured to obtain 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 elongate shaft extending from a proximal end to a distal end, the elongate shaft having a first curve, a second curve, a third curve, and a fourth curve, the elongate shaft including at least one lumen for receiving a guidewire and / or a saline irrigation therein; at least one first electrode disposed on a second curved portion of the shaft and configured in use to contact a septum of a left ventricle of a patient, the at least one first electrode for sensing electrical signals and applying pacing to the patient's heart; at least one second electrode disposed on a third curved portion of the shaft and configured in use to contact a free wall of a left ventricle of the patient, the at least one second electrode for sensing electrical signals and applying pacing to the patient's heart; at least one sensor disposed in the shaft for detecting an event related to a sudden increase in the rate of pressure rise within the patient's left ventricle; and a communication means configured to transmit data received from the electrodes and the sensor; The third curved portion of the shaft has a larger diameter than the second curved portion of the shaft.

1. An electronic device comprising:

2. At least one of the sensors may comprise a pressure sensor, a piezoelectric sensor, a fiber optic sensor, and / or an accelerometer. The catheter according to claim 1 .

3. The stiffness of the elongate shaft varies along its length between the proximal and distal ends. A catheter according to claim 1 or 2.

4. the elongate shaft having a stiff proximal end, a medium stiffness intermediate section, and a flexible tip at the distal end; Optionally, the elongate shaft is comprised of a multi-lumen extrusion having a first cover around the proximal end, a second cover around the middle section, and a third cover around the distal end, the first cover, the second cover, and the third cover having different hardnesses; Optionally, the multi-lumen extrusion is made of Pebax 63D, the first cover is made of nylon 11 or 12 and optionally braided wire, the second cover is made of Pebax 35D, and the third cover is made of Pebax 75D or Pebax 55D. The catheter according to claim 3 .

5. The electrodes are arranged along the shaft such that, in use, at least two electrodes may be positioned opposite each other within the patient's heart. A catheter according to any one of claims 1 to 4.

6. At least one of the electrodes is configured to be placed in contact with a septal wall of the patient; At least one of the electrodes is configured to be placed in contact with a contralateral wall of the patient. The catheter according to claim 5 .

7. the first curved portion is a counterclockwise curved portion having a first diameter, the second curved portion is a clockwise curved portion having a second diameter, the third curved portion is a clockwise curved portion having a third diameter, and the fourth curved portion is a clockwise curved portion having a fourth diameter; 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. A catheter according to any one of claims 1 to 6.

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

9. 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%. A catheter according to claim 7 or 8.

10. the catheter has a first thickness facing the proximal end, a second thickness, and a third thickness at the distal end; The first thickness is greater than the second thickness, and the second thickness is greater than the third thickness, and preferably, the first thickness is a 6 Fr (French) diameter, the second thickness is a 5-6 Fr diameter, and the third thickness is a 3.5-5 Fr diameter. A catheter according to any one of claims 1 to 9.

11. At least one of the first electrodes comprises two electrodes disposed on the second curved portion. A catheter according to any one of claims 1 to 10.

12. The at least one second electrode comprises at least one electrode at the third curved portion and at least one electrode at the fourth curved portion. A catheter according to any one of claims 1 to 11.

13. The at least one second electrode comprises at least two electrodes in the third curved portion. A catheter according to claim 12.

14. At least one of the sensors is disposed on the second curved portion. A catheter according to any one of claims 1 to 13.

15. A catheter according to any one of claims 1 to 14; A signal amplifier; A stimulator; A system comprising: The catheter is configured to be in signal communication with the stimulator, the signal amplifier, and the data processing module such that data sensed by the electrodes and the sensor can be provided to the data processing module for further processing, and such that the electrodes can provide pacing to the patient's heart. A system characterized by:

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

16. The system of claim 15.

17. the sensor is configured to provide data relating to pressure within the heart to the data processing module; the data processing module is configured to filter the pressure related data to identify a characteristic response related to an onset of the myocardial synergy; The characteristic response includes the onset of a pressure rise above a pressure floor in the filtered pressure signal above a first harmonic of the pressure signal.

17. The system of claim 16.

18. the characteristic response includes the presence of high frequency components (above 40 Hz) in the pressure signal; and / or The characteristic response includes a bandpass filtered zero-crossing pressure trace.

20. The system of claim 17.

19. the sensor is configured to provide acceleration data from within the heart to the data processing module; the data processing module is configured to filter the acceleration data to identify a characteristic response related to an onset of the myocardial synergy; Preferably, the data processing module is configured to calculate a continuous wavelet transform of the acceleration data to identify characteristic responses related to the onset of the myocardial synergy; the data processing module is configured to calculate a center frequency of the continuous wavelet transform; the characteristic response being a peak at the center frequency; More preferably, the data processing module is configured to average the central frequency over a number of cardiac cycles.

18. A system according to claim 16 or 17, characterized in that

20. the data processing module is configured to identify restorative cardiac dyssynchrony by determining that a delay to onset of myocardial synchrony is shortened as a result of pacing; Preferably, the data processing module is configured to time the event of an abrupt increase in the rate of pressure rise in the left ventricle of the patient and identify restorative cardiac dyssynchrony in the patient by identifying the characteristic response in data received from one or more of the sensors using at least one of the sensors; said event relating to a rapid increase in the rate of pressure rise within the left ventricle is identifiable with each contraction of the heart; the data processing module is configured to time the event relative to an abrupt increase in the rate of pressure rise in the left ventricle; The identification of the reversible cardiac dyssynchrony comprises: processing signals from at least one of said sensors to identify said characteristic response of an abrupt increase in the rate of pressure rise in the left ventricle and to determine a first time delay between the time at which said response was measured and a first reference time; identifying said characteristic response relating to an abrupt increase in the rate of pressure rise within the left ventricle and comparing said first time delay between said time at which said response was measured and said first reference time with a duration of cardiac electrical activation; identifying the patient as having cardiac dyssynchrony if the first time delay is greater than a set percentage of cardiac electrical activation; identifying, after application of pacing to the patient's heart by at least one of said electrodes and / or other electrodes, using at least one of said sensors to identify said characteristic response of an abrupt increase in the rate of pressure rise in the left ventricle after pacing and measure a timing of said response, and processing signals from at least one of said sensors to determine a second time delay between the time at which the characteristic response of an abrupt increase in the rate of pressure rise in the left ventricle after pacing was determined and a second reference time, thereby calculating a second time delay between the time at which the characteristic response of an abrupt increase in the rate of pressure rise in the left ventricle after pacing was measured and a second reference time after pacing; comparing the first time delay to the second time delay; and identifying the presence of restorative cardiac dyssynchrony in the patient by determining a shortened delay to onset of myocardial synergy (OoS) when the second time delay is shorter than the first time delay, indicating a shortened period of time until all segments of the heart begin to stiffen, either actively or passively.

20. A system according to any one of claims 16 to 19, characterized in that

21. The data processing module further comprises: Identifying that the patient is free of cardiac dyssynchrony if the first time delay is less than a set percentage of cardiac electrical activation; and / or If the first time delay is less than a set delay, for example 120 milliseconds, then the patient is identified as not having cardiac dyssynchrony.

21. The system of claim 20.

22. the data processing module is configured to determine, via a predetermined method, a degree of parallel activation of the paced heart; The method comprises: Calculating a vectorcardiogram (VCG) waveform or an electrocardiogram (ECG) waveform from the right ventricular pacing (RVp) and the left ventricular pacing (LVp); generating a composite biventricular pacing (BIVP) waveform pacing by summing the VCGs of the RVp and the LVp or by summing the ECGs of the RVp and the LVp; Calculating a corresponding ECG or VCG waveform from the actual BIVP; comparing the waveform of the synthetic BIVP with the waveform of the actual BIVP; calculating time to fusion by determining the point at which activation from the RVp and LVp meets and the composite BIVP curve and the actual BIVP curve begin to diverge; The time delay to fusion indicates that a large amount of tissue is excited before the electrical excitation fronts meet, thereby indicating a higher degree of parallel excitation.

22. A system according to any one of claims 15 to 21, characterized in that

23. The data processing module is configured to perform a determination of an optimal number and location of electrodes for delivering cardiac resynchronization therapy to the patient's heart based on nodes of the 3D mesh of at least a portion of the heart where a degree of parallel activation of the myocardium is calculated to exceed a predetermined threshold.

23. A system according to any one of claims 15 to 22, characterized in that

24. The determining of an optimal number and location of electrodes for delivering cardiac resynchronization therapy to the patient's heart is performed in a predetermined manner, the method comprising: generating a 3D mesh of at least a portion of a patient's heart from a 3D model of at least a portion of the heart or obtaining a 3D mesh of at least a portion of the heart using a generic 3D model of the heart, the 3D mesh of at least a portion of the heart including a plurality of nodes; registering the 3D mesh of at least a portion of the heart to an image of the patient's heart; adding a number of nodes onto the 3D mesh corresponding to locations of at least two electrodes on the patient; calculating a propagation velocity of electrical excitation between the plurality of nodes corresponding to the locations of the at least two electrodes in the 3D mesh; extrapolating said propagation speed to all nodes of said 3D mesh; calculating a degree of parallel activation of the myocardium for each node of the 3D mesh; determining an optimal number and location of electrodes on the patient's heart based on nodes of the 3D mesh where the degree of parallel myocardial excitation is calculated to exceed a predetermined threshold.

24. The system of claim 23.

25. The catheter is configured to be provided into the patient's heart through arterial, venous, subclavian, radial and / or femoral access such that the electrodes and sensors may be provided into the patient's heart in use.

25. A system according to any one of claims 15 to 24, characterized in that

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