Phrenic nerve stimulation

Abstract

The present disclosure relates in particular to a system for phrenic nerve stimulation. The stimulation system comprises a catheter (200) including one or more intravascular electrodes, each disposed on a distal portion (240) of the catheter. The catheter is configured to be introduced into the superior vena cava (VC) of a human patient. The stimulation system also comprises an external electrode patch (260) configured to be affixed to the patient on an opposite distal side to the phrenic nerve. The external electrode patch is operable in a bipolar mode with the one or more intravascular electrodes. Such a system forms an improved solution for phrenic nerve stimulation, particularly during cryoablation procedures.

Description

Technical Field

[0001] The present disclosure relates to systems, methods, kits, and computer programs for phrenic nerve stimulation and / or cardiac cryoablation.

Background Art

[0002] Atrial fibrillation is a common arrhythmia. One option for treatment is ablation of atrial fibrillation by a minimally invasive procedure. Atrial fibrillation ablation is a type of cardiac ablation that blocks the errant electrical signals causing the arrhythmia by damaging or destroying the tissue within the heart. For example, one or both pulmonary veins can be isolated by forming a circumferential lesion, such as surrounding the ostium of the pulmonary vein. Among minimally invasive cardiac ablation techniques, cardiac cryoablation is a procedure that has gained support among electrophysiologists. The cryoablation technique is accomplished by electrically isolating the pulmonary veins of the heart by "burning" the tissue using a cryoablation catheter, which is most often a cryoballoon catheter (or a freezing balloon catheter).

[0003] The most common complication of cryoablation technology is right diaphragmatic paralysis caused by damage to the right phrenic nerve due to the proximity of the right phrenic nerve to the pulmonary vein. Such damage does not occur systematically during the cryoablation procedure, but still affects a non-negligible number of patients. And although the damage is mostly recoverable, a relatively large number of patients who have been damaged still have an impact the next day, and in some patients, diaphragmatic paralysis may persist for a relatively long time until spontaneous healing occurs.

[0004] Non-patent document 1 outlines damage to the right phrenic nerve by cryoablation, techniques for mitigating such damage, and problems associated with such techniques. One widely used technique, which is reviewed in this paper, is to perform electrical stimulation of the right phrenic nerve during the cryoablation procedure. Since the phrenic nerve controls the muscle contraction of the right diaphragmatic dome, this technique further includes monitoring the contractile response induced by the electrical stimulation and taking action accordingly.

[0005] Figure 1 illustrates a conventional technique for performing such a phrenic nerve stimulation technique. The figure illustrates the positioning of an electrophysiological catheter 10 for electrical stimulation of the right phrenic nerve PN, with an anatomical cross-section H of the heart on the left and a corresponding medical image I on the right. The stimulation catheter 10 is introduced through the femoral vein, with its distal end 14 positioned within the superior vena cava VC to stimulate the phrenic nerve PN. The stimulation catheter 10 has multiple (e.g., four) electrodes 11 positioned as close as possible to the medial side of the superior vena cava (above the heart) and opposite the phrenic nerve PN at its distal end 14. The stimulation catheter 10 may be a linear quadruple catheter, a commonly used commercially available catheter. The operator positions the electrodes 11 and stimulates the phrenic nerve by activating two electrodes in bipolar mode. The operator observes the contraction of the right diaphragm induced by the electrical stimulation to help assess the possibility of damage to the right phrenic nerve. Such an assessment allows the operator to make clinical decisions to reduce the likelihood of complications.

[0006] This type of electrical stimulation presents several problems. First, the operator must first locate the correct position on the stimulating catheter's electrodes to stimulate the phrenic nerve. If the operator "misjudges" the position, the current supplied by the electrodes will not effectively stimulate the phrenic nerve. Therefore, the operator has the inconvenience of having to ensure the stimulating catheter is in the correct position. Furthermore, even if the operator has confirmed the stimulating catheter is in the correct position before applying electrical stimulation, they must ensure that the stimulating catheter remains in that position during the stimulation to ensure stable electrical stimulation to the phrenic nerve. Maintaining stability of electrical stimulation while using currently available stimulating catheters is a difficult task for the operator. Therefore, the operator may "lose track" the phrenic nerve during electrical stimulation, which leads to unstable electrical stimulation. To correct the stimulation, the operator needs to readjust the catheter's position. This is inconvenient for the operator as it wastes time to readjust the stimulating catheter's position and restart the stimulation. Moreover, this method relies on monitoring the diaphragm to assess phrenic nerve damage. However, if diaphragmatic monitoring becomes unstable and unavailable, the operator will be unable to assess phrenic nerve damage. Furthermore, unstable stimulation can sometimes lead to a decreased diaphragmatic contraction response, which may be misinterpreted as phrenic nerve damage or a precursor to damage. This can cause the operator to make an incorrect judgment, even if the decrease is simply due to catheter displacement. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] “Contemporary analysis of phrenic nerve injuries following cryoballoon-based pulmonary vein isolation: A single-centre experience with the systematic use of compound motor action potential monitoring”,Anwar,O.et.al.,2020 [Overview of the project] [Problems that the invention aims to solve]

[0008] Given this background, there is still a need for methods to improve phrenic nerve stimulation, particularly during cryoablation procedures. [Means for solving the problem]

[0009] A system for phrenic nerve stimulation is provided. This stimulation system comprises a (stimulation) catheter containing one or more intravascular electrodes, each positioned distal to the catheter. The catheter is configured to be introduced into the superior vena cava of a human patient, with its distal end positioned in the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein. The stimulation system also comprises an external electrode patch configured to be attached to the patient on the opposite side of the distal end to the phrenic nerve. The external electrode patch is capable of operating in bipolar mode with one or more intravascular electrodes.

[0010] In the examples, the extracorporeal electrode patch may have a conductive surface having a length of 1 cm or more and / or a width greater than 1 cm. For example, the conductive surface may be greater than 4 cm in length and greater than 2 cm in width, which is, for example, greater than 8 cm in length and greater than 4 cm in width. Optionally, the length of the conductive surface may be less than 40 cm or 30 cm, and / or the width of the conductive surface may be less than 30 cm or 20 cm. For example, the conductive surface may be less than 30 cm in length and less than 20 cm in width. For example, the conductive surface may be about 20 cm in length and about 10 cm in width.

[0011] In the examples, the extracorporeal electrode patch may comprise a conductive layer made of a flexible material and / or a metallic material. For example, the extracorporeal electrode may be made of a flexible metal layer. Additionally, or alternatively, the extracorporeal electrode patch may comprise a conductive adhesive coating.

[0012] In the embodiment, the distal portion of the stimulating catheter may include an expandable portion, and the stimulating catheter may have an expanded form.

[0013] In such embodiments, the expandable portion may preferably be configured to circumferentially conform to the inner walls of the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein so as to remain in place during phrenic nerve stimulation. Additionally or alternatively, one or more intravascular electrodes may be positioned at least partially on the expandable portion. In such cases, optionally, at least one intravascular electrode positioned on the expandable portion may be longer than it is wide and positioned on the expandable portion to extend substantially along the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein when the stimulating catheter is in an expanded state. Furthermore, additionally or alternatively, at least one intravascular electrode may be positioned on the expandable portion to contact the inner walls of the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein when the stimulating catheter is in an expanded state.

[0014] Additionally, or alternatively, in such embodiments, when in an expanded form, one or more intravascular electrodes may be arranged on the circumference of the expandable portion.

[0015] In addition or alternatively, in such embodiments, the extended configuration may be spiral or vortex, loop, lasso, umbrella, or basket-like.

[0016] In addition or alternatively, in such embodiments, the expandable portion may, when in its expanded form, form a helix or spiral consisting of up to two turns of coil.

[0017] In addition, or alternatively, in such embodiments, the catheter may have a non-expandable distal end following the expandable portion.

[0018] Additionally, or alternatively, in such embodiments, the non-expandable distal end may be linear.

[0019] In addition, or alternatively, in such embodiments, the length of the non-expandable distal end may be greater than 1 cm and / or less than 12 cm, for example, between 1.5 cm and 4 cm.

[0020] Additionally, or alternatively, in such embodiments, the diameter of the expandable portion may be between 10 mm and 35 mm when in its expanded form.

[0021] In addition or alternatively, in such embodiments, the stimulating catheter may include one or more pull wires that are operable to deform the stimulating catheter into an expanded form, and / or the expandable portion may be at least partially made of a shape memory material that biases the expandable portion into an expanded form.

[0022] In the embodiment, the catheter may be provided with a lumen for introducing a retractable, linearized inner member.

[0023] In such an embodiment, the catheter may further comprise a straightening inner member within the lumen.

[0024] Additionally or alternatively, in such an embodiment, the straightening inner member may be a guide wire.

[0025] Additionally or alternatively, in such an embodiment, the guide wire may be made of metal, have a diameter greater than 0.020” and / or less than 0.060”, preferably greater than 0.030” and / or less than 0.040”, for example 0.032” or 0.035”, and / or may be made of a hydrophobic material.

[0026] In an embodiment, one or more intravascular electrodes may consist of a plurality of electrodes spaced along the stimulation catheter. In such an embodiment, optionally, the plurality of electrodes may consist of more than 5 electrodes and / or less than 20 electrodes. For example, the plurality of electrodes may consist of about 10 electrodes. Additionally or alternatively, in such an embodiment, the spacing between the plurality of electrodes may be greater than 4 mm and / or less than 18 mm, for example about 9 mm. Further additionally or alternatively, the plurality of electrodes may be connected together to form a monopole.

[0027] In an embodiment, the length of at least one intravascular electrode may be greater than 0.5 mm and / or less than 2.5 cm. Additionally or alternatively, the width of at least one intravascular electrode may be greater than 0.3 mm and / or less than 2.5 mm.

[0028] In the embodiment, the system may further include an energy source configured to electrically conduct to one or more intravascular and extracorporeal electrode patches. For example, the energy source may be configured to deliver, for example, an electrical pulse with a voltage amplitude between 1V and 50V and / or a duration between 0.1ms and 20ms.

[0029] In the embodiment, one or more intravascular electrodes may consist of a plurality of electrodes electrically connected to each other to form a monopole, or they may consist of a plurality of individual electrodes electrically disconnected from each other and capable of functioning as a monopole collectively.

[0030] In the embodiment, one or more intravascular electrodes may consist of multiple electrodes, and the system is configured to operate the multiple electrodes to simultaneously deliver electrical pulses between the individual electrodes of the multiple electrodes and the extracorporeal electrode patch.

[0031] Furthermore, a system for cardiac cryoablation is provided. This cryoablation system comprises a stimulation system and a cryoablation catheter, such as a cryo-balloon catheter.

[0032] Furthermore, a method for stimulating the phrenic nerve is provided. This stimulation method includes the steps of providing a phrenic nerve stimulation system, attaching an external electrode patch to a human patient on the side opposite to the distal end of the phrenic nerve, introducing a stimulation catheter into the patient's superior vena cava, positioning the distal end of the stimulation catheter in the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein, and operating the external electrode patch in bipolar mode with one or more intravascular electrodes to stimulate the phrenic nerve.

[0033] "The area opposite the distal portion of the phrenic nerve" refers to the portion of the patient's skin that roughly lies between the distal portion (i.e., the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein) and the phrenic nerve. More precisely, it refers to the area of ​​the patient's upper body consisting of the back (i.e., the posterior), the right side of the upper body (i.e., between the back and chest, under the right armpit and above the right hip, excluding the right arm and the side of the right shoulder), the upper part of the right shoulder, and the back of the neck. Therefore, the chest, abdomen, and right arm (including the side of the right shoulder) are not included in this area.

[0034] In the embodiment, the extracorporeal patch may be attached to at least a portion (e.g., entirely) of the right half of the patient's back, and / or to at least a portion of the right side of the upper body (excluding the right arm). Additionally, or alternatively, the extracorporeal patch may be positioned such that at least a portion of the patch is substantially at the same height as the distal end of the stimulating catheter, relative to the patient's height (i.e., from the patient's feet to their head). For example, the extracorporeal patch may be attached below the base of the neck, at most substantially up to the base of the neck; below the right shoulder, at most substantially up to the right shoulder; or below the right armpit, at most substantially up to the right armpit. Thus, the extracorporeal patch may face the distal end of the stimulating catheter and / or one or more intravascular electrodes, i.e., a horizontal line may connect them. In other words, the extracorporeal patch may be positioned such that the phrenic nerve is substantially located between the extracorporeal patch and the distal end of the stimulating catheter and / or one or more intravascular electrodes.

[0035] In certain embodiments, the external electrode patch may be attached at least partially to the back in the right paravertebral region, facing the medial portion of the right scapula, and may extend to the base of the neck. Additionally, or alternatively, the external electrode patch may be attached to at least a portion of the right chest region of the patient.

[0036] In the embodiment, the external electrode patch may be applied so that it extends along the patient's back or right side (i.e., its longitudinal direction extends from the patient's feet to their head). Alternatively, the external electrode patch may be applied so that it extends laterally along the patient's back and right side.

[0037] In the embodiment, the stimulation method may further include the step of positioning at least one electrode against a portion of the medial wall of the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein that faces the phrenic nerve.

[0038] In the examples, the stimulation method may further include the step of monitoring the diaphragm's response to phrenic nerve stimulation.

[0039] Furthermore, a cryoablation method is provided. The cryoablation method includes a step of introducing a cryoablation catheter into the left atrium of a human patient, a step of performing cryoablation, and a step of repeating a phrenic nerve stimulation method, which includes a step of monitoring the diaphragmatic response to phrenic nerve stimulation while performing cryoablation. If the diaphragmatic response is reduced, the cryoablation method may further include a step of pausing the cryoablation and then resuming the cryoablation.

[0040] Furthermore, a kit for phrenic nerve stimulation is provided. The kit includes a stimulation system or a cryoablation system. The kit also includes instructions for stimulating the phrenic nerve in a human patient, for example, during cardiac cryoablation, and optionally, instructions for monitoring the diaphragmatic response to phrenic nerve stimulation, and / or instructions for performing cardiac cryoablation.

[0041] Furthermore, a computer program is proposed that includes executable code for operating the energy source of a stimulation system in order to perform a stimulation method, for example. The computer program may be stored in non-volatile memory and cause a processor to operate the energy source to deliver electrical pulses configured, for example, for phrenic nerve stimulation. The stimulation system may include such a processor and / or such non-volatile memory as part of an energy unit, for example, that includes the energy source. The stimulation system may further include the computer program stored in the memory, or alternatively, the computer program may be downloadable from a remote location and the stimulation system may be configured to install the downloaded computer program.

[0042] Embodiments of the present invention will be described below with reference to the accompanying drawings, as non-limiting examples. [Brief explanation of the drawing]

[0043] [Figure 1] This figure shows a conventional technique for phrenic nerve stimulation. [Figure 2] This figure shows an example of a stimulation method using an example of a stimulation system. [Figure 3] This figure shows an example of a cryoablation system. [Figure 4] This figure shows an example of a phrenic nerve stimulation catheter with an expandable portion. [Figure 5A] This is a longitudinal section showing an example of a lasso-shaped catheter for phrenic nerve stimulation. [Figure 5B] This is a cross-sectional view showing an example of a phrenic nerve stimulation catheter with a lasso-like structure. [Figure 6A] This figure shows an example of a spiral-shaped phrenic nerve stimulation catheter in an expanded form. [Figure 6B] This figure shows an example of a spiral-shaped phrenic nerve stimulation catheter in a linear configuration. [Figure 7] An example of a phrenic nerve stimulation catheter with a horizontal loop configuration is shown. [Figure 8] An example of a phrenic nerve stimulation catheter with a vertical loop configuration is shown. [Figure 9] An example of a phrenic nerve stimulation catheter with an umbrella-shaped structure is shown. [Figure 10] An example of a phrenic nerve stimulation catheter with a cage-like structure is shown. [Figure 11] An example of a phrenic nerve stimulation catheter with an expandable portion is shown. [Figure 12] An example of a phrenic nerve stimulation catheter with an expandable portion is shown. [Figure 13] An example of a phrenic nerve stimulator having an expandable portion and a non-expandable distal end is shown. [Figure 14] An example of a phrenic nerve stimulation catheter with an expandable portion is shown. [Figure 15] An example of a phrenic nerve stimulation catheter with an expandable portion is shown. [Figure 16] An example of a phrenic nerve stimulation catheter with an expandable portion is shown. [Figure 17] An example of a phrenic nerve stimulator having an expandable portion and a non-expandable distal end is shown. [Figure 18] An example of a phrenic nerve stimulator having an expandable portion and a non-expandable distal end is shown. [Modes for carrying out the invention]

[0044] In this disclosure, phrenic nerve stimulation or phrenic nerve strictly means the right phrenic nerve. Similarly, when referring to diaphragmatic dome contraction or diaphragm, strictly means the right diaphragm. Furthermore, when referring to “vena cava” without further clarification, strictly means the superior vena cava. Furthermore, when referring to “patient,” strictly means a human patient.

[0045] In this disclosure, the following abbreviations are used for physical units: milliseconds are "ms", seconds are "s", millimeters are "mm", centimeters are "cm", volts are "V", and millivolts are "mV".

[0046] The phrenic nerve stimulation system comprises a stimulation catheter and an external electrode patch configured to be attached to the patient. The stimulation catheter is configured to be introduced into the patient's vena cava such that its distal end is located within the vena cava, the right brachiocephalic vein, and / or the right subclavian vein. The external electrode patch is attached to the patient on the opposite side of the distal end of the stimulation catheter relative to the phrenic nerve. The stimulation catheter comprises one or more intravascular electrodes, each positioned distal to the stimulation catheter. The external electrode patch is capable of operating in bipolar mode with one or more intravascular electrodes.

[0047] Such stimulation systems form a solution for performing an improved method of phrenic nerve stimulation. This stimulation method includes the steps of providing a stimulation system, attaching an external electrode patch to a human patient on the side opposite to the distal end of the phrenic nerve, introducing a stimulation catheter into the patient's superior vena cava, positioning the distal end of the stimulation catheter in the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein, and performing phrenic nerve stimulation by operating the external electrode patch in bipolar mode with one or more intravascular electrodes.

[0048] "Configured to be introduced into the patient's vena cava such that the distal end is located in the vena cava, the right brachiocephalic vein, and / or the right subclavian vein" means that the stimulating catheter is configured such that at least the distal end is introduced into the vena cava, optionally further into the right brachiocephalic vein, and optionally further into the right subclavian vein. The distal end of the stimulating catheter may be positioned and operated within the vena cava. Additionally, or alternatively, the distal end of the stimulating catheter may be positioned and operated within both the vena cava and the right brachiocephalic vein. This may be, for example, selectively or simultaneously, positioned and operated within both vessels (part of the distal end in one vessel and another part in the other). Additionally, or alternatively, the distal end of the stimulating catheter may be positioned and operated within all three vessels: the vena cava, the right brachiocephalic vein, and the right subclavian vein. This may be, for example, positioned and operated within all three vessels and / or within pairs thereof (e.g., pairs of consecutive vessels). "Simultaneously" means that the distal portion may be partially positioned within one blood vessel and simultaneously partially positioned within another. Therefore, the distal portion of the stimulating catheter may be positioned and manipulated within any such blood vessel in the vena cava region near the phrenic nerve. Hereafter, we will refer to the location of such a distal portion of the stimulating catheter as the "blood vessel of the vena cava region."

[0049] When the stimulating catheter is located within a blood vessel in the superior vena cava region of a human patient, an external electrode patch is attached to the patient on the opposite side of the distal end to the phrenic nerve, and the stimulating catheter is operated in bipolar mode using the patch (i.e., the multiple intravascular electrodes together form one pole, and the external electrode forms the other pole). In this way, the stimulating system can create an electric field that substantially passes through the phrenic nerve between one or more intravascular electrodes and the patch. In this manner, the electric field stimulates the phrenic nerve, causing a contraction response of the diaphragmatic dome.

[0050] The stimulation system generates an electric field between one or more intravascular electrodes placed within the vena cava region and an external electrode placed on the patient's back, thereby facilitating stimulation by allowing the electric field to pass through the phrenic nerve. This configuration ensures that an electric field is formed between one or more points (one or more intravascular electrodes) close to the phrenic nerve and another point sufficiently far away on the anatomical opposite side of the phrenic nerve, while allowing for a tolerance in the placement of one or more intravascular electrodes within the vena cava region, and ensuring robust and stable access to the arteriovenous nerve. As a result, it is easier for the operator to position one or more intravascular electrodes at the start of the procedure. Furthermore, the stimulation is more stable; in other words, even if one or more intravascular electrodes are slightly displaced, it will not, at least substantially, affect the stimulation.

[0051] External electrodes, specifically electrode patches, generate a relatively large electric field, thus increasing the likelihood of passing through the phrenic nerve. This ensures reliable targeting of the phrenic nerve and provides more stable stimulation. Furthermore, this stimulation system is particularly easy to install. In fact, the external electrode patches are relatively easy to attach to the patient. Moreover, the use of patches allows for some tolerance in the placement of the external electrodes relative to the patient while still ensuring correct targeting of the phrenic nerve. Additionally, during the procedure, the patient may lie supine, and the position of the external electrodes may be at least partially between the patient and the operating table. Using patches reduces the risk of the external electrodes shifting if the patient's back moves relative to the operating table.

[0052] The stimulation system may include an energy source configured to conduct electricity to one or more intravascular electrodes via one pole (e.g., anode) and to an external electrode patch via the other pole (e.g., cathode or ground). The energy source, thus configured, generates an electrical signal that forms an electrical circuit between the one or more intravascular electrodes and the external electrode patch, separated by the electrical resistance of the patient's body. The energy source may include an electrophysiological signal generator adapted for phrenic nerve stimulation.

[0053] In the embodiment, the energy source may form an electrical circuit by delivering electrical pulses adapted to phrenic nerve stimulation. The voltage of each pulse is greater than 1V and / or less than 50V, and may be between 2V and 20V, for example, about 12V. Additionally or alternatively, the duration of each pulse may be greater than 0.1ms and / or less than 20ms, for example, between 0.5ms and 10ms, for example, about 2.9ms. The interval between two pairs of consecutive pulses may be constant or variable. In either case, the interval may be less than 20 seconds, 10 seconds or 5 seconds and / or greater than 50ms or 100ms, for example, between 100ms and 10 seconds, for example, about 1 second. Such an interval allows for reliable prediction well in advance of the onset of diaphragmatic paralysis. In fact, during cardiac cryoablation procedures, it takes about 30 seconds from the decrease in the diaphragmatic contraction response to the onset of diaphragmatic paralysis. The energy source may be configured to repeat the delivery of such pulses for at least 120 seconds, for example, for at least 180 to 240 seconds, during the cardiac cryoablation procedure. The energy source may be configured to repeat such repetitions at least twice consecutively (for example, within less than 10 minutes) in response to two cardiac cryoablation procedures on different right pulmonary veins of the same patient.

[0054] "Intravascular electrode" means a single conductive part of a stimulating catheter that is open to the outside and connectable to one electrode. At least one (e.g., each) intravascular electrode of the stimulating catheter may be made of a conductive material, such as a metal, such as gold, platinum, silver, and / or any suitable alloy. The stimulating catheter may be provided with one or more electrical leads, which are configured to supply electricity to each intravascular electrode. At least one (e.g., each) electrical lead may be, for example, a wire placed inside the stimulating catheter in one or more lumens, or a conductive path of an electrical substrate formed on the surface of the stimulating catheter, such as the inner surface of the stimulating catheter. The stimulating catheter may be provided with an electrical connector for connecting the catheter to an energy source, or to an electrical cord or cable connectable to the energy source (e.g., detachably), to supply power to each intravascular electrode via one or more electrical leads.

[0055] At least one (e.g., each) intravascular electrode of the stimulating catheter may be in the form of a pad (i.e., an isolated block of conductive material separated by a curve) formed on the outer surface of the stimulating catheter and facing at least a portion of the vein wall. The pad may be of any shape, e.g., square, circular, or any elongated shape where the length is greater than the width, e.g., roughly rectangular or roughly elliptical. The “length” and “width” of the pad refer to the maximum and minimum Euclidean distance between a pair of points on the pad when projected onto a plane substantially parallel to the pad. In addition, or as an alternative, instead of a pad, at least one (e.g., each) intravascular electrode may be in the form of a ring formed around the outer surface of the stimulating catheter.

[0056] The length of at least one (e.g., each) intravascular electrode of the stimulating catheter may be greater than 0.5 mm and / or less than 2.5 cm, for example, between 5 mm and 10 mm. Additionally, or alternatively, the width of at least one (e.g., each) intravascular electrode of the stimulating catheter may be greater than 0.3 mm and / or less than 2.5 mm, for example, between 2 mm and 2.3 mm. A larger area provides a contact area that can carry a larger current, enabling robust and stable stimulation of the phrenic nerve. A suitable compromise between flexibility and electrical conductivity lies in a length between 5 mm and 10 mm and a width between 2 mm and 2.3 mm.

[0057] The stimulating catheter may include one or more radiopaque markers to enable the precise placement of one or more intravascular electrodes, for example, using fluoroscopic imaging. Additionally, or alternatively, such placement may be performed using electromapping.

[0058] The stimulating catheter may have one intravascular electrode or multiple intravascular electrodes. In the case of multiple intravascular electrodes, the stimulation is further improved. The stimulation method may include, in particular, the step of operating the patch and several intravascular electrodes in bipolar mode. This further expands the electric field, increasing the probability of stimulating the phrenic nerve and thus improving stability. Additionally, or alternatively, the stimulation method may include the step of selecting one or more intravascular electrodes from several to operate the patch in bipolar mode. One or more intravascular electrodes selected from the multiple may satisfy any predetermined conditions relating to the quality of stimulation, for example, predetermined conditions relating to the position (for each selected intravascular electrode). For example, the stimulating catheter may additionally include radiopaque material markers placed near the intravascular electrodes. For example, only intravascular electrodes in contact with the inner wall of the vessel in the vena cava region may be selected. These electrodes are optimal for performing stimulation efficiently and stably, as will be further described later regarding the optional expandability of the stimulating catheter. The stimulation method may include the step of determining such electrodes by any technique, for example, electromapping. Therefore, the presence of multiple intravascular electrodes provides the operator with greater flexibility and facilitates the placement of the stimulating catheter. Additionally, and / or alternatively, the stimulation method may include a step of determining such electrodes by fluoroscopic imaging, thereby particularly facilitating the operator's manipulation of the stimulating catheter placement.

[0059] Next, we will further explain the case of a stimulating catheter that includes multiple intravascular electrodes.

[0060] Multiple intravascular electrodes may consist of five or more electrodes. This allows for strong stimulation of the phrenic nerve. Additionally, or alternatively, multiple intravascular electrodes may consist of fewer than 20 electrodes. This allows for wider spacing between electrodes. For example, an intravascular electrode system may consist of 8, 9, 10, 11, or 12 electrodes. This represents a suitable compromise.

[0061] Multiple intravascular electrodes may be spaced apart along the stimulating catheter. This ensures mechanical flexibility at the distal end of the stimulating catheter. The electrodes may be spaced at a predetermined fixed distance or at different distances. In either case, the distance between consecutive pairs of electrodes may be greater than 4 mm. This provides relatively high mechanical flexibility. Additionally, or alternatively, this distance may be less than 18 mm. This provides strong stimulation of the phrenic nerve. This distance may be approximately 9 mm, representing a good compromise between mechanical flexibility and stimulation intensity.

[0062] The size, number, and spacing of the intravascular electrodes described above are designed to ensure that the electrodes are well-suited for electrical stimulation, particularly phrenic nerve stimulation.

[0063] Multiple electrodes may consist of multiple electrodes electrically connected to each other, and thus only be able to form a single electrode. Optionally, the multiple electrically connected electrodes may be supplied via a single common electrical lead wire (e.g., a wire or conductive path). Alternatively, a single “discontinuous” electrode could be described, but this disclosure describes multiple electrically connected electrodes. Multiple electrically connected electrodes may be obtained, for example, by covering a portion of a stimulating catheter with a metal layer and discontinuously covering the metal layer with an insulating pad. Alternatively, multiple electrically connected electrodes may be obtained, for example, by covering a portion of a stimulating catheter with a metal layer, covering the metal layer with an insulating layer, and then forming a series of discontinuous openings on the insulating layer. The insulating layer may be positioned to cover an outer surface that does not face or touch the inner wall of a vena cava region. For example, in one or more intravascular electrodes positioned on the expandable portion of a catheter as described later, the insulating layer may cover the inner surface of the expandable portion that comes into contact with blood rather than body tissue. Additionally, or as an alternative, the insulating layer may insulate one or all of the catheter.

[0064] Additionally or alternatively, the multiple electrodes may consist of multiple individual electrodes that are electrically isolated from each other and capable of operating independently of each other. Optionally, each such individual electrode may be supplied via its own dedicated electrical lead wire (e.g., a wire or conductive path), and the stimulation system may have multiple electrical lead wires (e.g., wires and / or conductive paths), each dedicated to its respective electrode. The stimulation system may be configured to selectively operate individual electrodes in bipolar mode using an external electrode patch, and the stimulation method may include such selective operation. Additionally or alternatively, the stimulation system may be configured to selectively operate a group of individual electrodes to form a monopole capable of operating in bipolar mode with the external electrode patch, and the stimulation method may include such selective operation. “Selective operation” means that the stimulation method includes the step of selecting one or more electrodes, connecting the selected electrodes to an energy source, and then supplying energy. Optionally, the stimulation method may alternate between different selective operations in which different individual electrodes or groups of individual electrodes are selected and operated. Additionally, or alternatively, the stimulation system may be configured to operate multiple individual electrodes together to form a monopolar electrode with an external electrode patch that can operate in bipolar mode, and the stimulation method may include such operation.

[0065] In some embodiments, one or more intravascular electrodes may consist of multiple electrodes, and the system is configured to operate the multiple electrodes to simultaneously deliver electrical pulses between the individual electrodes of the multiple electrodes and the extracorporeal electrode patch. In such embodiments, the multiple electrodes may consist of 5 to 20 electrodes, for example, 10 electrodes.

[0066] "Operating one or more intravascular electrodes and an extracorporeal electrode patch in bipolar mode" means that the extracorporeal electrode patch may form one pole and the (selected) intravascular electrodes may form another pole, thereby creating an electric field between the two poles. For example, the extracorporeal electrode patch may form the cathode, while one or more intravascular electrodes may form the anode. Alternatively, the extracorporeal electrode patch may form the anode, while one or more intravascular electrodes may form the cathode. Optionally, the stimulation system may be configured so that the polarity of the extracorporeal electrode patch and one or more intravascular electrodes alternates.

[0067] The external electrode patch may be any medical patch or pad having a conductive surface configured to form a single unipolar electrode, be positioned in contact with the patient's back or right side, and remain substantially fixed during the stimulation method to connect to a certain potential. The conductive surface causes surface contact between the patch and the patient, rather than point contact such as that of an electrode pencil or electrode stylet. Thus, the patch amplifies the electric field generated between a single-point return electrode or midpoint electrode and one or more intravascular electrodes. The patch may be configured for single use or multiple use.

[0068] The conductive surface may include a conductive substrate configured to be in direct contact with the patient's skin. The conductive surface may have any shape. For example, the conductive surface may consist of a single conductive region, where each pair of points in the single region is connected by at least one continuous conductive path. Alternatively, the conductive surface may include a plurality (e.g., two, three, or four) such conductive regions separated from each other by non-conductive regions. In such a case, the plurality of conductive regions may be collectively connectable to a single potential to form a single monopole capable of operating in bipolar mode with one or more (e.g., selected) intravascular electrodes. Optionally, the plurality of conductive regions may be selectively connectable to a single potential to form a single monopole capable of operating in bipolar mode with one or more (e.g., selected) intravascular electrodes. In the embodiment, the stimulation system may be configured to selectively operate in bipolar mode any combination of intravascular electrodes and any combination of isolated conductive regions of the patch.

[0069] Optionally, a single region or at least one of several regions (e.g., each) may be substantially flat. Alternatively (additionally or alternatively, each), a single region (at least one of several regions, e.g., each) may form, for example, a regular or irregular grid pattern. In all cases, the conductive substrate may optionally occupy 10%, 20%, 50%, 75%, or 90% or more of the convex envelope of the entire conductive surface.

[0070] The conductive surface may be any elongated shape, such as a roughly rectangular or elliptical shape, where the length is greater than the width. The "length" and "width" of the conductive surface refer to the maximum and minimum Euclidean distance between a pair of points on the conductive surface when the patch is attached to a plane. The elongated shape allows the external electrode patch to be attached in a stimulation method such that it extends along the patient's back or right side (i.e., longitudinally along the patient's back) or transversely. This improves the stability and robustness of the phrenic nerve stimulation.

[0071] The conductive surface may be large enough to improve the stability and robustness of phrenic nerve stimulation. In particular, the length of the conductive surface may be greater than 1 cm, 2 cm, 4 cm, 8 cm, or 12 cm. Additionally, or alternatively, the width of the conductive surface may be greater than 1 cm, 2 cm, 3 cm, 4 cm, or 5 cm. For example, the conductive surface may be greater than 1 cm in length and greater than 1 cm in width, or greater than 2 cm in length and greater than 1 cm in width, or greater than 4 cm in length and greater than 2 cm in width, or greater than 8 cm in length and greater than 4 cm in width, or greater than 12 cm in length and greater than 4 cm in width, or greater than 12 cm in length and greater than 5 cm in width.

[0072] The conductive surface may be small enough to facilitate attachment to the patient's back. In particular, the length of the conductive surface may be less than 40 cm or 30 cm, and / or the width of the conductive surface may be less than 30 cm or 20 cm. For example, the conductive surface may be less than 40 cm in length and less than 30 cm in width, or less than 30 cm in length and less than 30 cm in width, or less than 30 cm in length and less than 20 cm in width.

[0073] For example, the conductive surface may have a length between 15 cm and 25 cm, such as approximately 20 cm in length and approximately 10 cm in width, and a width between 5 cm and 15 cm in width. Optionally, the conductive substrate may occupy 75% or more, for example 90% or more, of the convex envelope of the entire conductive surface.

[0074] The patch may have a conductive layer in contact with the patient's skin. The conductive layer may be made of any conductive material, such as a metallic material, a conductive gel, or even conductive rubber. The conductive gel layer may be supported by a silicone layer. The patch may optionally have an outer insulating layer on the opposite side of the conductive surface, such as the silicone layer itself (insulating), or an additional layer made of, for example, plastic or fabric material. The patch may have an electrical connector (e.g., a plug or one or more tabs) for connecting an electrical cord or cable to the conductive layer (e.g., detachably). The electrical cord or cable may allow connection to an energy source, in particular its potential. Alternatively, the patch may have such an electrical cord or cable permanently attached.

[0075] The conductive layer may be made of a flexible material, and the patch itself may be flexible. If the conductive layer is made of a metallic material, the metallic material may be a flexible metallic sheet. Its flexibility allows it to conform to the shape of the patient's body, and the surface makes better contact with the patient's body, thereby improving the stability and robustness of phrenic nerve stimulation. Alternatively, the patch may consist of a rigid plate, such as a rigid metal plate, optionally comprising a surface layer made of a conductive gel, and the patient may lie with their back on the plate (or on the gel layer, if any). The patient's weight may provide relatively good contact between the patient's back and the plate.

[0076] The patch may further include an adhesive coating, which makes the external electrode patch self-adhesive. This ensures the patch remains securely attached to the patient's back during the procedure. In fact, the adhesive coating prevents the patch from shifting during medical procedures, especially during phrenic nerve stimulation. It also allows the operator to quickly attach the patch to the patient without the use of additional fixing materials or adhesives. The adhesive coating may be conductive and may partially or completely cover the conductive layer. This makes it easier to maintain the patch in place. Alternatively, the adhesive coating may surround the conductive layer.

[0077] Therefore, as mentioned above, the conductive surface may be either the surface of an uncoated conductive layer in contact with the patient's skin, or, if present, a conductive adhesive coated surface. Furthermore, as mentioned above, the expression "attached to the patient" simply means that the patch remains in a substantially fixed position relative to the patient's body during the procedure. This may optionally be achieved by attaching the patch to the patient's back by adhesive as described above, or by other means (such as taping, or wrapping the patient's upper body with clothing), but is not required.

[0078] An example of an adhesive metal patch covered with a plastic outer layer, used in the experiment described later, is the Erbe NESSY® Plate 170 Split. This patch has a conductive surface divided into two separate conductive areas. The patch has a total area of ​​168 cm². 2 It is roughly rectangular, approximately 20 cm long and 8 cm wide.

[0079] The stimulating catheter is configured to be introduced and operated in the superior vena cava. The stimulation method may be minimally invasive, and therefore the stimulating catheter may be configured to be introduced, for example, through the femoral vein. Accordingly, the stimulating catheter is sufficiently flexible, sufficiently long, and sufficiently small in diameter. For example, the outer diameter of the stimulating catheter may be 4 Fr or more and / or 10 Fr or less, for example 6 Fr, 7 Fr, or 8 Fr. The length of the catheter may be greater than 90 cm and / or less than 200 cm, for example equal to about 145 cm.

[0080] The stimulating catheter may be equipped with positioning means.

[0081] For example, the stimulating catheter may include a guidewire (e.g., made of metal) configured to guide the catheter into a superior vena cava. The guidewire may be located within the lumen of the catheter body and protrude from the distal end of the catheter body. The diameter of the guidewire may be greater than 0.020” and / or less than 0.060” and preferably greater than 0.030” and / or less than 0.040” and equal to, for example, 0.032” or 0.035”. The guidewire may be inserted into a hemostatic valve. The stimulating catheter may further include a lavage lumen. In one embodiment, the guidewire is made of a hydrophobic material.

[0082] Alternatively, the stimulating catheter may have a body with a lumen configured for the insertion of a positioning mandrel. The lumen may be closed at the distal end of the catheter body so that the mandrel does not protrude from the catheter body. The stimulating catheter may further include such a mandrel.

[0083] Figure 2 shows an example of a stimulation method using a schematic example of a stimulation system. As shown, the operator may perform the stimulation method by attaching an external electrode patch 260 to the patient's back. In particular, as can be seen from the figure, the patch 260 may be substantially rectangular in shape and / or its length may be greater than its width, and the stimulation method may include the step of attaching the patch 260 so that it extends along the patient's back. Specifically, the patch 260 may be attached to the right paravertebral region, facing the medial portion of the right scapula and reaching the tip of the right scapula. In a variation, the patch 260 may be attached to the patient's back so as to extend laterally and / or to another location opposite the distal portion 240 to the phrenic nerve. As schematically shown, this method may include the step of introducing the distal portion 240 of the stimulation catheter 200 into the patient's superior vena cava VC. The stimulating catheter 200 is positioned so that its distal end 240 faces the phrenic nerve (not shown) across the patch 260. At this position, the phrenic nerve is located between the distal end 240 of the stimulating catheter 200, which carries one or more intravascular electrodes (not shown), and the patch 260. Thus, an electric field may be generated between them by using an energy source (not shown) having one pole electrically conductive with the intravascular electrode on the distal end 240 and the other pole electrically conductive with the patch 260 via an electrical cord 262. The electric field closes the circuit passing through the phrenic nerve. Thus, the phrenic nerve can be stimulated. The wide conductive surface area of ​​the patch 260 allows for easy, robust, and stable capture of the phrenic nerve. This results in high ease of use for the operator, requiring only alignment of the stimulating catheter 200 in the vein to initiate the electric field. This may enable a more reliable cryoablation method by increasing the reliability of monitoring the diaphragmatic contraction response.

[0084] Figure 3 shows an example of a cryoablation system used in a cardiac cryoablation procedure performed on a human patient, which includes a stimulation system and a step of repeatedly performing the stimulation system throughout the cryoablation procedure.

[0085] The stimulation system comprises a stimulating catheter 300 including one or more intravascular electrodes 310 positioned on the distal portion 340 of the catheter, an extracorporeal electrode patch 360, and optionally an energy unit 313 including an energy source 311. The energy source 311 is connectable to the stimulating catheter 300 via an electrical cord 312 and electrical connector 314 of the stimulating catheter 300 to supply energy to the electrodes 310 via electrical leads 316 for each individual intravascular electrode 310 (or alternatively, via a common single electrical lead if there are multiple intravascular electrodes 310). The energy source 311 is further connectable to the patch 360 via an electrical cord 362. Thus, the energy source 311 is configured to operate the patch 360 and the intravascular electrodes 310 in bipolar mode.

[0086] The energy unit 313 may optionally include a processor, such as a CPU, connected to a memory such as a non-volatile memory, e.g., a hard disk and / or RAM, and the processor may be configured to control the energy source 311 to send electrical pulses configured for phrenic nerve stimulation, as described above. For this purpose, the memory may store a computer program containing instruction codes for operating the energy source 311.

[0087] A computer program may include instructions executable by a processor, which include means for causing the system to deliver electrical pulses of a stimulation method. The program may be writable to any data storage medium. The program may be implemented, for example, in digital electronic circuits, or in computer hardware, firmware, software, or a combination thereof. The program may be implemented, for example, as a device such as a product embodied in a machine-readable memory device for execution by a programmable processor. An application program may be implemented in a high-level procedural or object-oriented programming language, and, if necessary, in assembly language or machine code. In any case, the language may be a compiled language or an interpreted language. The program may be a complete installation program or an update program.

[0088] The cryoablation method may include the steps of applying a patch 360 to a human patient, having the patient lie supine on an operating table 390, and introducing an stimulating catheter 300 into the patient's superior vena cava, for example, by a minimally invasive procedure.

[0089] The cryoablation method may further include the step of providing a cryoablation catheter 380, such as a cryo-balloon catheter. The cryoablation catheter may be a cryo-balloon catheter 380 having a balloon 382 for cryoablation. The cryoablation method further includes the step of introducing the cryo-balloon catheter 380 into the left atrium of the patient's heart, for example, via a minimally invasive procedure (e.g., via the patient's femoral vein). The cryoablation method then includes the steps of performing cryoablation (i.e., cauterizing body tissue at a low temperature) and operating the patch 360 and intravascular electrode 310 in bipolar mode with an energy source 311 to repeatedly stimulate the patient's phrenic nerve by delivering pulses with an amplitude of about 10V and a duration of about several ms at a frequency of about 60 pulses per minute (1 pulse / second), for example.

[0090] The stimulation system may further include a unit for monitoring the diaphragm's response to phrenic nerve stimulation, for example, by objective analysis. This unit may include a sensing module 390, such as a CMAP (compound muscle action potential) sensing device or a gravimeter, which is placed on the patient's chest / abdomen. The unit may further include communication means 392, such as a cable or wireless module, for sending the measured values ​​to a monitoring module 394. The monitoring module 394 may include any means for outputting a display of the received measured values ​​to the operator, such as a display device, an alarm generator (for example, the alarm may be a visual and / or audible signal), and / or a printer (for example, one suitable for graphically representing the received measured values, such as printing on millimeter ECG paper). Such a monitoring unit may objectively, and therefore particularly accurately, observe the contraction of the diaphragmatic dome in response to phrenic nerve stimulation. Alternatively, the contraction of the diaphragmatic dome may be determined by palpation of the abdomen.

[0091] A decrease in response indicates that damage to the phrenic nerve is occurring. The cryoablation procedure may include a step to take this into consideration. For example, cryoablation may be paused, for example, when a decrease in response is observed or immediately after it is observed (for example, less than 20 seconds, 10 seconds, or 5 seconds after such observation). Cryoablation may only be resumed after the response has returned to a baseline state, i.e., recovery of the phrenic nerve is observed.

[0092] Because the stimulation system improves the stability of phrenic nerve stimulation, the reliability of the monitored diaphragmatic response is enhanced, making cryoablation safer and / or faster to perform in relation to phrenic nerve damage.

[0093] The systems disclosed herein may be provided as kits for phrenic nerve stimulation. The kits include a stimulation system or a system for cardiac cryoablation. The kits further include instructions (e.g., recorded on a physical carrier) for phrenic nerve stimulation of a human patient during cardiac cryoablation. For example, the kits may include paper carriers such as handbooks or leaflets containing explanations in the form of text and / or pictograms. Alternatively, the kits may include computer-readable media such as USB drives containing such text and / or pictograms in computer files. Further alternatively, the instructions may be downloadable, for example, via a URL indicated on the physical carrier of the kit. The instructions may describe the procedure for phrenic nerve stimulation and, optionally, refer to cryoablation. Optionally, the kits may further include instructions for monitoring the diaphragmatic response to phrenic nerve stimulation and / or instructions for performing cardiac cryoablation. In other words, the instructions may include descriptions of any embodiments of the stimulation or cryoablation methods disclosed herein.

[0094] In the embodiment, the distal portion of the stimulating catheter may be provided with an expandable portion, and therefore the stimulating catheter may have both an expanded and an unexpanded configuration. “Expandable portion” means that the portion is deformable so that its diameter (i.e., the maximum width of that portion perpendicular to the longitudinal axis of the catheter, i.e., the longitudinal axis of the vena cava) can be increased compared to the diameter of the catheter (i.e., the diameter of the non-expandable portion of the catheter), possibly until it is in close contact with the inner wall of the vein. The maximum diameter of the expandable portion (i.e., when fully expanded) may be at least 5 times, and even more than 10 times, the diameter of the catheter. The expandable portion may include the distal end of the distal portion of the stimulating catheter and is therefore displaceable relative to the longitudinal axis of the catheter. Alternatively, the expandable portion may be formed and terminated at a proximal position different from the distal end of the stimulating catheter, and therefore remain on the longitudinal axis of the catheter when the expandable portion is expanded. The stimulating catheter may be reversibly deformable between an expanded and an unexpanded configuration. Therefore, the operator may insert the expandable portion to expand the stimulating catheter within the vena cava region, manipulate the catheter, and then return the expandable portion to its straight, unexpanded state in order to withdraw the catheter.

[0095] The stimulating catheter may be adjustable and expandable. Therefore, the operator may adjust the expandable portion to maintain the distal end in a fixed position on the vena cava, particularly in a position relatively close to the phrenic nerve. Alternatively, the expandable portion may be automatically expandable. In such a case, expansion only needs to be initiated, and the catheter may self-deploy to its expanded state.

[0096] The expandable portion may be configured to conform, for example, circumferentially to the inner wall of the superior vena cava or the inner wall of the right subclavian vein.

[0097] To “match” the inner wall of a vein (i.e., either the internal tissue branching from the vena cava into the right subclavian vein or the brachiocephalic vein) means that the expandable portion is configured to expand to at least the diameter of the vein and maintain a stable position in contact with the inner wall of the vein. For example, the diameter of the expandable portion may be greater than 10 mm, 20 mm, 25 mm, 30 mm, 35 mm, or 40 mm, for example, about 50 mm. This allows it to match the vessels of the vena cava region. The larger the diameter of the expandable portion, the more reliably it will match, especially to the vena cava. The expansion may be adjustable. Thus, the operator may insert the expandable portion into the vessels of the vena cava region and adjust the expandable portion to fit its size. Alternatively, the expansion may not be adjustable; for example, when expansion is initiated, the diameter may increase until it is limited by the inner wall of the vessels of the vena cava region. The expandable portion may be made of a relatively soft material (like other parts of the catheter, for example), so that it can interlock with the vessels of the vena cava region without causing damage. The expandable portion makes it easier to maintain the stimulation catheter in place during manipulation and provides stability, thereby improving the ease of operation and stability of phrenic nerve stimulation. In its expanded form, the expandable portion may have a diameter between 10 mm and 35 mm, for example.

[0098] "Circumferentially conforming" means that the expandable portion conforms to a circular cross-sectional area in three-dimensional space. In other words, the expandable portion itself does not necessarily have to have a solid circle, or a cylindrical or spherical three-dimensional space; it is sufficient that it conforms to a circular cross-sectional area. Therefore, the expandable portion is suitable for conforming to the wall of a vein whose inner wall has a circular cross-sectional area. This improves the stability of the catheter's position. In fact, the operator may expand the expandable portion within the vein wall (for example, by manual adjustment or activation of automatic deployment). The cryoablation method may then include a step of performing cryoablation while the catheter automatically remains in a stable position. Therefore, the operator may manipulate the intravascular electrodes of the patch and catheter to repeatedly and robustly stimulate the patient's phrenic nerve during cryoablation, due to the effect of stable positioning.

[0099] The circumferential fit may be such that the catheter remains in place. In other words, the maximum diameter of the expandable portion may be greater than the diameters of the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein, so that there is a certain level of friction when the expandable portion is expanded, and the catheter remains substantially in place during its movement (unless a force greater than the friction is applied). Thus, the expandable portion functions as a fixation point. In fact, this fit allows the blood vessel to hold the expandable portion and function as a fixation point.

[0100] In the embodiment, at least one (e.g., some or all) intravascular electrodes may be positioned on the expandable portion. This brings such electrodes closer to the inner wall of the vena cava region, thereby improving electrical connectivity and, consequently, the stability of phrenic nerve stimulation. In particular, at least one (e.g., some or all) intravascular electrodes may be positioned on the expandable portion so as to contact the inner wall of the vena cava region when the catheter is in an expanded state. "Contact" means that there is no gap between the intravascular electrode and the inner wall through which blood can pass. In other words, the intravascular electrodes in the expandable portion have a position, orientation and dimensions such that at least one intravascular electrode is in contact with the inner wall of the vena cava region. Thus, conductivity between the catheter and the extracorporeal patch is improved, as opposed to allowing blood to pass between the electrode and the vein wall. Thus, the stability of phrenic nerve stimulation is further improved. In particular, to optimize the stability of the electric field and improve operation in bipolar mode with the external electrode patch, all intravascular electrodes may be positioned to contact the inner wall of the superior vena cava or the right subclavian vein.

[0101] In the embodiment, one or more intravascular electrodes may be arranged on the circumference of the expandable portion. "Arranged on the circumference" means that each of the one or more intravascular electrodes is positioned along the diameter of the cross-sectional area of ​​the expandable portion. In other words, each of the one or more intravascular electrodes is spaced at a fixed distance from each other in the circumferential direction along the cross-sectional view of the wall of the expandable portion.

[0102] The arrangement along the diameter may cover the entire diameter or only a portion of the diameter. The extent of the arrangement may be measured by the angle between the positions of the first and second ends of the expandable portion, which define the beginning and end of the arrangement along the diameter. The first and second ends may be selected according to convention. An angle of 360 degrees (i.e., the same position) between the first and second ends from the center of the circumference means that the arrangement covers the entire circumference. One or more intravascular electrodes may be placed between the first and second ends.

[0103] In the embodiment, one or more intravascular electrodes, for example, ten intravascular electrodes, may be arranged at equidistant angles with respect to each other and to the first and second ends. In other embodiments, the intravascular electrodes may be arranged at different angles. For example, in the intermediate portion between the first and second endpoints, the intravascular electrodes may be closer to each other. The circumferential arrangement of one or more intravascular electrodes may be at different longitudinal positions along the three-dimensional space or region covered by the expandable portion, and, optionally, other intravascular electrodes may be placed in the non-expandable portion of the stimulating catheter.

[0104] For example, several longitudinal rows, each aligned with the axial direction of the catheter, are arranged circumferentially. In another embodiment, three rows may be separated by a 120° angle, or four rows may be separated by a 90° angle. In yet another embodiment, the rows may be separated by different angles, for example, three rows may be separated by a 60° angle and two rows by a 90° angle.

[0105] The circumferential arrangement ensures that at least one electrode, or a row of electrodes, substantially or nearly faces the wall of the superior vena cava anterior to the phrenic nerve, thereby ensuring that the electrodes are in close proximity to the phrenic nerve. Generally, the stimulation method may include the step of positioning at least one (e.g., several or all) intravascular electrodes against the portion of the inner wall of the vena cava facing the phrenic nerve. In other words, there exists a straight path from the nerve to the portion of the vena cava that does not encounter, for example, another portion of the vena cava, or another type of tissue, which would prevent the inner wall of the vena cava from entering the straight path of the nerve. This arrangement ensures that the operator ensures that the electric field therein, or at least a portion of the electric field, directly stimulates the phrenic nerve and provides the stimulation necessary to assess diaphragmatic monitoring. If the distal portion comprises an expandable section carrying one or more intravascular electrodes arranged circumferentially, such an arrangement is very easy to operate, as the operator only needs to activate or adjust the expansion of that section to correctly position at least one or a row of electrodes. As a result, stimulation is more reliable. As described above, to improve efficiency, one or more such properly positioned electrodes may be selected by mapping and operated exclusively. Alternatively, radiopaque materials may be used to properly position the catheter.

[0106] In addition to or as an alternative to being expandable, the stimulating catheter may be bendable at its distal end. Flexibility means that the distal end may be bent in at least one direction relative to the body of the catheter. The maximum bend may be greater than 10 degrees and / or less than 90 degrees. In embodiments, the maximum bend may be greater than 25 degrees so that the expandable portion can be positioned in the right subclavian vein. The stimulating catheter may be equipped with a pull wire for providing the bend.

[0107] In one embodiment, the catheter may have a non-expandable distal end after the expandable portion. In other words, the non-expandable distal end does not expand and therefore remains in its original shape even when the catheter is expanded. In certain embodiments, the non-expandable distal end may be linear and remain linear within the catheter axis (i.e., the axis of the blood vessels in the vena cava region) even when the catheter is in an expanded state. The length of the non-expandable distal end may be, for example, greater than 1 cm and / or less than 12 cm, and may be, for example, between 1.5 cm and 4 cm.

[0108] Next, embodiments of the expandable portion will be described. The expanded form may be spiral (i.e., vortex), loop, lasso, umbrella, or basket-shaped. Such embodiments have in common that the expandable portion may be equipped with a blood flow passage when expanded in order to reduce the risk of obstructing blood flow during catheter expansion.

[0109] "Spiral / vortex configuration" means that the material of the expandable portion has a shape formed by one or more spiral coil segments connected in series between a proximal endpoint of the distal portion and another endpoint longitudinally away from the distal endpoint. Each of the one or more spiral coil segments consists of the material of the expandable portion wound one or more times around a cylinder. For example, the material of the expandable portion may be a wire-like material or a flexible material suitable for such a configuration. Thus, the spiral configuration forms an open solid space defined by the cylindrical solid space inside the internal solid space of the spiral coil segment and the endpoint, and the spiral coil segment may be in contact with the inner wall of the vena cava region vessel without obstruction of blood flow. The diameter of one turn of the spiral configuration may be constant or variable. The spiral configuration is sometimes called a "vortex configuration," but in this disclosure, the latter term is given a different meaning, as will be explained below.

[0110] In one embodiment, the spiral or vortex formed by the expandable portion may, in its expanded form, be a coil of up to two turns, in other words, a coil of any number of turns up to two turns, for example, (strictly) one turn, one and a half turns, or two turns (wherein "coil" or "vortex" is strictly one turn of the spiral or vortex). A coil of up to two turns is easy to manufacture and use, and less cumbersome, as increasing the number of coils further would make the structure excessively complex and risk losing its original shape. In certain embodiments, the catheter may have a non-expandable distal end (e.g., a straight one), and the expandable portion may consist of a coil of up to two turns in its expanded form. In such embodiments, the operation of the system is simplified in that the two-turn coil can recover its shape after insertion, and the non-expandable distal end allows the two-turn coil to maintain its desired shape. The non-expandable distal end may improve not only the placement of the two-turn coil but also its repositioning within the vessels of the vena cava region. The non-expandable distal end counteracts the effect of a small number of coil turns on stability.

[0111] In further embodiments, in a helical or spiral configuration, the pitch or height of a complete turn of the spiral or spiral may be between 5 mm and 15 mm. Increasing the pitch may help maintain the original shape of the helical or spiral configuration when the positioning means are removed. In another embodiment, if the pitch is increased in a helical or spiral configuration, this may be assisted by a non-expandable distal end. In other words, the non-expandable distal end may help the configuration maintain such an increased pitch.

[0112] A “loop configuration” means that the material of the expandable portion is a closed shape that traces a circular or substantially circular (e.g., elliptical) shape. Thus, this shape traces a closed circular or elliptical path that remains in contact with the inner wall of the blood vessel in the vena cava region while maintaining space between them, so that blood can flow through the expandable portion. The loop may be contained in any plane, for example, the longitudinal plane of the catheter, or the cross-sectional plane (for example, perpendicular to the longitudinal axis of the catheter).

[0113] The term "lasso-like configuration" means that the material of the expandable portion has a closed shape that traces a spiral shape of up to one turn from the base of the proximal endpoint of the distal portion. Thus, this shape traces a circular path that remains in contact with the inner wall of the blood vessel in the vena cava region while maintaining space between them, so that blood can flow through the expandable portion. The lasso portion may be contained in any plane, for example, the longitudinal plane of the catheter, or alternatively (for example, perpendicular to the longitudinal axis of the catheter) in a cross-sectional plane.

[0114] The term "umbrella-shaped structure" means that the expandable portion is composed of multiple segments extending radially outward from the proximal endpoint of the distal portion. The outermost endpoints of the segments may be connected by a mechanism that stabilizes the segments in their expanded position. For example, this mechanism may extend one or more outermost endpoints along the circumference. Since the spaces between the segments are not blocked, blood can flow through the expandable portion.

[0115] The "cage-like configuration" means that the expandable portion consists of one or more segments, each interconnected, between the proximal endpoint of the distal portion and an endpoint located longitudinally from the distal endpoint. Each segment is positioned at different angles to the distal endpoint. Each segment maintains the same angle at the far end. In the expanded form, each segment traces the circumference between both endpoints. The width of the segments may be such that space is left between each segment, allowing blood to flow. Thus, this configuration allows contact with the inner wall of the blood vessels in the vena cava region without obstructing blood flow.

[0116] The stimulating catheter may further include one or more operator-operable mechanisms for deforming the expandable portion of the stimulating catheter from a linear configuration to one of the expanded configurations described above. For example, the stimulating catheter may include one or more pull wires operable for deforming the stimulating catheter to an expanded configuration, and optionally, a handle for operating the one or more pull wires. The operator may operate the pull wires to deform the expandable portion via an appropriate mechanism for expanding the expandable portion. Such a mechanism provides the operator with a high degree of ease of use in adjusting the stimulating catheter to fit the vascular wall in the vena cava region, although the mechanism may vary depending on several factors. The operator may adjust the expandable portion based on their medical assessment before performing phrenic nerve stimulation to enable placement of the stimulating catheter for stable electrical stimulation. Additionally or alternatively, the expandable portion may be made of shape-memory material, at least partially. Thus, the shape-memory material may bias the expandable portion to an expanded configuration. In such cases, the expansion may be initiated in any manner. Optionally, the catheter may include a retractable sheath covering the expandable portion and / or a retractable straightening inner member (e.g., a straightening wire or mandrel, which also functions as a positioning means, such as a guidewire or positioning mandrel) that straightens the expandable portion to enable insertion of the catheter into the superior vena cava. When such a member is retracted, the biasing force is released, and the portion automatically expands due to the shape memory of the material. Such a mechanism improves the stability of the position within the vein.

[0117] Instead of having an expandable portion, the catheter may be a straight catheter. In such cases, the catheter may optionally be bendable.

[0118] Next, embodiments of the stimulating catheter will be described with reference to Figures 4 to 10. Although the descriptions of the figures largely focus on the superior vena cava, as mentioned above, the same applies to other vena cava regions. In these embodiments, the stimulating catheter has an expandable portion, as previously described. The embodiments described below detail several extended forms of the stimulating catheter that provide the operator with ease of operation when placing at least one intravascular electrode and provide stable stimulation of the phrenic nerve.

[0119] Figure 4 shows an example of a stimulating catheter 400 having a helical configuration. The stimulating catheter 400 comprises a distal section 440, an electrical connector 414, and a lumen inlet 472. The lumen inlet 472 may be configured, for example, to introduce a guidewire 470. The guidewire 470 protrudes from the tip 444 of the distal section. The guidewire 470 may be configured to allow an operator to position the distal section 440 within a blood vessel in the vena cava region. The electrical connector 414 may be connected to an electrical lead wire. The distal section comprises an expandable section 442. The expandable section comprises a plurality of intravascular electrodes 410 arranged on its circumference. Alternatively, the expandable section may comprise a single elongated electrode extending along the circumference of the expandable section 440. The expandable section 442 may be adjusted or self-expanding so that the intravascular electrodes 410 are positioned on the outer portion of the wall of the expandable section 442 to conform to the wall of a vein. Optionally, the material of the tip 444 may be made of a flexible material that acts as a guide. Optionally, the catheter may include a retractable sheath (not shown) covering the expandable portion 442, and / or a retractable straightening inner wire (not shown) that straightens the expandable portion, enabling insertion of the catheter into the superior vena cava. Retracting such a sheath and / or straightening inner wire may expand the helix and / or initiate such expansion. The principle shown in this figure also applies to other forms of expanded embodiments. However, in such cases, the guidewire 470 may not always be contained within a lumen formed in the catheter body as in the figure, but may sometimes protrude from the catheter body, particularly from the expandable portion.

[0120] Figures 5A and 5B show a catheter 500 with an expandable lasso section 542. The expandable lasso section 542 may appear to be a single-turn helical shape winding upward toward the end 544. Multiple intravascular electrodes 510 are arranged, for example, at equal intervals, on the circumference of the expandable section 542. Each electrode 510 is positioned facing outward to maximize contact with venous tissue. The electrodes are positioned between the tip 544 of the expandable section 542 and the catheter body 500. The lasso section may be compressed or straightened in its unexpanded form to allow insertion into the stimulating catheter. In the expanded form, the operator may increase the diameter D of the lasso section along the cross-section to conform to the venous wall, for example, using a pull wire operated with one or more specially configured handles. This configuration can be easily deployed to the expanded form by the user and remains physically stable. Because the electrodes are arranged circumferentially, the user can position the catheter at any angle within the vena cava.

[0121] Figures 6A and 6B show another embodiment of the catheter 600 when the expandable helical portion 642 is in a helical configuration and a linear configuration with the helical extended, respectively.

[0122] The spiral consists of loops along the longitudinal direction of the expandable portion 642. For example, the spiral may consist of two to five loops. The loops do not have to be complete. For example, the spiral may consist of two and a half loops. In the linear configuration, the expandable portion may be covered by a retractable sheath 602. The spiral may be expanded by an operator via a pull wire (not shown) connected, for example, through an end 620 that pulls in the sheath. The expandable portion may be made of a shape-memory material. Thus, the operator may retract the sheath, and the material returns the shape of the expandable portion to a spiral configuration. The spiral configuration may be adjusted by the loops of the spiral to conform to the inner wall of the vein and circumferentially matched. The spiral may comprise a plurality of electrodes 610 that may be arranged along the entire length of the spiral or a portion of the loops, i.e., all the loops of the spiral.

[0123] As shown in Figure 6A, each electrode 610 may be longer than its width, and multiple electrodes 610 may be arranged on the circumference of the expandable portion so as to extend substantially along the superior vena cava when the stimulating catheter is in an expanded state. In other words, the length of each electrode is substantially aligned longitudinally along the vein. This achieves an effective electric field.

[0124] Figure 6B schematically shows a stimulating catheter in a linear configuration. In the linear configuration, the electrodes are shifted by a slight angle compared to the expanded configuration along the same longitudinal axis due to the stretching of the spiral. Since the phrenic nerve substantially follows the vena cava, when the stimulating catheter is in the expanded configuration, the electrodes 610 may be aligned in several rows to deliver an electric field across the phrenic nerve. These rows are distributed circumferentially along the vena cava. Alternatively, the electrodes may be distributed over the entire circumference of the vena cava without forming such rows. This arrangement provides a high degree of ease of use, as the user does not need to worry about directly positioning the expandable portion near the phrenic nerve. Furthermore, the spiral configuration allows the operator to fix the expandable portion along a longitudinal section of the vena cava wall. Thus, the stimulating catheter remains in a fixed position, improving the stability of stimulation to the phrenic nerve.

[0125] Figure 7 shows another embodiment of the catheter 700 with an expandable portion 742, the expanded form of which is a horizontal loop configuration. The horizontal loop unfolds along a plane perpendicular to the longitudinal axis of the vein wall. For example, the horizontal loop configuration 742 unfolds perpendicular to the wall of the superior vena cava (VC). This is presented for illustrative purposes only. For example, the horizontal loop configuration 742 unfolds perpendicular to the wall of the right subclavian vein. The expandable portion 742 comprises horizontal loop segments forming an inward loop (in any direction) from the end portion 720.

[0126] When the catheter 700 is in an unexpanded state, the loop of the horizontal loop segment may contract along the longitudinal direction of the expandable portion and be held inside the sheath, becoming compact / straight relative to the stimulating catheter and allowing insertion through the femoral vein. The horizontal portion may be expanded by an operator using a pull wire or guide connected via the end 720. The pull wire or guide may be reversible and expansion may be performed automatically or manually, thereby allowing the operator to expand the horizontal loop in the cross-sectional direction to achieve circumferential matching to the vein.

[0127] The operator gains a high degree of ease of use. The operator can adjust the circumferential fit of the stimulating catheter to the vein VC by adjusting the cross-sectional diameter of the horizontal loop segment. The horizontal loop segment may have a single electrode, which may be positioned along the longitudinal direction of the horizontal loop segment, i.e., along all or part of the horizontal loop, i.e., along only some of the loops of the horizontal loop segment. Optionally, multiple intravascular electrodes 710 may be positioned along the horizontal loop. Figure 7 shows multiple electrodes positioned only in the area in contact with the wall of the vein VC. The stimulating catheter is fixed and kept stable by the horizontal loop segment that is adjusted to the vein wall, thereby improving the stability of phrenic nerve stimulation.

[0128] Figure 8 shows another embodiment of the catheter 800 with an expandable portion 842, the expanded configuration of which is a vertical loop. The vertical loop configuration includes an intravascular electrode 810 positioned on the outward-facing surface of the vertical loop. Figure 8 shows the vertical loop 842 expanding along the longitudinal axis of the superior vena cava (VC). This configuration is shown for illustrative purposes only; alternatively, the vertical loop may expand along the longitudinal axis of the right subclavian vein. The electrode 810 is positioned along the longitudinal section of the loop that is in contact with the vein wall. The vertical loop may be in a compressed configuration by being pulled toward the end 820 to allow insertion of the stimulating catheter. In the expanded configuration, the operator may increase the diameter of the vertical loop (automatically or manually) to conform to the vein wall.

[0129] Figure 9 shows another embodiment of the catheter 900 with an expandable section 942, where the expanded configuration is umbrella-shaped. The expandable section 942 of the umbrella configuration may consist of another flexible "rib" (i.e., segment), the end of which is connected to the end 920 on the expandable section 942 of the stimulating catheter 900, and the other end of which is connected radially by a radial end connector 946. In the linear configuration, the segments may be grouped together along the longitudinal direction of the stimulating catheter, as the radial end connector 946 may be retracted by the operator. When the stimulating catheter is in the expandable configuration, the radial end connector 946 is in the expanded configuration, thereby being displaced outward toward the vein wall. In other words, the umbrella ribs unfold along the vein wall. Figure 9 is a longitudinal view showing the outwardly expanded ribs. This displacement may be reversible, and the fixed position of the ribs may be set between the linear configuration and the maximum displacement allowed by the radial end connector 946. One or more electrodes 910 may be placed on each rib.

[0130] Figure 10 shows another embodiment of the catheter 1000 with an expandable section 1042, where the expanded form is a cage-like configuration. The expandable section 1042 of the cage-like configuration may consist of several “splines.” Each spline is a segment with two ends. One end of each spline is connected to the proximal end 1020 of the expandable section 1042. The corresponding remaining ends of each spline are connected to each other by a mechanical connection to form a spline end 1044. Each spline may be made of a flexible material that allows for deployment from a linear configuration to an expandable configuration. In the linear configuration, the splines are stretched along the longitudinal section of the expandable section 1042, thereby forming a linear body that extends along the ends 1020 and 1044 and is parallel to the longitudinal axis of the catheter 1000. In the expandable configuration, the splines move outward, thereby creating a “cage” that encloses the three-dimensional space.

[0131] Figure 10 shows splines displaced circumferentially from ends 1020 and 1044. This is merely one embodiment. For example, each spline may trace a sectioned linear path connecting ends 1020 and 1044. Each spline comprises multiple intravascular electrodes 1010. The cage configuration may comprise more than two splines, such as four, eight, or more. Figure 10 shows intravascular electrodes 1010 arranged at equal intervals from one another in the center of the spline. The intravascular electrodes 1010 are positioned outward to contact the vein wall.

[0132] The disclosed stimulation methods and systems were evaluated using 3D simulations.

[0133] The 3D simulation involved representing a 3D model of the human body, including anatomical models of the heart and phrenic nerve, as well as the associated electrical resistance, within finite element analysis software. The 3D model included a catheter and a model of an attached extracorporeal patch. The 3D model was configured to represent the bipolar operation of an intravascular electrode with a patch electrode. The electric field was simulated to evaluate the efficient stimulation of the phrenic nerve. The simulation used a spiral catheter similar to the one shown in Figure 4, and a rectangular area of ​​20 cm in length and 8 cm in width, with a total area of ​​168 cm². 2 The simulation involved applying stimulation to the phrenic nerve using an extracorporeal patch. The simulation results were compared to the mean and optimal reference responses from a model of a quadrupole catheter, which is widely used for phrenic nerve stimulation.

[0134] The simulation results showed improvements of 80% and 26% compared to the average baseline response and the optimal baseline response, respectively.

[0135] The disclosed stimulation method and system were further experimentally tested on 49 kg pig subjects.

[0136] protocol:

[0137] A 49 kg pig, placed in a dorsal decubitus position and under general anesthesia. Anesthesia is administered using ketamine, acepromazine, diprivan, and sevoflurane. Care is taken to avoid any residual paralysis.

[0138] procedure: - A flexible 6-French quadrupole electrophysiology catheter is placed in the superior vena cava via the right femoral vein route. - A large, plate-shaped electrocautery electrode patch is placed on the right paravertebral line of the animal's back. The catheter electrodes 1 and 4 and the adhesive skin electrode patch are connected to an external pacemaker-type temporary pacemaker. Stimulation can be performed in bipolar mode at 12V x 3ms, frequency 60 / min. - The quality of stimulation of the right phrenic nerve can be objectively evaluated by performing diaphragmatic electromyography (EMG) of the right dome. Right diaphragmatic CMAP (compound muscle action potential) is recorded using a pair of skin electrodes (modified DI leads) placed 15 cm apart on the skin facing the right rib end. This recording is performed on an electrocardiograph with standard settings, i.e., 25 mm / sec and 10 mm / mV. CMAP measurement is performed on millimeter-sized ECG recording paper.

[0139] The operation is carried out in three phases.

[0140] Phase 1: Comparison of two stimulation modes, namely, stimulation using the prior art and stimulation using the present disclosure.

[0141] Under fluoroscopy, the catheter is positioned at 12 different locations at the level of the superior vena cava (SVC). Each position was evaluated by performing three types of fluoroscopy: frontal view, right anterior oblique view at 45°, and left anterior oblique view at 45°. The 12 different locations are uniformly distributed within the SVC (cranial-caudal / anterior-posterior / lateral-midline).

[0142] Without moving the catheter, perform the following operations at each site: - Conventional phrenic nerve stimulation, i.e., stimulation applied by an extended bipolar catheter between electrode 1 (anode) and electrode 4 (cathode) of the catheter. - Bipolar stimulation is applied between the distal electrode of the catheter (electrode 1 set as the anode) and the dorsal skin electrode patch (set as the cathode). - For each body part, the quality of diaphragm capture can be evaluated by measuring the amplitude of the diaphragmatic CMAP (measured in millimeters and collected in a spreadsheet).

[0143] Next, the catheter is moved to another site.

[0144] Phase 2: Evaluation of the effect of contact between the electrode and the SVC rear wall.

[0145] During bipolar stimulation between the distal electrode of the catheter and the dorsal skin electrode patch, the catheter is positioned sequentially as follows: - Floating in the lumen of blood vessels - Restless on the front wall - Restless on the back wall

[0146] The positions of the four catheters at the SVC level are evaluated.

[0147] The acquired CMAP measurements are organized in a spreadsheet.

[0148] Phase 3: Evaluation of the minimum size of the dorsal skin electrode patch.

[0149] The catheter is placed within the SVC. Bipolar stimulation is performed between the distal electrode of the catheter and the dorsal skin electrode patch.

[0150] At this position, the size of the dorsal skin patch is reduced by cutting the skin electrode patch, and the stimulation is tested. The patch is gradually removed in increments of 2 cm in length and 2 cm in width until the capture of the phrenic nerve by CMAP amplitude evaluation is incomplete. This procedure can be repeated by removing only the width without changing the length of the adhesive electrode.

[0151] In this way, the influence of the size of the skin electrode patch on the results can be determined.

[0152] result:

[0153] In experimental tests, the average CMAP at all tested locations was 2.5 mV from bipolar stimulation between the distal electrode of the catheter and the dorsal skin electrode patch. In contrast, the average CMAP for conventional stimulation with the catheter in extended bipolar mode was 1.8 mV.

[0154] The mean CMAP when using bipolar stimulation between the distal electrode of the catheter and the dorsal skin electrode patch was improved by up to 40% compared to the mean CMAP obtained using conventional stimulation.

[0155] Bipolar operation between the dorsal skin electrode patch and the intravascular electrode can be performed by reversing the polarity of the catheter electrode and the dorsal skin electrode patch. Reversing the polarity did not change the quality of the stimulation obtained and / or the amplitude of the CMAP.

[0156] Increasing the area of ​​the dorsal skin electrode patch appeared to be beneficial for CMAP amplitude.

[0157] Particularly favorable results were obtained when the catheter was stationary in either the anterior or posterior wall of the SVC and bipolar stimulation was performed.

[0158] Multiple electrode patch locations were tested. The right-sided position on the posterior paravertebral region had a similar effect to the position on the right side of the chest. On the other hand, the anterior position (i.e., the subject's chest) showed a reduced effect.

[0159] In certain embodiments, the distal portion of the catheter includes a spiral or spiral expandable portion configured to adhere circumferentially to the inner walls of the superior vena cava (VC), the right brachiocephalic vein, and / or the right subclavian vein, in order to remain in place during phrenic nerve stimulation.

[0160] The catheter may or may not further include a non-expandable distal end (or tip) located distal to the expandable portion. The distal end (if present) may be, for example, straight and / or have a length of 1 cm or more and / or 12 cm or less, for example, between 1.5 cm and 4 cm.

[0161] The expandable portion may have up to two turns of coil in its expanded configuration. In its expanded configuration, i.e., in its unrestricted expanded configuration, the expandable portion may have a diameter between 10 mm and 35 mm.

[0162] Furthermore, the catheter may be provided with a lumen for inserting a retractable straightened inner member. The catheter may further provide a straightened inner member within the lumen. The straightened inner member may be a guidewire. The guidewire may be made of metal, have a diameter of 0.030” or more and / or 0.040” or less, for example, equal to 0.032” or 0.035”, and / or be made of a hydrophobic material.

[0163] In the same implementation configuration, one or more intravascular electrodes may consist of multiple electrodes electrically connected to each other to form a single pole, or they may consist of multiple individual electrodes electrically disconnected from each other and capable of functioning as a single pole together.

[0164] Alternatively, the system may be configured to have multiple electrodes simultaneously deliver electrical pulses between each of the multiple electrodes and the external electrode patch. One or more intravascular electrodes may consist of, for example, 5 to 20 electrodes, or for example, 10 electrodes.

[0165] Figures 11-18 show examples of catheters 1100, 1200, 1300, 1400, 1500, 1600, 1700, and 1800 having expandable sections 1142, 1242, 1342, 1442, 1542, 1642, 1742, and 1842 in such configurations. As shown in Figures 13, 17, and 18, non-expandable distal ends 1350, 1750, and 1850 may be located distal to the expandable sections. Figure 16 shows a catheter 1600 with a 15 mm diameter expandable section 1642 positioned in the superior vena cava of a pig. Figure 17 shows a catheter 1700 with a 21 mm diameter expandable section 1742 and a straight, non-expandable distal end 1750 positioned in the superior vena cava of a pig. Figure 18 shows a catheter 1800 having an expandable portion 1842 with a diameter of 21 mm and a linear, non-expandable distal portion 1850.

[0166] This system implementation was experimentally tested on a 45 kg pig subject. The pig subject was given general anesthesia and placed in a supine position. Stimulation of the phrenic nerve was performed using an external electrode patch (cathode) placed on the right dorsal side of the animal and 10 electrodes (anodes) of a catheter in bipolar mode.

[0167] material: -032" hydrophobic rigid J-tip guidewire - 8F Introducer Tested prototypes:

[0168] [Table 1]

[0169] result:

[0170] [Table 2]

[0171] The prototype samples 1-5 listed in Tables 1 and 2 correspond to the expandable section samples shown in Figures 11-15, respectively. Performance is expressed on a 20-point scale, with 1 / 20 representing minimum performance and 20 / 20 representing maximum performance. Diaphragmatic stimulation was very good under all tested conditions. Sample 3, with its linear, non-expandable distal end, exhibited the best mechanical performance. The linearity of the non-expandable distal end facilitated the placement of the guide within the vena cava. Furthermore, even without the guide's assistance, placing, withdrawing, and repositioning the coil within the vena cava was very easy. Despite having a diameter of 21 mm (i.e., in its unrestricted expanded state), the coil remained horizontal and did not tilt.

Claims

1. A catheter (200, ..., 1000) comprising one or more intravascular electrodes (310, ..., 1010), wherein each of the intravascular electrodes is positioned on the distal portion (240, ..., 1040) of the catheter, For the purpose of introducing the catheter into the superior vena cava of a human patient, the distal end of the catheter is positioned within the superior vena cava (VC), the right brachiocephalic vein, and / or the right subclavian vein, and the extracorporeal electrode patch (260, 460) is configured to be attached to the patient opposite to the phrenic nerve, and is capable of operating in bipolar mode with one or more intravascular electrodes. A system for phrenic nerve stimulation equipped with [specific features / equipment].

2. The system according to claim 1, wherein the external electrode patch includes a conductive surface having a length greater than 1 cm and / or a width greater than 1 cm.

3. The system according to claim 2, wherein the conductive surface has a length of 4 cm or more and a width of 2 cm or more, such as a length greater than 8 cm and a width greater than 4 cm.

4. The system according to any one of claims 1 to 3, wherein the external electrode patch comprises a conductive layer made of a flexible and / or metallic material.

5. The system according to claim 4, wherein the conductive layer is a flexible metal layer.

6. The system according to any one of claims 1 to 5, wherein the external electrode patch includes a conductive adhesive coating.

7. The system according to any one of claims 1 to 6, wherein the distal portion of the catheter includes expandable portions (342, 541, ..., 1042), and the catheter has an expanded form.

8. The system according to claim 7, wherein the expandable portion is preferably configured to conform circumferentially to the inner wall of the superior vena cava (VC), the right brachiocephalic vein, and / or the right subclavian vein, so as to remain in a predetermined position during phrenic nerve stimulation.

9. The system according to claim 8, wherein one or more intravascular electrodes are at least partially arranged on the expandable portion.

10. The system according to claim 9, wherein at least one intravascular electrode is positioned on the expandable portion so as to contact the inner wall of the superior vena cava, the right brachiocephalic vein, and / or the right subclavian vein when the catheter is in the expanded portion.

11. The system according to claim 9 or 10, wherein, when in the expanded configuration, one or more intravascular electrodes are arranged on the circumference of the expandable portion.

12. The system according to any one of claims 7 to 11, wherein the extended embodiment is a helical or spiral configuration.

13. The system according to claim 12, wherein the expandable portion, when in the expanded state, forms a helix or spiral having at most two turns of coil.

14. The system according to any one of claims 7 to 11, wherein the extended embodiment is a loop-shaped, lasso-shaped, or basket-shaped configuration.

15. The system according to any one of claims 7 to 14, wherein the catheter has a non-expandable distal end after the expandable portion.

16. The system according to claim 15, wherein the non-expandable distal end is linear.

17. The system according to claim 15 or 16, wherein the length of the non-expandable distal end is greater than 1 cm and / or less than 12 cm, for example, between 1.5 cm and 4 cm.

18. The system according to any one of claims 7 to 17, wherein the expandable portion has a diameter between 10 mm and 35 mm when in the expanded state.

19. The system according to any one of claims 7 to 18, wherein the catheter comprises one or more pull wires that are operable to deform the catheter into the expanded form.

20. The system according to any one of claims 7 to 19, wherein the expandable portion is at least partially made of a shape memory material that biases the expandable portion to the expanded form.

21. The system according to any one of claims 1 to 20, wherein the catheter comprises a lumen for introducing a retractable linear inner member.

22. The catheter further comprises the linearized inner member within the lumen, according to claim 21.

23. The system according to claim 21 or 22, wherein the straightened inner member is a guide wire.

24. The system according to claim 23, wherein the guide wire is made of metal, and its diameter is greater than 0.020" and / or less than 0.060", preferably greater than 0.030" and / or less than 0.040", equal to, for example, 0.032" or 0.035", and / or made of a hydrophobic material.

25. The system according to any one of claims 1 to 24, further comprising one or more intravascular electrodes and an energy source (411) configured to conduct electricity with the extracorporeal electrode patch.

26. The system according to claim 25, wherein the energy source is configured to emit a plurality of electrical pulses, each having a voltage amplitude between 1V and 50V.

27. The system according to claim 25 or 26, wherein the energy source is configured to emit a plurality of electrical pulses, each having a duration between 0.1 ms and 20 ms.

28. The system according to any one of claims 1 to 27, wherein the one or more intravascular electrodes consist of a plurality of electrodes electrically connected to each other to form a monopole, or a plurality of individual electrodes, each electrically isolated from the others, that can function as a monopole collectively.

29. The system according to any one of claims 1 to 28, wherein the one or more intravascular electrodes consist of a plurality of electrodes, and the system is configured to operate the plurality of electrodes so as to simultaneously deliver an electrical pulse between each individual electrode of the plurality of electrodes and the extracorporeal electrode patch.

30. The system according to any one of claims 1 to 29, wherein the one or more intravascular electrodes consist of between 5 and 20 electrodes, for example, 10 electrodes.

31. The system according to any one of claims 1 to 30, further comprising units (490-494) for monitoring the response of the diaphragm to phrenic nerve stimulation.

32. A system for cardiac cryoablation comprising the system according to any one of claims 1 to 31, and a cryoablation catheter (480).

33. A system according to any one of claims 1 to 31, or a system according to claim 32, For example, instructions regarding phrenic nerve stimulation in human patients, such as during cardiac cryoablation, Optionally, instructions to monitor the diaphragmatic response to phrenic nerve stimulation, and / or instructions to perform cardiac cryoablation. A kit for phrenic nerve stimulation and / or cardiac cryoablation, including [specific components / methods].

34. A computer program comprising executable code for operating one or more intravascular electrodes and an energy source electrically conductive to the extracorporeal electrode patch of the stimulation system according to any one of claims 1 to 31.

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