Treatment of cardiac tissue using pulsed electric fields

Abstract

Devices, systems, and methods are provided for treating conditions of the heart, particularly the occurrence of arrhythmias. The devices, systems, and methods deliver therapeutic energy to portions of the heart, such as to the pulmonary vein ostia when treating atrial fibrillation, to provide tissue modification. Generally, the tissue modification systems include a specialized catheter, a high voltage waveform generator, and at least one different energy delivery algorithm. Other embodiments include conventional ablation catheter and system components to support use with the high voltage waveform generator. Example catheter designs include a variety of delivery types, including localized delivery, "single shot" delivery, and various combinations thereof. In some embodiments, energy is delivered in a monopolar fashion. However, it will be appreciated that a variety of other embodiments are also provided.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority and benefit to U.S. Patent Application No. 62 / 949,633, filed December 18, 2019, entitled “Treatment of Cardiac Tissue with Pulsed Electric Fields”; U.S. Patent Application No. 63 / 000,275, filed March 26, 2020, entitled “Treatment of Cardiac Tissue with Pulsed Electric Fields”; and U.S. Patent Application No. 63 / 083,644, filed September 25, 2020, entitled “Interface Connector For Use in Pulsed Electric Field Procedures”.

[0003] For all purposes, the disclosure of the aforementioned application is incorporated herein by reference in its entirety. Background Technology

[0004] Treatment energy can be applied to the heart and vascular system to treat a variety of conditions, including atherosclerosis (particularly in restenosis prevention after angioplasty) and arrhythmias such as atrial fibrillation (AF). AF is the most common persistent arrhythmia and significantly increases the risk of death in affected patients, particularly by causing stroke. In this phenomenon, the heart deviates from its normal sinus rhythm due to the generation of erroneous electrical impulses. AF is thought to originate in the myocardial sleeve of the pulmonary vein (PV) due to the presence of automaticity in the cells within the myocardial tissue. Pacing activity from these cells is thought to lead to the formation of ectopic beats, thus triggering AF. The PV is also considered to play a crucial role in maintaining AF because the disordered structure and electrophysiological properties of these vessels provide an environment in which AF can persist. Therefore, disrupting or removing these abnormal pacemaker cells within the myocardial sleeve of the PV is a target, and AF is typically treated by delivering therapeutic energy to the pulmonary vein. However, due to reports of PV stenosis, this approach has routinely been modified to target the PV sinus to achieve conduction block between the PV and the left atrium. In addition to the pulmonary veins, the PV sinus also includes the roof and posterior wall of the left atrium, and in the case of the right pulmonary vein sinus, a portion of the atrial septum. In some cases, this technique offers a higher success rate and a lower complication rate compared to pulmonary vein ostium isolation.

[0005] Thermal ablation therapy, particularly radiofrequency (RF) ablation, is currently the "gold standard" for treating symptomatic atrial fibrillation through localized tissue necrosis. Typically, RF ablation creates a ring of ablation foci around the opening of each of the four pulmonary veins. The RF current causes tissue drying by creating a localized thermal zone that leads to discrete coagulative necrosis. The necrotic tissue acts as a conduction blocker, thereby isolating the veins.

[0006] While existing methods have improved sinus rhythm reconstruction, success rates and safety remain limited. RF ablation continues to face several limitations, including: long procedure times for pulmonary vein isolation using local RF catheters; difficulty in creating and confirming transmural ablation foci due to potential gaps in the ablation pattern caused by point-by-point ablation techniques using conventional RF catheters; the formation of carbon and / or gas at the catheter tip-tissue interface due to high temperatures, which may lead to thrombi or emboli during ablation; and thermal damage to collateral extracardiac structures, including pulmonary vein stenosis, phrenic nerve injury, esophageal injury, atrial-esophageal fistula, periesophageal vagal nerve injury, perforation, thromboembolic events, vascular complications, and acute coronary artery obstruction. These limitations are primarily attributed to the ongoing challenge for clinicians in balancing effective therapeutic doses with inappropriate energy delivery to extracardiac tissues.

[0007] Therefore, while maintaining this technology in clinical practice, safer and more versatile methods for removing abnormal tissue have been used, including irreversible electroporation (IRE)—a non-thermal therapy based on irreversible permeation of the cell membrane caused by specific short pulses of high voltage energy. IRE has been found to be tissue-specific, inducing apoptosis rather than necrosis, and safer for structures adjacent to the myocardium. However, the success of these IRE methods has been inconsistent to date. In some cases, the delivery of IRE energy results in incomplete blockage of the abnormal electrical rhythm. This can be due to a variety of factors, such as irregularities in circumferential treatment around the pulmonary veins, insufficient transmural energy delivery, or other defects in energy delivery. In any case, atrial fibrillation is not adequately treated, or it recurs later. Therefore, there is a need to improve the management of atrial fibrillation. Such management should be safe, effective, and reduce complications. The systems, devices, and methods described herein will meet at least some of these objectives. Summary of the Invention

[0008] This document describes embodiments of apparatus, systems, and methods for processing target tissues, particularly cardiac tissue. Similarly, the invention relates to the following numbered clauses:

[0009] 1. A system for processing a patient's cardiac tissue, comprising:

[0010] Treatment catheter, which has a delivery electrode; and

[0011] A generator electrically coupled to the processing conduit, wherein the generator includes at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy that can be delivered through the delivery electrodes.

[0012] The processing catheter and the generator are configured to deliver the pulsed electric field energy unipolarly through the heart tissue to a remote return electrode.

[0013] 2. The system of claim 1, wherein the delivery electrode has a cylindrical shape and is configured to be positioned against the distal side of the heart tissue.

[0014] 3. The system of claim 2, wherein the distal side has a single continuous surface.

[0015] 4. The system according to any one of the preceding claims, wherein the delivery electrode includes a distal side having a contact surface configured to be positioned against the cardiac tissue.

[0016] 5. The system according to claim 4, wherein the contact surface has a circular shape and a diameter of 2-3 mm.

[0017] 6. The system according to claim 4, wherein the contact surface has a thickness of 3-8 mm. 2 Surface area.

[0018] 7. The system of claim 4, wherein the contact surface is configured to have a current density of 2 amperes per square millimeter when delivering 15 joules of pulsed electric field energy.

[0019] 8. The system according to any one of the preceding claims, wherein the electrical signal of the pulsed electric field energy has a voltage of at least 2000V.

[0020] 9. The system according to any one of the preceding claims, wherein the electrical signal comprises a biphasic pulse wave packet.

[0021] 10. The system according to any one of the preceding claims, wherein the generator is configured to receive a measurement of the depth of the cardiac tissue and to select one of the at least one energy delivery algorithms based on the measurement of the depth.

[0022] 11. The system according to any one of the preceding claims, wherein the generator is configured to receive a measurement of the depth of the cardiac tissue and to select one of the at least one energy delivery algorithms, the energy delivery algorithm being provided to provide energy that is believed to create a non-thermal lesion having a depth exceeding the measurement of the depth of the cardiac tissue.

[0023] 12. The system according to any one of claims 10-11, wherein the depth measurement is received from the imaging instrument.

[0024] 13. The system according to any one of claims 10-11, wherein the depth measurement is received from the data input.

[0025] 14. The system according to any one of the preceding claims, wherein the delivery electrode and the electrical signal are configured such that the pulsed electric field energy delivered to the heart tissue via the delivery electrode creates a non-thermal lesion in the heart tissue at a depth of at least 4 mm as a result of delivering up to 30 joules of pulsed electric field energy thereon.

[0026] 15. The system according to any one of the preceding claims, wherein the delivery electrode and the electrical signal are configured such that the pulsed electric field energy delivered to the cardiac tissue via the delivery electrode creates a non-thermal lesion in the cardiac tissue at a depth of at least 7 mm as a result of delivering up to 400 joules of pulsed electric field energy thereon.

[0027] 16. The system according to any one of the preceding claims, wherein the cardiac tissue is located near an extracardiac structure, wherein the delivery electrode and the electrical signal are configured such that the pulsed electric field energy delivered through the cardiac tissue to a remote electrode assists in preventing thermal damage to the extracardiac structure.

[0028] 17. The system according to any one of the preceding claims, wherein the cardiac tissue includes the tricuspid isthmus, and wherein the electrical signal is configured such that the pulsed electric field energy delivered to the tricuspid isthmus through the delivery electrode creates a non-thermal lesion of at least 10 mm depth.

[0029] 18. The catheter according to any one of the preceding claims, wherein the cardiac tissue comprises a ventricle, and wherein the electrical signal is configured such that the pulsed electric field energy delivered to the ventricle via the delivery electrode creates a non-thermal lesion of at least 7 mm depth as a result of the delivery of the pulsed electric field energy.

[0030] 19. The catheter according to any one of the preceding claims, wherein the cardiac tissue comprises the anterior wall of the heart, and wherein the electrical signal is configured such that the pulsed electric field energy delivered to the anterior wall through the delivery electrode creates a non-thermal lesion of at least 5 mm depth.

[0031] 20. The system according to any one of the preceding claims further includes a cardiac monitor for measuring a patient's heart rate per minute, wherein the generator is configured to modify energy delivery based on at least one measurement of the heart rate per minute.

[0032] 21. The system of claim 20, wherein the generator is configured to stop energy delivery if at least one measurement of the heart rate per minute is at or below a predetermined threshold.

[0033] 22. The system of claim 21, wherein the predetermined threshold is 30 heartbeats per minute.

[0034] 23. The system according to any one of claims 20-22, wherein the generator is configured to provide energy delivery at a lower frequency if at least one measurement of the heart rate per minute is at or above a predetermined threshold.

[0035] 24. The system of claim 23, wherein the lower frequency is included during every other heartbeat.

[0036] 25. The system according to any one of claims 23-24, wherein the predetermined threshold is 120 heartbeats per minute.

[0037] 26. The system according to any one of the preceding claims further includes a temperature sensor, wherein the generator is configured to modify energy delivery based on at least one measurement from the temperature sensor.

[0038] 27. The system of claim 26, wherein modifying energy delivery includes providing energy delivery at a lower frequency if the at least one measurement from the temperature sensor is at or above a predetermined threshold.

[0039] 28. The system of claim 27, wherein the lower frequency is included during every other heartbeat.

[0040] 29. The system according to any one of claims 27-28, wherein the predetermined threshold is 65°C.

[0041] 30. The system according to any one of claims 26-29, wherein the at least one measurement includes a series of measurements indicating a rapid increase in temperature.

[0042] 31. The system of claim 30, wherein the rapid temperature rise comprises a change of 3-5 degrees Celsius throughout the heartbeat.

[0043] 32. The system according to any one of claims 26-31, wherein the treatment conduit further comprises at least one irrigation port, and the system further comprises an irrigation pump, wherein the irrigation pump is configured to modify the delivery of irrigation fluid through the irrigation pump based on the at least one measurement from the temperature sensor.

[0044] 33. The system according to any one of the preceding claims further includes a contact sensor, wherein the generator is configured to modify at least one energy delivery algorithm in the at least one energy delivery algorithm based on at least one measurement from the contact sensor.

[0045] 34. The system according to any one of the preceding claims further includes a contact force sensor, wherein the generator is configured to modify at least one energy delivery algorithm in the at least one energy delivery algorithm based on at least one measurement from the contact force sensor.

[0046] 35. A system for creating a lesion in a region of a patient's cardiac tissue, comprising:

[0047] Treatment catheter, which has a delivery electrode; and

[0048] A generator electrically coupled to the treatment catheter, wherein the generator includes at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through the delivery electrode to create the lesion in the cardiac tissue, wherein the lesion has sufficient depth to block the electrical signal through the cardiac tissue region.

[0049] 36. The system of claim 35, wherein the electrical signal comprises a series of biphase pulses.

[0050] 37. The system of claim 36, wherein the series of biphase pulses is delivered in the form of multiple wave packets.

[0051] 38. The system of claim 37, wherein each of the plurality of wave packets comprises 30-45 biphasic pulses.

[0052] 39. The system according to any one of claims 37-38, wherein the plurality of wave packets are delivered in the form of a plurality of bundles, wherein each bundle is delivered between predetermined portions of each heartbeat.

[0053] 40. The system of claim 39, wherein the predetermined portion comprises a T-wave.

[0054] 41. The system according to any one of claims 39-40, wherein each beam comprises 1-3 wave packets.

[0055] 42. The system of claim 41, wherein 10-30 wave packets are delivered to create the lesion.

[0056] 43. The system according to any one of claims 35-42, wherein the delivery electrode has a cylindrical shape and a distal side configured to be positioned against the cardiac tissue region.

[0057] 44. The system of claim 43, wherein the distal side has a single continuous surface.

[0058] 45. The system according to any one of claims 35-44, wherein the delivery electrode includes a distal side having a contact surface configured to be positioned against the cardiac tissue region.

[0059] 46. ​​The system according to any one of claims 35-45, wherein the processing catheter and the generator are configured to deliver the pulsed electric field energy unipolarly through the cardiac tissue region to a remote return electrode.

[0060] 47. The system according to any one of claims 35-46, wherein the cardiac tissue region includes pulmonary veins, and wherein the depth is sufficient to block conduction between the pulmonary veins and the rest of the heart.

[0061] 48. A catheter for treating a region of cardiac tissue, comprising:

[0062] A shaft having a longitudinal axis; and

[0063] A delivery electrode having conductive edges extending around the longitudinal axis, wherein the continuous edges have a closed shape configured to engage with the opening of a pulmonary vein to create a continuous lesion around the opening of the pulmonary vein.

[0064] 49. The catheter of claim 48, wherein the delivery electrode comprises one or more rings, wherein a portion of the ring forms the conductive edge.

[0065] 50. The catheter of claim 49, wherein the one or more loops are composed of wires.

[0066] 51. The catheter according to any one of claims 48-50, wherein the continuous edge forms a closed shape with an adjustable diameter.

[0067] 52. The catheter of claim 51, wherein the adjustable diameter can be adjusted by pressing the continuous edges against the cardiac tissue region to move the one or more loops relative to each other.

[0068] 53. The catheter of claim 52, wherein the movement relative to each other includes a change in the overlap of at least two portions of the one or more loops.

[0069] 54. The catheter of claim 48, wherein the delivery electrode has a funnel-shaped shape extending outward from the longitudinal axis of the shaft, wherein the conductive edge extends around the opening of the funnel-shaped shape.

[0070] 55. The catheter of claim 54, wherein the continuous edge forms a closed shape with adjustable thickness.

[0071] 56. The catheter of claim 55, wherein the adjustable thickness can be adjusted by pressing the funnel-shaped nozzle against the cardiac tissue region.

[0072] 57. The catheter of claim 56, wherein the delivery electrode comprises a plurality of wires, and wherein pressing the funnel-shaped nozzle against the cardiac tissue region pulls at least a portion of the plurality of wires together.

[0073] 58. The catheter according to any one of claims 48-57, wherein the delivery electrode comprises at least two electrodes that can be individually energized.

[0074] 59. The catheter according to any one of claims 48-58, wherein the delivery electrode is configured to unipolarly deliver energy through the heart tissue to a remote return electrode.

[0075] 60. A subsystem for use with a catheter configured to be connected to a signal generator, wherein the catheter includes a catheter body comprising a distal portion and a proximal portion, the distal portion of the catheter body including a plurality of electrodes electrically isolated from each other, the proximal portion of the catheter body including a plurality of terminals and configured to be connected to a signal generator such that stimulation energy can be delivered via selected one or more electrodes, and the catheter further including a plurality of conductive wires, wherein each conductive wire electrically couples a different electrode of the electrodes to a corresponding different terminal of the terminals, the subsystem comprising:

[0076] A component network configured to maintain the potential difference between one or more electrodes of the catheter selected for delivering stimulation energy and one or more other electrodes of the catheter not selected for delivering stimulation energy below a threshold potential difference that prevents arcing between one or more pairs of conductive wires.

[0077] 61. The subsystem of claim 60, wherein the component network comprises a plurality of resistors.

[0078] 62. The subsystem of claim 61, wherein each of the plurality of resistors is disposed between a conductive wire electrically coupled to an electrode selected for delivering stimulation energy and a conductive wire electrically coupled to an electrode not selected for delivering stimulation energy.

[0079] 63. The subsystem of claim 62, wherein the plurality of electrodes comprises one electrode selected for delivering stimulation energy and three electrodes not selected for delivering stimulation energy, and wherein the plurality of resistors comprises

[0080] A first resistor is disposed between a delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and a first conductive wire electrically coupled to the first of the three electrodes not selected for delivering stimulation energy.

[0081] A second resistor is disposed between the delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and a second conductive wire electrically coupled to the second of the three electrodes not selected for delivering stimulation energy.

[0082] A third resistor is disposed between the delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and the third conductive wire electrically coupled to the third of the three electrodes not selected for delivering stimulation energy.

[0083] 64. The subsystem of claim 63, wherein the first resistor has a resistance value of 500 ohms, the second resistor has a resistance value of 300 ohms, and the third resistor has a resistance value of 300 ohms.

[0084] 65. The subsystem according to any one of claims 63-64, wherein the total resistance network combination of the first resistor, the second resistor, and the third resistor has a maximum value of 1000 to 1200 ohms.

[0085] 66. The subsystem of claim 60, wherein the component network comprises at least one resistor, inductor, or diode.

[0086] 67. The subsystem of claim 66, wherein at least one value of the at least one resistor, inductor, or diode is selectable.

[0087] 68. The subsystem of claim 67 further includes an algorithm for determining the at least one value based on information provided by the user.

[0088] 69. The subsystem of claim 68, wherein the algorithm includes a three-dimensional mathematical model of the current distribution from the conduit.

[0089] 70. The subsystem according to any one of claims 68-69, wherein the information provided by the user includes the voltage, frequency, or amplitude of the energy.

[0090] 71. The subsystem according to any one of claims 68-70, wherein the user-provided information includes the number of electrodes, the size of the electrodes, the distance between the electrodes, the brand of the catheter, the model of the catheter, and / or the type of energy the catheter is designed for.

[0091] 72. The subsystem according to any one of claims 68-71, wherein the user-provided information includes target tissue type, target cell type, conductivity, impedance, temperature, irrigation status and / or anatomical location.

[0092] 73. The subsystem according to any one of claims 60-72, wherein the threshold potential difference is less than or equal to 1000-1500 volts.

[0093] 74. The subsystem according to any one of claims 60-73, wherein the total current through the component network is below a predetermined threshold current level.

[0094] 75. The subsystem of claim 74, wherein the predetermined threshold current level is 40 amperes.

[0095] 76. The subsystem according to any one of claims 60-75, wherein the subsystem is configured to be connected between the signal generator and the conduit.

[0096] 77. The subsystem according to any one of claims 60-75, wherein the subsystem is part of the signal generator.

[0097] 78. The subsystem according to any one of claims 60-75, wherein the subsystem is part of the conduit.

[0098] 79. The subsystem according to any one of claims 60-78, wherein the conduit is configured to prevent arcing between one or more pairs of the conductive wires when receiving stimulation energy having a voltage up to a predetermined voltage level, and wherein the stimulation energy delivered by the signal generator includes energy exceeding the predetermined voltage level, wherein the subsystem prevents arcing between one or more pairs of conductive wires.

[0099] 80. The subsystem of claim 79, wherein the predetermined voltage level comprises 1000-1500 volts.

[0100] 81. The subsystem according to any one of claims 60-80, wherein the catheter comprises a radiofrequency ablation catheter.

[0101] 82. The subsystem of claim 81, wherein the stimulation energy comprises pulsed electric field energy.

[0102] 83. The subsystem according to any one of claims 81-82, wherein the stimulation energy has a voltage of at least 2000V.

[0103] 84. A system for adapting a conduit having a plurality of electrically isolated electrodes, wherein at least one of the plurality of electrodes is selectable for delivering stimulation energy, and wherein the conduit includes a plurality of conductive wires, wherein each conductive wire is electrically coupled to a different electrode of the electrodes, the system comprising:

[0104] A component network configured to increase the current threshold for arc discharge between one or more pairs of conductive wires.

[0105] 85. The system of claim 84, wherein the component network comprises a plurality of resistors.

[0106] 86. The system of claim 85, wherein each of the plurality of resistors is disposed between a conductive wire electrically coupled to an electrode selected for delivering stimulation energy and a conductive wire electrically coupled to an electrode not selected for delivering stimulation energy.

[0107] 87. The system of claim 86, wherein the plurality of electrodes comprises one electrode selected for delivering stimulation energy and three electrodes not selected for delivering stimulation energy, and wherein the plurality of resistors comprises

[0108] A first resistor is disposed between a delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and a first conductive wire electrically coupled to the first of the three electrodes not selected for delivering stimulation energy.

[0109] A second resistor is disposed between the delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and a second conductive wire electrically coupled to the second of the three electrodes not selected for delivering stimulation energy.

[0110] A third resistor is disposed between the delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and the third conductive wire electrically coupled to the third of the three electrodes not selected for delivering stimulation energy.

[0111] 88. The system of claim 87, wherein the first resistor has a resistance value of 500 ohms, the second resistor has a resistance value of 300 ohms, and the third resistor has a resistance value of 300 ohms.

[0112] 89. The system according to any one of claims 87-88, wherein the total resistance network combination of the first resistor, the second resistor and the third resistor has a maximum value of 1000 to 1200 ohms.

[0113] 90. The system of claim 84, wherein the component network comprises at least one resistor, inductor, or diode.

[0114] 91. The system of claim 90, wherein at least one value of the at least one resistor, inductor, or diode is selectable.

[0115] 92. The system of claim 91 further includes an algorithm for determining the at least one value based on information provided by the user.

[0116] 93. The system of claim 92, wherein the algorithm comprises a three-dimensional mathematical model of the current distribution from the conduit.

[0117] 94. The system according to any one of claims 92-93, wherein the information provided by the user includes the voltage, frequency, or amplitude of the energy.

[0118] 95. The system according to any one of claims 92-94, wherein the information provided by the user includes the number of electrodes, the size of the electrodes, the distance between the electrodes, the brand of the catheter, the model of the catheter, and / or the type of energy the catheter is designed for.

[0119] 96. The system according to any one of claims 92-95, wherein the user-provided information includes target tissue type, target cell type, conductivity, impedance, temperature, irrigation status, and / or anatomical location.

[0120] 97. The system according to any one of claims 84-96, wherein the current threshold of the arc discharge is 40 amperes.

[0121] 98. The system according to any one of claims 84-97, wherein the system is configured to be connected between the signal generator and the conduit.

[0122] 99. The system according to any one of claims 84-97, wherein the system is part of the signal generator.

[0123] 100. The system according to any one of claims 84-97, wherein the system is part of the catheter.

[0124] 101. The system according to any one of claims 84-100, wherein the catheter comprises a radiofrequency ablation catheter.

[0125] 102. The system according to any one of claims 84-100, wherein the catheter comprises a microwave ablation catheter.

[0126] 103. The system according to any one of claims 84-102, wherein the stimulation energy comprises pulsed electric field energy.

[0127] 104. The system of claim 103, wherein the stimulation energy has a voltage of at least 2000V.

[0128] 105. A system for adapting a catheter that fails at least partially when receiving stimulation energy having a voltage or current exceeding a threshold level, the system comprising:

[0129] A component network that can be coupled to the conduit, wherein the component network amplifies the threshold level to a higher threshold level.

[0130] 106. The system of claim 105, wherein the conduit comprises a dielectric material, and wherein at least partial failure comprises breakdown of the dielectric material.

[0131] 107. The system of claim 105, wherein the conduit comprises a wire insulated by an insulating material, and wherein at least partial failure comprises a breakdown of the insulating material.

[0132] 108. The system according to any one of claims 105-107, wherein the higher threshold level is at least 20% greater than the threshold level.

[0133] 109. The system of claim 108, wherein the higher threshold level is at least 40% greater than the threshold level.

[0134] 110. The system according to any one of claims 105-109, wherein the catheter is configured to receive stimulation energy comprising radio frequency or microwave energy, and the component network is adapted to the catheter to receive stimulation energy comprising high voltage energy.

[0135] 111. The system of claim 110, wherein the high voltage energy includes pulsed electric field energy, irreversible electroporation energy, pulsed radio frequency ablation, or nanosecond pulsed electric field energy.

[0136] 112. The system according to any one of claims 105-111, wherein the conduit fails at least partially due to arcing between one or more pairs of conductive wires when receiving stimulation energy having a voltage or current higher than a threshold level, wherein the component network prevents arcing between the one or more pairs of conductive wires when receiving stimulation energy having a voltage or current higher than the threshold level and lower than the higher threshold level.

[0137] 113. The system according to any one of claims 105-112, wherein when receiving stimulation energy having a voltage or current higher than the threshold level and lower than a higher threshold level, the component network maintains that the potential difference between one or more pairs of conductive wires does not exceed the potential difference threshold.

[0138] 114. The system of claim 113, wherein the potential difference threshold is 1000-1500 volts.

[0139] 115. The system of claim 113, wherein the potential difference threshold is 1000 volts.

[0140] 116. The system according to any one of claims 105-115, wherein the component network comprises resistors, inductors, or diodes.

[0141] 117. The system of claim 116, wherein the component network comprises a plurality of resistors, and wherein each of the plurality of resistors is disposed between a conductive wire electrically coupled to an electrode selected for delivering stimulation energy and a conductive wire electrically coupled to an electrode not selected for delivering stimulation energy.

[0142] 118. The system of claim 117, wherein the plurality of electrodes comprises one electrode selected for delivering stimulation energy and three electrodes not selected for delivering stimulation energy, and wherein the plurality of resistors comprises

[0143] A first resistor is disposed between a delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and a first conductive wire electrically coupled to the first of the three electrodes not selected for delivering stimulation energy.

[0144] A second resistor is disposed between the delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and a second conductive wire electrically coupled to the second of the three electrodes not selected for delivering stimulation energy.

[0145] A third resistor is disposed between the delivery conductive wire electrically coupled to the electrode selected for delivering stimulation energy and the third conductive wire electrically coupled to the third of the three electrodes not selected for delivering stimulation energy.

[0146] 119. The system of claim 118, wherein the first resistor has a resistance value of 500 ohms, the second resistor has a resistance value of 300 ohms, and the third resistor has a resistance value of 300 ohms.

[0147] 120. The system according to any one of claims 118-119, wherein the total resistance network combination of the first resistor, the second resistor and the third resistor has a maximum value of 1000 to 1200 ohms.

[0148] 121. The system of claim 116, wherein at least one value of the at least one resistor, inductor, or diode is selectable.

[0149] 122. The system of claim 121 further includes an algorithm for determining the at least one value based on information provided by the user.

[0150] 123. The system of claim 122, wherein the algorithm comprises a three-dimensional mathematical model of the current distribution from the conduit.

[0151] 124. The system according to any one of claims 122-123, wherein the information provided by the user includes the voltage, frequency, or amplitude of the energy.

[0152] 125. The system according to any one of claims 122-124, wherein the user-provided information includes the number of electrodes, the size of the electrodes, the distance between the electrodes, the brand of the catheter, the model of the catheter, and / or the type of energy the catheter is designed for.

[0153] 126. The system according to any one of claims 122-125, wherein the user-provided information includes target tissue type, target cell type, conductivity, impedance, temperature, irrigation status and / or anatomical location.

[0154] 127. The system according to any one of claims 105-126 further includes a high-voltage generator that generates stimulation energy having a voltage or current higher than the threshold level.

[0155] 128. The system of claim 127, wherein the component network is disposed within the generator.

[0156] 129. The system according to any one of claims 105-128, wherein the component network comprises one or more potentiometers, rheostats, or variable resistors.

[0157] 130. The system according to any one of claims 105-129, wherein the component network comprises one or more capacitors, inductors, or diodes.

[0158] 131. The system according to any one of claims 105-130, wherein the catheter comprises a radiofrequency ablation catheter or a microwave catheter.

[0159] 132. The system according to any one of claims 105-131, wherein the stimulation energy comprises pulsed electric field energy.

[0160] 133. The system of claim 132, wherein the stimulation energy has a voltage of at least 2000V.

[0161] 134. A system comprising:

[0162] A catheter having a delivery electrode, wherein the catheter is configured to deliver thermal ablation energy; and

[0163] A generator electrically coupled to the processing conduit, wherein the generator includes at least one energy delivery algorithm configured to provide an electrical signal of non-thermal high-voltage energy that can be delivered through the delivery electrode.

[0164] 135. The system of claim 134, wherein the thermal ablation energy includes radiofrequency ablation energy.

[0165] 136. The system of claim 134, wherein the thermal ablation energy comprises a microwave ablation frequency.

[0166] 137. The system according to any one of claims 134-136, wherein the high voltage energy comprises pulsed electric field energy.

[0167] 138. The system according to any one of claims 134-137, wherein the high voltage energy includes irreversible electroporation energy, pulsed radio frequency ablation, or nanosecond pulsed electric field energy.

[0168] 139. The system according to any one of claims 134-138, wherein the high-voltage energy has a voltage of at least 2000V.

[0169] 140. The system according to any one of claims 134-139, wherein the high-voltage energy comprises an electrical signal having biphase pulse packets.

[0170] 141. The system according to any one of claims 134-140, wherein the processing catheter and the generator are configured to deliver the pulsed electric field energy unipolarly through the tissue to a remote return electrode.

[0171] 142. The system according to any one of claims 134-141, wherein the generator is configured to receive a measurement of the depth of the tissue and to select one of the at least one energy delivery algorithms, the energy delivery algorithm providing energy believed to create a non-thermal lesion having a depth exceeding the measurement of the depth of the tissue.

[0172] 143. The system of claim 142, wherein the tissue comprises heart tissue.

[0173] 144. The system according to any one of claims 134-143, further comprising a component network that can be coupled to the conduit, wherein the component network is configured to increase the current threshold for arc discharge between one or more pairs of conductive wires within the conduit.

[0174] 145. The system of claim 144, wherein the component network comprises a plurality of resistors.

[0175] 146. The system of claim 145, wherein the conduit further comprises at least one electrode not selected for delivering stimulation energy, wherein each of the plurality of resistors is disposed between a conductive wire electrically coupled to the delivery electrode and a conductive wire electrically coupled to one of the electrodes not selected for delivering stimulation energy.

[0176] 147. The system according to any one of claims 134-146 further includes an electroanatomical mapping system electrically coupled to the treatment catheter.

[0177] 148. The system of claim 147 further includes an interface connector that electrically couples the catheter to both the generator and the electroanatomical mapping system, wherein the interface connector prevents the delivery electrode from being electrically connected to both the generator and the electroanatomical mapping system simultaneously.

[0178] 149. The system of claim 148, wherein the interface connector includes a switching system comprising a first path of at least one wire between the delivery electrode and the generator and a second path of at least one wire between the delivery electrode and the electroanatomical mapping system, wherein the switching system switches energy transfer between the first path and the second path.

[0179] 150. The system of claim 149, wherein the switching system performs switching by selectively opening and closing one or more switches.

[0180] 151. The system according to any one of claims 134-150, further comprising a module electrically coupled to the processing catheter.

[0181] 152. The system of claim 151, wherein the conduit includes a thermocouple, and wherein the module includes components for temperature monitoring.

[0182] 153. The system according to any one of claims 151-152, wherein the conduit includes a contact sensor, and wherein the module includes components for monitoring contact.

[0183] 154. The system according to any one of claims 151-153, wherein the conduit includes a contact force sensor, and wherein the module includes components for monitoring contact force.

[0184] 155. The system according to any one of claims 134-154, further comprising an external cardiac monitor electrically coupled to the generator.

[0185] 156. The system according to any one of claims 134-155 further includes an external return electrode electrically coupled to the generator.

[0186] 157. A system for processing a patient's cardiac tissue, comprising:

[0187] A processing catheter having at least one contact element;

[0188] A generator electrically coupled to the processing conduit, wherein the generator includes at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through at least one of the at least one contacts; and

[0189] An interface connector electrically couples the at least one contact to both the generator and the electroanatomical mapping system, wherein the interface connector prevents the at least one contact from being electrically connected to both the generator and the electroanatomical mapping system simultaneously.

[0190] 158. The system of claim 157, wherein the interface connector includes a switching system comprising a first path of at least one wire between the at least one contact and the generator and a second path of at least one wire between the at least one contact and the electroanatomical mapping system, wherein the switching system switches energy transfer between the first path and the second path.

[0191] 159. The system of claim 158, wherein the switching system performs switching by selectively opening and closing one or more switches.

[0192] 160. The system of claim 159, wherein at least one of the one or more switches comprises a high-voltage relay.

[0193] 161. The system of claim 159, wherein at least one of the one or more switches can be turned on while at least one of the one or more switches is turned off.

[0194] 162. The system of claim 159, wherein at least one of the one or more switches can be closed while at least one of the one or more switches is open.

[0195] 163. The system according to any one of claims 157-162, wherein at least one of the at least one contact senses the input signal.

[0196] 164. The system of claim 163, wherein the input signal includes a cardiac mapping signal or an electrocardiogram.

[0197] 165. The system according to any one of claims 157-163, wherein the at least one contact comprises a plurality of contacts, and wherein the interface connector comprises a separate electrical terminal corresponding to each of the plurality of contacts.

[0198] 166. The system according to any one of claims 157-165, wherein the at least one contact comprises a plurality of electrodes electrically isolated from each other, and wherein at least one of the plurality of electrodes is selectable for the delivery of stimulating energy.

[0199] 167. The system of claim 166, wherein the conduit comprises a plurality of conductive wires, wherein each conductive wire is electrically coupled to a different electrode among the plurality of electrodes, and the interface connector further comprises a component network configured to increase the current threshold for arc discharge between one or more pairs of the conductive wires.

[0200] 168. The system of claim 166, wherein the component network is configured to maintain a potential difference between the one or more pairs of conductive wires.

[0201] 169. The system according to any one of claims 157-168, wherein the at least one contact comprises a thermocouple electrically coupled to the electroanatomical mapping system.

[0202] 170. The system according to any one of claims 157-168, wherein the at least one contact comprises a thermocouple electrically coupled to a module including components for temperature monitoring.

[0203] 171. The system of claim 170, wherein the thermocouple is electrically connected to the module independently of the communication between the conduit and the generator or between the conduit and the electroanatomical mapping system.

[0204] 172. The system according to any one of claims 157-171, wherein the at least one contact comprises a contact sensor or a contact force sensor, the contact sensor or contact force sensor being electrically coupled to the electroanatomical mapping system.

[0205] 173. The system according to any one of claims 157-171, wherein the at least one contact comprises a contact sensor or a contact force sensor, the contact sensor or contact force sensor being electrically coupled to a module comprising components for contact sensing or contact force sensing.

[0206] 174. The system of claim 173, wherein the contact sensor or contact force sensor is electrically connected to the module independently of the communication between the catheter and the generator or between the catheter and the electroanatomical mapping system.

[0207] 175. The system according to any one of claims 157-174, wherein the processing conduit is configured to deliver the pulsed electric field energy in a unipolar manner.

[0208] 176. The system of claim 175, wherein the interface connector electrically couples the generator to a return electrode configured to be located remotely from the processing conduit.

[0209] 177. The system of claim 175 further includes a return electrode configured to be located remotely from the processing conduit.

[0210] 178. An interface connector, comprising:

[0211] A first port is used for electrical connection to a conduit having at least one contact, wherein the first port includes a separate electrical terminal corresponding to each of the at least one contact;

[0212] The second port is used to electrically connect the generator to one or more of the at least one contact to deliver high-voltage energy therethrough.

[0213] A third port is used to electrically connect an external device to one or more of the at least one contact to transmit low-voltage energy therebetween; and

[0214] A switching system includes a first path of at least one wire connecting a first port to a second port and a second path of at least one wire connecting the first port to a third port, wherein the switching system switches energy transfer between the first path and the second path.

[0215] 179. The interface connector of claim 178, wherein the high voltage energy includes pulsed electric field energy.

[0216] 180. The interface connector according to any one of claims 178-179, wherein the high voltage energy has a voltage of at least 1000 volts.

[0217] 181. The interface connector according to any one of claims 178-180, wherein the high voltage energy has a voltage of at least 2000 volts.

[0218] 182. The interface connector according to any one of claims 178-181, wherein the low voltage energy has a voltage of less than 500 volts.

[0219] 183. The interface connector according to any one of claims 178-182, wherein the low voltage includes voltages in the range of 100 to 200 volts.

[0220] 184. The interface connector according to any one of claims 178-183, wherein the external device includes an electroanalytical mapping system, and wherein the low-voltage energy includes an electrical signal for measuring impedance.

[0221] 185. The interface connector according to any one of claims 178-183, wherein the external device comprises an electroanatomical mapping system, and wherein the low-voltage energy comprises an electrical signal for measuring intracardiac electrical activity.

[0222] 186. The interface connector according to any one of claims 178-185, wherein the switching system performs switching by selectively opening and closing one or more switches.

[0223] 187. The interface connector according to any one of claims 178-186, wherein at least one of the one or more switches can be turned on while at least one of the one or more switches is turned off.

[0224] 188. The interface connector according to any one of claims 178-187, wherein at least one of the one or more switches can be closed while at least one of the one or more switches is open.

[0225] 189. The interface connector according to any one of claims 178-189, wherein the second port electrically connects the generator to two or more of the at least one contact to deliver high-voltage energy therethrough, the interface connector further comprising a passive component network disposed along the first path, wherein the passive component network modulates the energy delivered to the two or more of the at least one contact to prevent conduit failure.

[0226] 190. The interface connector according to any one of claims 178-189, wherein the second port electrically connects the generator to two or more of the at least one contact to deliver high-voltage energy therethrough, the interface connector further comprising a passive component network disposed along the first path, wherein the passive component network increases the current threshold for arc discharge between one or more pairs of conductive wires when the conduit is connected to the two or more of the at least one contact.

[0227] 191. The interface connector according to any one of claims 178-190, further comprising a fourth port for electrically connecting another external device to one or more of the at least one contact, and further comprising a third path of at least one wire connecting the first port and the fourth port.

[0228] 192. The interface connector of claim 191, wherein the other external device comprises a module.

[0229] 193. The interface connector according to any one of claims 178-192, further comprising a fifth port for electrical connection to a return electrode, and a fourth path for connecting at least one wire to the fifth port and the sixth port, the sixth port being configured to connect to the generator.

[0230] 194. A method of treating a patient, comprising:

[0231] The distal end of a catheter is advanced into the patient's heart, wherein the catheter has an energy delivery body positioned along its distal end;

[0232] Position the return electrode at the distal end of the catheter, away from the catheter; position the energy delivery body at a first location along the cardiac tissue region;

[0233] The energy delivery body delivers pulsed electric field energy unipolarly, so that the pulsed electric field energy is directed toward the return electrode through the heart tissue at the first location in order to create a first lesion.

[0234] The energy delivery body is repeatedly repositioned at one or more additional locations along the cardiac tissue region; and

[0235] Pulsed electric field energy is delivered at each of the one or more additional locations to create one or more additional lesions.

[0236] 195. The method of claim 194, wherein the first lesion and the one or more additional lesions are adjacent to each other.

[0237] 196. The method of claim 194, wherein the first lesion and the one or more additional lesions partially overlap each other.

[0238] 197. The method according to any one of claims 194-196, wherein the first lesion and the one or more additional lesions create a closed-shaped continuous lesion around the pulmonary veins of the heart.

[0239] 198. The method of claim 197, wherein delivering the pulsed electric field energy and repeatedly repositioning the energy delivery body creates a series of lesions with a depth sufficient to block conduction between the pulmonary veins and the rest of the heart.

[0240] 199. The method according to any one of claims 194-196, wherein the first lesion and the one or more additional lesions create a continuous lesion having a linear shape.

[0241] 200. The method according to any one of claims 194-196, wherein the cardiac tissue region includes the inner surface of the pulmonary veins.

[0242] 201. The method according to any one of claims 194-200, wherein the one or more additional positions comprise 10-50 additional positions.

[0243] 202. The method according to any one of claims 194-201, wherein the cardiac tissue region includes the superior vena cava, inferior vena cava, atrium, auricle, ventricle, ventricular outflow tract, interventricular septum, ventricular roof, myocardial scar region, myocardial infarction boundary region, myocardial infarction pathway, ventricular endocardium, ventricular epicardium, papillary muscles, or a portion of the Purkinje system.

[0244] 203. The method of any one of claims 194-202, wherein the energy delivery body comprises a cylindrical electrode having a distally facing surface disposed at a tip at the distal end of the catheter, and wherein positioning the energy delivery body comprises positioning the surface against the cardiac tissue.

[0245] 204. The method of claim 203, wherein the surface has a continuous flat surface.

[0246] 205. The method according to any one of claims 203-204, wherein the surface has curved edges.

[0247] 206. The method of any one of claims 194-202, wherein the energy delivery body comprises one or more rings arranged to form a continuous edge, and wherein positioning the energy delivery body comprises positioning the continuous edge against the heart tissue.

[0248] 207. The method of claim 206, wherein the first lesion and the one or more additional lesions each have a hoop shape.

[0249] 208. The method of claim 207, wherein the hoop shape has a diameter of 10-14 mm.

[0250] 209. The method according to any one of claims 194-204, wherein positioning the energy delivery body at the first location and the one or more additional locations is achieved without the use of a guidewire.

[0251] 210. The method according to any one of claims 194-209, further comprising irrigating the cardiac tissue region.

[0252] 211. The method according to any one of claims 194-210, further comprising sensing contact between the energy delivery body and the cardiac tissue region.

[0253] 212. The method according to any one of claims 194-211, further comprising sensing the contact force of the energy delivery body on the cardiac tissue region.

[0254] 213. The method of claim 194, wherein the energy delivery body comprises a single electrode having a surface configured to contact the heart tissue through which the pulsed electric field energy is delivered, wherein the surface has a diameter of approximately 6-8 mm. 2 The surface area, and wherein the pulsed electric field energy is delivered through the surface, generating 2-4 A / mm² during the delivery of the pulsed electric field energy. 2 The current density.

[0255] 214. The method of claim 194, wherein the energy delivery body comprises one or more rings arranged to form a conductive edge, wherein the conductive edge has a diameter of about 8-10 mm. 2 The surface area, and wherein pulsed electric field energy is delivered through the conductive edge, generating 1.5-2 A / mm² during the delivery of the pulsed electric field energy. 2 The current density.

[0256] 215. The method of claim 214, wherein at least one of the one or more rings is individually energized, wherein a portion of the conductive edge energized by the at least one of the one or more rings has a length of about 1.5-2.5 mm. 2 The surface area, and wherein the portion through the conductive edge delivers pulsed electric field energy, generating 6-10 A / mm² when delivering the pulsed electric field energy. 2 The current density.

[0257] 216. A method for treating atrial fibrillation in a patient, comprising:

[0258] The distal end of the catheter is advanced into the patient's heart, wherein the catheter includes a shaft having a longitudinal axis and an energy delivery body having a conductive edge extending around the longitudinal axis;

[0259] The return electrode is positioned at the distal end of the catheter, away from the catheter.

[0260] At least a portion of the conductive edge is positioned against a cardiac tissue region, through which electrical signals associated with atrial fibrillation are transmitted;

[0261] The energy delivery body delivers pulsed electric field energy unipolarly, causing the pulsed electric field energy to be guided toward the return electrode through the heart tissue, thereby creating a lesion that blocks the conduction of the electrical signal.

[0262] 217. The method of claim 216, wherein the conductive edge has an adjustable thickness, further comprising adjusting the thickness of the conductive edge.

[0263] 218. The method of claim 217, wherein adjusting the thickness of the conductive edge comprises pressing the energy delivery body against the heart tissue region.

[0264] 219. The method of claim 218, wherein the energy delivery body has a funnel-shaped shape extending outward from the longitudinal axis of the shaft, wherein the conductive edge extends around the mouth of the funnel-shaped shape, and wherein adjusting the thickness of the conductive edge includes pressing the mouth of the funnel-shaped shape against the cardiac tissue region.

[0265] 220. The method of claim 219, wherein the energy delivery body comprises a plurality of filaments forming the funnel shape, and wherein pressing the mouth portion of the funnel shape against the heart tissue region pulls at least a portion of the plurality of filaments together.

[0266] 221. The method of claim 217, wherein the energy delivery body comprises one or more rings arranged to form the conductive edge, and wherein adjusting the thickness of the conductive edge comprises adjusting the overlap of at least two portions of the one or more rings.

[0267] 222. The method according to any one of claims 216-221, wherein the conductive edge has an adjustable diameter, and further comprises adjusting the diameter of the conductive edge.

[0268] 223. The method of claim 222, wherein adjusting the diameter of the conductive edge comprises pressing the energy delivery body against the heart tissue region.

[0269] 224. The method according to any one of claims 216-223, wherein the energy delivery body comprises at least two individually energized electrodes, and further comprises selecting at least one of the at least two individually energized electrodes to deliver the pulsed electric field energy.

[0270] 225. The method of claim 224, further comprising selecting at least two of the individually energizable electrodes to deliver the pulsed electric field energy in a pattern.

[0271] 226. The method according to any one of claims 216-225, wherein the energy delivery body comprises one or more rings forming the conductive edge, and wherein at least one of the one or more rings is individually energized, wherein a portion of the conductive edge energized by the at least one of the one or more rings has a length of about 3-5 mm. 2 The surface area, and wherein the pulsed electric field energy is delivered through the portion of the conductive edge, generating 3-6 A / mm² when the pulsed electric field energy is delivered. 2 The current density.

[0272] 227. A method for treating a target tissue region of a patient, comprising:

[0273] Position at least one electrode of the catheter in, above or near the target tissue region, wherein the catheter has a baseline energy threshold for internal isolation breakdown.

[0274] Couple the catheter to an energy modulator, wherein the energy modulator is configured to raise the energy threshold for internal isolation breakdown of the catheter above the baseline energy threshold; and

[0275] Energy is delivered at an energy level above the baseline threshold of internal isolation breakdown via the energy modulator and at least one delivery electrode to treat the target tissue region without causing internal isolation breakdown.

[0276] 228. The method of claim 227, wherein the internal isolation breakdown comprises an electric arc discharge.

[0277] 229. The method of any one of claims 227-228, wherein the conduit is configured to deliver radio frequency energy, and the energy includes pulsed electric field energy.

[0278] 230. The method according to any one of claims 227-228, wherein the conduit is configured to deliver microwave energy, and the energy includes pulsed electric field energy.

[0279] 231. The method according to any one of claims 227-230, wherein the conduit is configured to deliver energy generated by an electrical signal having a voltage of up to 1000 volts, and the energy delivered by the energy modulator is generated by an electrical signal having a voltage of at least 2000 volts.

[0280] 232. The method according to any one of claims 227-231, wherein the energy modulator comprises at least one passive component.

[0281] 233. The method of claim 232, wherein the at least one passive component comprises at least one resistor, inductor, capacitor or diode.

[0282] 234. The method of claim 232, wherein the at least one passive component comprises a plurality of resistors.

[0283] 235. The method of claim 232, wherein the at least one passive component comprises at least one resistor, and the method further comprises selecting one or more resistance values ​​of the at least one resistor.

[0284] 236. The method of claim 235, wherein the conduit comprises at least two electrodes each connected to a separate conductor, and further comprises selecting a resistance value that maintains the voltage difference between the separate conductors below a predetermined threshold voltage difference that would cause an arc discharge between the separate conductors.

[0285] 237. The method of claim 236, wherein the predetermined threshold voltage difference is 1500V.

[0286] 238. The method of claim 236, wherein the resistance value causes the total current through the individual conductor to be below a predetermined threshold current level.

[0287] 239. The method of claim 238, wherein the predetermined threshold current level is 40 amperes.

[0288] 240. The method according to any one of claims 232-239, further comprising providing information to the energy modulator for programming the energy modulator to increase the energy threshold for internal isolation breakdown of the catheter above the baseline energy threshold.

[0289] 241. The method of claim 240, wherein providing information includes providing parameters for the energy.

[0290] 242. The method of claim 241, wherein the parameters of the energy include the voltage, frequency, waveform shape, duration, rise pulse time, fall pulse time and / or amplitude of the energy.

[0291] 243. The method of claim 240, wherein providing information includes providing characteristics of the catheter.

[0292] 244. The method of claim 243, wherein the characteristics of the catheter include the number of electrodes, the size of the electrodes, the distance between the electrodes, the brand of the catheter, the model of the catheter, the type of energy the catheter is designed for, or any combination thereof.

[0293] 245. The method of claim 240, wherein providing information includes providing aspects of the environment of the target organizational region.

[0294] 246. The method of claim 232, wherein aspects of the environment include one or more cell types, electrical conductivity, impedance, temperature, and / or blood flow.

[0295] 247. The method according to any one of claims 232-246, wherein treating the target tissue region includes creating at least one lesion to treat atrial fibrillation.

[0296] 248. The method of claim 247, wherein the at least one lesion comprises a plurality of lesions adequately located around the pulmonary vein inlet in the atrium of the patient’s heart, so as to create a conduction block between the pulmonary vein and the atrium.

[0297] 249. The method of claim 247, wherein the at least one lesion comprises a single lesion extending sufficiently around the pulmonary vein inlet in the atrium of the patient's heart to create a conduction block between the pulmonary vein and the atrium.

[0298] 250. A method for processing a target tissue region in the conductive environment of a patient, comprising:

[0299] The distal end of the shaft of a catheter is inserted into the patient, wherein the catheter includes a first lead extending along the shaft to a delivery electrode disposed along the distal end and a second lead extending along the shaft to an additional electrode disposed along the distal end, wherein the catheter is configured such that the first lead and the second lead have a threshold for arc discharge therebetween.

[0300] Position the delivery electrode of the catheter within, above, or near the target tissue region such that the delivery electrode and the additional electrode are exposed to the conductive environment so as to conduct energy through the first and second wires;

[0301] Electrically couple the first and second wires to a common energy source; and

[0302] Pulsed electric field energy is delivered from the common energy source to the target tissue region through at least the first conductor at an energy level exceeding the threshold of arc discharge, while avoiding arc discharge between the first conductor and the second conductor.

[0303] 251. A method for shaping an electric field to create a lesion in a target tissue region, comprising:

[0304] Multiple electrodes of the catheter are positioned in one location such that at least some of the electrodes are able to create the lesion in the target tissue region, wherein the energy delivered by at least some of the electrodes creates the electric field;

[0305] The conduit is coupled to an energy modulator, wherein the energy modulator is programmable to determine the energy provided by at least some of the plurality of electrodes;

[0306] The energy modulator is programmed to generate the desired shape of the electric field; and

[0307] Energy is delivered through the energy modulator and at least one delivery electrode to generate the desired shape of the electric field, thereby creating the lesion in the target tissue region.

[0308] These and other embodiments are described in more detail in the following description in connection with the accompanying drawings.

[0309] Incorporation

[0310] All publications, patents and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication, patent or patent application is specifically and individually cited and incorporated herein by reference. Attached Figure Description

[0311] In the accompanying drawings, which are not necessarily drawn to scale, similar numbers may describe similar components in different views. Similar numbers with different letter suffixes may represent different instances of similar components. The accompanying drawings generally illustrate the various embodiments discussed in this document by way of example rather than limitation.

[0312] Figure 1 The illustration shows how the organizational transformation system can be implemented.

[0313] Figures 2A-2B The illustration shows an embodiment of a treatment catheter configured for delivering local treatment.

[0314] Figure 3 The illustration shows a portion of the heart, including a cross-sectional view of the right and left atria, with a treatment catheter positioned within them.

[0315] Figure 4 The illustration shows how to create a circular treatment zone by repeatedly applying energy point-by-point around the left lower pulmonary vein using a treatment catheter.

[0316] Figure 5 The illustration shows an implementation of the signal waveform defined by the energy delivery algorithm.

[0317] Figure 6 The illustration shows an example waveform defined by the energy delivery algorithm, where the waveform has a voltage imbalance.

[0318] Figure 7 Further examples of waveforms with unequal voltages are illustrated.

[0319] Figure 8 The illustration shows an example of waveforms with unequal pulse widths.

[0320] Figure 9 The illustration shows an example waveform defined by another energy delivery algorithm, where the waveform is single-phase, which is a special case of imbalance where only the positive or negative portion of the waveform exists.

[0321] Figure 10 A further example of a waveform with a single-phase pulse is illustrated.

[0322] Figure 11 An example of a waveform with phase imbalance is illustrated.

[0323] Figure 12 The illustration shows an example waveform defined by another energy delivery algorithm, where the pulse shape is sinusoidal rather than square.

[0324] Figure 13 The illustration shows an implementation method for a conventional ablation catheter.

[0325] Figure 14A The illustration shows the delivery of high-voltage energy through a conventional ablation catheter with multiple electrodes.

[0326] Figure 14B The diagram shows... Figure 14A The cross-section of the shaft is shown in the figure, with the insulated wire corresponding to the electrode.

[0327] Figure 15 A resistor is schematically illustrated, positioned to guide energy through a wire in a predetermined manner, such that the voltage difference is kept below a specific threshold level.

[0328] Figures 16A-16B The illustration shows the increase in the arc discharge threshold when using a resistor network as described in this article.

[0329] Figures 17A-17CThe illustration shows how to shape an electric field delivered by a conduit using the resistor network and system described herein.

[0330] Figure 18 A schematic diagram of a cross-section of the lumen of a pulmonary vein surrounded by heart tissue is provided, along with electrodes illustrated to contact the heart tissue via the lumen.

[0331] Figure 19 The diagram is based on Figure 18 The graph shows the relationship between energy and the depth of the processing region when the method shown delivers energy.

[0332] Figures 20-21 The current distribution of PEF energy emitted from the delivery electrode of the catheter under different conditions was illustrated through mathematical modeling.

[0333] Figure 22 A graphical illustration of current density versus penetration depth is provided in homogeneous and heterogeneous structures.

[0334] Figures 23A-23B The figure illustrates the effect of contact force on the size of the lesion, particularly its width and depth.

[0335] Figure 24 The thermal profile of the conduit electrode is shown in the figure.

[0336] Figure 25 The illustration shows a treatment conduit with heat sensing and irrigation capabilities.

[0337] Figure 26 The illustration shows an example setup in which an interface connector is used in conjunction with an implementation of an organizational transformation system.

[0338] Figures 27-28 The illustration shows an implementation of the interface connector.

[0339] Figure 29 The diagram illustrates the result of an AND operation between the generator foot switch signal and the R-wave trigger signal from the heart monitor.

[0340] Figure 30 The illustration shows an implementation of a connector suitable for use when the signal between the conduit and the EP signal amplifier has a different frequency than the PEF output.

[0341] Figure 31 The illustration shows an implementation of the interface connector.

[0342] Figure 32 An implementation of an interface connector with a component network is illustrated.

[0343] Figure 33 Another implementation of an interface connector with a component network is illustrated.

[0344] Figure 34 The illustration shows an implementation of a tissue modification system for patients.

[0345] Figure 35 The illustration shows an implementation of a tissue modification system for a patient, wherein the treatment catheter includes a specific conventional catheter.

[0346] Figure 36 The illustration shows an embodiment of a treatment catheter configured to deliver "single-dose" treatment.

[0347] Figures 37A-37B An embodiment of a delivery electrode configured to deliver a “single-dose” treatment is illustrated, wherein the delivery electrode has a cup-shaped or funnel-shaped form.

[0348] Figures 38A-38B The diagram shows that Figures 37A-37B The delivery electrode is applied to the surface.

[0349] Figure 39 The diagram shows... Figures 38A-38B One implementation of the delivery electrode in the example is in which a portion of a plurality of wires is covered with an insulating material.

[0350] Figure 40A A schematic diagram of a cross-section of the lumen of a pulmonary vein surrounded by cardiac tissue is provided, and the diagram shows a treatment catheter having delivery electrodes that contact the cardiac tissue at various locations via the lumen.

[0351] Figure 40B The diagram is based on Figure 40A The graph shows the correlation between energy and the depth of the processing region when the method shown delivers energy.

[0352] Figure 41 An embodiment of a delivery electrode including an initial single ring forming a double-layered edge is illustrated.

[0353] Figure 42 Provided Figure 41 The side view of the delivery electrode depicted in the figure.

[0354] Figures 43A-43E The diagram shows... Figures 41-42 Deployment of delivery electrodes.

[0355] Figure 44A The illustration shows an embodiment of a delivery electrode with two rings that extend at least partially around an edge, such that the circular edge consists of two layers of wires in two portions.

[0356] Figure 44B The diagram illustrates the separation for visualization purposes. Figure 44A The two rings.

[0357] Figure 45 A side view of the delivery electrode depicted in Figure 44 is provided.

[0358] Figure 46A The illustration shows an embodiment of a delivery electrode with three rings that extend at least partially around an edge, such that the circular edge consists of two layers of wires in three sections.

[0359] Figure 46B The diagram illustrates the separation for visualization purposes. Figure 16A The three rings.

[0360] Figure 47 Provided Figure 46A The side view of the delivery electrode depicted in the figure. Detailed Implementation

[0361] Devices, systems, and methods are provided for treating cardiac conditions—particularly for treating the occurrence of arrhythmias, and more particularly for treating atrial fibrillation, atrial flutter, ventricular tachycardia, Wolff-Parkinson-White syndrome, and / or atrioventricular nodal reentrant tachycardia. These devices, systems, and methods deliver therapeutic energy to portions of the heart to provide tissue modification, such as delivering therapeutic energy to the entrance of the pulmonary veins in the treatment of atrial fibrillation. Targeted anatomical locations include the superior vena cava, inferior vena cava, right pulmonary vein, left pulmonary vein, right atrium, right atrial appendage, left atrium, left atrial appendage, right ventricle, left ventricle, right ventricular outflow tract, left ventricular outflow tract, interventricular septum, left ventricular roof, myocardial scar region, myocardial infarction boundary region, myocardial infarction pathway, ventricular endocardium, ventricular epicardium, papillary muscles, and Purkinje system, etc. Treatment is delivered at isolated sites or in a series of interconnected treatments. Treatment types include creating left atrial roof lines, left atrial posterior / inferior lines, posterior wall isolation, lateral mitral isthmus lines, septal mitral isthmus lines, left atrial appendage, right tricuspid isthmus (CTI), pulmonary vein isolation, superior vena cava isolation, Marshall vein, lesion creation using complex fragmented atrial electrocardiography (CFAE), lesion creation using localized pulse and rotor modulation (FIRM), and targeted ganglion ablation. Such tissue modification creates conduction blocks within the tissue to prevent the transmission of aberrant electrical signals. The equipment, systems, and methods are typically used in electrophysiology laboratories or controlled operating rooms equipped with fluoroscopy and advanced ECG recording and monitoring capabilities. The electrophysiologist (EP) is the intended primary user of the system. The EP will be assisted and supported by trained nurses, technicians, and, if possible, other electrophysiologists. Generally, the tissue modification system includes a dedicated catheter, a high-voltage waveform generator, and at least one different energy delivery algorithm. Additional accessories and equipment may be used. Example implementations of the dedicated catheter design are provided herein and include various delivery types, including local delivery, "single-drop" delivery, and various possible combinations. For illustrative purposes, a simplified design is provided when describing the overall system. This simplified design provides unipolar local therapy. However, it will be understood that many other implementations are also provided.

[0362] Figure 1 An embodiment of the tissue modification system 100 is illustrated, comprising a processing catheter 102, a mapping catheter 104, a return electrode 106, a waveform generator 108, and an external cardiac monitor 110. In this embodiment, the heart is accessed via the right femoral vein FV using a suitable access procedure such as the Seldinger technique. Typically, a sheath 112 is inserted into the femoral vein FV, which acts as a conduit through which various catheters and / or tools, including the processing catheter 102 and the mapping catheter 104, can be advanced. It will be understood that in some embodiments, the processing catheter 102 and the mapping catheter 104 are combined into a single device. Figure 1 As shown, the distal ends of catheters 102 and 104 are advanced through the inferior vena cava, through the right atrium, through transseptal puncture, and into the left atrium to access the pulmonary veins. Mapping catheter 104 is used to perform cardiac mapping, which is the process of identifying the temporal and spatial distribution of myocardial potentials during a specific cardiac rhythm. Cardiac mapping during abnormal rhythms aims to elucidate the mechanisms of the rhythm, describe the propagation of activation within the region of interest from its initiation to its completion, and identify the initiation or critical sites of conduction as targets for treatment. Once the desired treatment location is identified, treatment energy is delivered using treatment catheter 102.

[0363] In this embodiment, the proximal end of the processing catheter 102 is electrically connected to a waveform generator 108, wherein the generator 108 is software-controlled and has a modulated energy output that creates high-frequency, short-duration energy delivered to the catheter 102. It will be understood that in various embodiments, the output is controlled or modified to achieve a desired voltage, current, or combination thereof. In this embodiment, the proximal end of the mapping catheter 104 is also electrically connected to the waveform generator 108, and the generator 108 includes electronics for performing mapping procedures. However, it will be understood that the mapping catheter 104 may alternatively be connected to a separate external device with the capability to provide mapping procedures, such as an electroanatomical mapping (EAM) system (e.g., Biosense Webster / Johnson & Johnson). System, St. Jude Medical / Abbott's EnSite TM Systems, Philips' KODEX-EPD system, Boston Scientific's Rhythmia HDX TM (System). Similarly, in some implementations, instead of using a separate mapping catheter 104, mapping features are incorporated into catheter 102.

[0364] In this embodiment, generator 108 is connected to an external cardiac monitor 110 to allow energy delivery coordinated with cardiac signals sensed from patient P. The generator synchronizes its energy output with the patient's heart rhythm. The cardiac monitor provides a trigger signal to generator 108 when it detects an R wave in the patient's cardiac cycle. This trigger signal and the generator's algorithm reliably synchronize energy delivery with the patient's cardiac cycle to reduce the likelihood of arrhythmias due to energy delivery. Typically, a foot switch allows the user to initiate and control the delivery of energy output. The generator user interface (UI) provides the user with audio and video information about energy delivery and the generator's operational status.

[0365] In this embodiment, the treatment catheter 102 is designed to be monopolar, wherein the distal end of the catheter 108 has a delivery electrode 122 and a return electrode 106 is positioned on the skin outside the body, typically on the thigh, lower back, or back. Figure 2A An embodiment of a treatment catheter 102 configured to deliver local treatment is illustrated. In this embodiment, the catheter 102 includes an elongated shaft 120 having a delivery electrode 122 located near its distal end 124 and a handle 126 located near its proximal end 128. The delivery electrode 122 is shown as a "solid tip" electrode with a cylindrical shape and a distal side having a continuous surface. In some embodiments, the cylindrical shape has a diameter of about 2-3 mm across its distal side and a length of about 1 mm, 2 mm, 1-2 mm, 3 mm, 4 mm, 3-4 mm, 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, etc., along the shaft 120. It is understood that such an electrode is typically hollow, but is referred to as solid due to its visual appearance. In some embodiments, the catheter 102 has a total length of 50-150 cm, preferably 100-125 cm, more preferably 110-115 cm. Similarly, in some embodiments, it has an outer diameter of 3-15 Fr, preferably 4-12 Fr, and more preferably 7-8.5 Fr, of 7 Fr. It is understood that in some embodiments, the shaft 120 has a deflectable end 121, and optionally, the deflectable end 121 may have a length of 50-105 mm, thereby producing a curve with a diameter ranging from about 15 to 55 mm. Deflection can be achieved by various mechanisms, including a pull wire extending to the handle 126. Thus, the handle 126 is used to manipulate the catheter 102, particularly guiding the distal end 124 during delivery and treatment. Energy is provided to the catheter 102 via a cable 130 connectable to the generator 108, and thus to the delivery electrode 122.

[0366] A pulsed electric field (PEF) is provided by generator 108 and delivered to the tissue via delivery electrode 122 placed on or near the target tissue region. It is understood that in some embodiments, delivery electrode 122 is positioned in contact with a conductive material that also contacts the target tissue. Such a solution may include isotonic or hypertonic solutions. These solutions may also include adjuvant materials, such as chemotherapy or calcium, to further enhance the treatment effect on localized areas and potential infiltration areas of the target tissue type. High-voltage, short-duration biphasic electrical pulses are then delivered via electrode 122 near the target tissue. These electrical pulses are provided by at least one energy delivery algorithm 152. In some embodiments, each energy delivery algorithm 152 specifies a signal having a waveform comprising a series of energy packets, where each energy packet comprises a series of high-voltage pulses. In such embodiments, algorithm 152 specifies parameters of the signal, such as energy amplitude (e.g., voltage) and duration of energy application, which consist of the number of packets, the number of pulses within a packet, and the fundamental frequency of the pulse sequence, etc. Additional parameters may include the switching time between polarities in the biphasic pulse, the silence time between biphasic cycles, and the rest time between wave packets, which will be described in more detail later. There may be a fixed rest period between wave packets, or the wave packets may be gated according to the cardiac cycle and thus vary with the patient's heart rate. There may be intentionally varying rest period algorithms, or no rest period may be applied between wave packets. Feedback loops based on sensor information and automatic shutdown specifications and / or the like may be included.

[0367] It is understood that, in various embodiments, the catheter 102 includes a variety of specialized features. For example, in some embodiments, the catheter 102 includes a mechanism for measuring the contact force applied by the catheter tip to the patient's heart wall in real time during the procedure. In some embodiments, this mechanism is included within the shaft 120 and includes a triaxial optical force sensor utilizing white light interferometry. By monitoring and modifying the applied force throughout the procedure, the user is able to better control the catheter 102 to create a more consistent and effective lesion.

[0368] In some implementations, such as Figure 2B As shown, catheter 102 includes one or more additional electrodes 125 (e.g., loop electrodes) positioned along shaft 120 near delivery electrode 122. In some embodiments, some or all of the additional electrodes may be used for stimulation and recording (for electrophysiological mapping), so a separate cardiac mapping catheter is not required when catheter 102 is used to create lesions or for other purposes such as sensing.

[0369] In some embodiments, the catheter 102 includes a thermocouple temperature sensor, optionally embedded in the delivery electrode 122. Similarly, in some embodiments, the catheter 102 includes a lumen that can be used for irrigation and / or aspiration. Typically, the lumen is connected to one or more ports along the distal end of the catheter 102, such as for injecting isotonic saline solution for irrigation or, for example, for removing microbubbles.

[0370] In some embodiments, catheter 102 includes one or more sensors that can be used to determine temperature, impedance, resistance, capacitance, conductivity, dielectric constant, and / or conductivity coefficient, etc. In some embodiments, one or more electrodes among the electrodes act as one or more sensors. In other embodiments, one or more sensors are separate from the electrodes. Sensor data can be used to plan treatment, monitor treatment, and / or provide direct feedback via processor 154, which in turn can modify energy delivery algorithm 152. For example, impedance measurements can be used not only to determine the initial dose to be applied but also to determine whether further treatment is needed.

[0371] Return to reference Figure 1 In this embodiment, generator 108 includes a user interface 150, one or more energy delivery algorithms 152, a processor 154, a data storage / retrieval unit 156 (such as a memory and / or database), and an energy storage subsystem 158 for generating and storing the energy to be delivered. In some embodiments, one or more capacitors are used to store / deliver energy; however, any other suitable energy storage element may be used. Additionally, one or more communication ports are included.

[0372] In some embodiments, generator 108 includes three subsystems: 1) a high-energy storage system, 2) a high-voltage, intermediate-frequency switching amplifier, and 3) a system controller, firmware, and user interface. In this embodiment, the system controller includes a cardiac synchronization trigger monitor that allows the pulse energy output to be synchronized with the patient's heart rhythm. The generator uses an alternating current (AC) power supply to power multiple direct current (DC) power supplies. The generator's controller can charge the high-energy capacitor storage group with the DC power supply before initiating energy delivery. Upon initiation of therapeutic energy delivery, the generator's controller, high-energy storage group, and biphasic pulse amplifier can operate simultaneously to create a high-voltage, intermediate-frequency output.

[0373] It should be understood that various generator electrical architectures can be employed to execute energy delivery algorithms. In particular, in some implementations, advanced switching systems are used, which are capable of directing the pulsed electric field circuitry to energy delivery electrodes separate from the same energy storage and high-voltage delivery system. Furthermore, generators used in advanced energy delivery algorithms employing rapidly changing pulse parameters (e.g., voltage, frequency, etc.) or multiple energy delivery electrodes can utilize modular energy storage and / or high-voltage systems, thereby facilitating highly customizable waveform and regional pulse delivery paradigms. It should also be understood that the electrical architectures described above are merely illustrative, and systems delivering pulsed electric fields may or may not include additional switching amplifier components.

[0374] User interface 150 may include a touchscreen and / or more conventional buttons to allow the operator to input patient data, select a processing algorithm (e.g., energy delivery algorithm 152), initiate energy delivery, view records stored on storage / retrieval unit 156, and / or otherwise communicate with generator 108.

[0375] In some implementations, the user interface 150 is configured to receive operator-defined input. Operator-defined input may include the duration of energy delivery, one or more other timing aspects of the energy delivery pulse, power and / or operating mode, or combinations thereof. Example operating modes may include (but are not limited to): system startup and self-test, operator input, algorithm selection, pre-processing system status and feedback, energy delivery, post-energy delivery display or feedback, processing data review and / or download, software update, or any combination or sub-combination thereof.

[0376] As described above, in some embodiments, system 100 also includes a mechanism for acquiring an electrocardiogram (ECG) when cardiac synchronization is required, such as an external cardiac monitor 110. Example cardiac monitors are available from AccuSync Medical Research Corporation and Ivy Biomedical Systems, Inc. In some embodiments, the external cardiac monitor 110 is operatively connected to generator 108. The cardiac monitor 110 can be used to continuously acquire ECG signals. An external electrode 172 can be applied to patient P to acquire the ECG. Generator 108 analyzes one or more cardiac cycles and identifies the start of a time period in which energy can be safely applied to patient P, thereby providing the ability to synchronize energy delivery with the cardiac cycle. In some embodiments, this time period is within milliseconds of the R wave (of the ECG QRS complex) to avoid inducing arrhythmias—which could occur if the energy pulse is delivered on the T wave. It should be understood that such cardiac synchronization is typically employed when using unipolar energy delivery; however, it can also be employed as part of other energy delivery methods.

[0377] In some embodiments, among other activities, processor 154 modifies and / or switches between energy delivery algorithms, monitors energy delivery and any sensor data, and reacts to the monitored data via a feedback loop. In some embodiments, processor 154 is configured to execute one or more algorithms to operate a feedback control loop based on one or more measured system parameters (e.g., current), one or more measured organizational parameters (e.g., impedance), and / or combinations thereof.

[0378] Data storage / retrieval unit 156 stores data, such as data relating to the delivered processing, and can optionally be downloaded by connecting a device (e.g., a laptop computer or thumb drive) to the communication port. In some embodiments, the device has local software for directing information downloads, such as instructions stored on data storage / retrieval unit 156 and executable by processor 154. In some embodiments, user interface 150 allows an operator to select data to be downloaded to a device and / or system, such as, but not limited to, computer devices, tablets, mobile devices, servers, workstations, cloud computing devices / systems, etc. The communication port, which allows wired and / or wireless connectivity, can allow data downloads as described above, but can also allow data uploads, such as uploading custom algorithms or providing software updates.

[0379] As described herein, the various energy delivery algorithms 152 are programmable or can be pre-programmed into the generator 108, such as by storing them in memory or the data storage / retrieval unit 156. Alternatively, the energy delivery algorithms can be added to the data storage / retrieval unit for execution by the processor 154. Each of these algorithms 152 can be executed by the processor 154.

[0380] It is understood that, in some implementations, system 100 includes an automated processing delivery algorithm that dynamically responds to and adjusts and / or terminates processing in response to inputs such as temperature, impedance at various voltages or AC frequencies, processing duration or other timing aspects of the energy delivery pulse, processing power and / or system state.

[0381] As previously described, in some embodiments, the cardiac monitor provides a trigger signal to generator 108 when it detects an R wave in the patient's cardiac cycle. This trigger signal and the generator's algorithm reliably synchronize energy delivery with the patient's cardiac cycle to reduce the likelihood of arrhythmias due to energy delivery. This trigger occurs within milliseconds of the R wave peak (of the ECG QRS complex) to avoid inducing arrhythmias (which could occur if the energy pulse were delivered on the T wave) and also ensures that energy delivery occurs during a consistent phase of cardiac contraction. It should be understood that such cardiac synchronization is typically employed when using unipolar energy delivery; however, it can also be employed as part of other energy delivery methods.

[0382] In this embodiment, generator 108 is connected to an external cardiac monitor 110 to allow energy to be delivered in coordination with cardiac signals sensed from patient P.

[0383] In some implementations, generator 180 receives feedback from cardiac monitor 110 and responds based on the received information. In some implementations, generator 180 receives information about the patient's heart rate and, for example, stops or modifies energy delivery by selecting a different energy delivery algorithm 152. In some implementations, generator 180 stops energy delivery when the heart rate reaches or drops below a threshold, such as 30 bpm or 20 bpm. Optionally, when the heart rate reaches or drops below a lower threshold, the generator can provide an indication, such as a visual or auditory indication, for example, a flashing yellow light when the heart rate reaches 30 bpm and a solid red light when the heart rate reaches 20 bpm. Given that sporadic low heart rates may indicate erroneous readings, such safety measures ensure that processing energy is not delivered at inappropriate times.

[0384] In some implementations, generator 108 modifies energy delivery based on information from cardiac monitor 110. For example, in some implementations, energy delivery is provided at a 1:1 ratio when the heart rate is within a predetermined range, such as 40 bpm to 120 bpm. This involves delivering PEF energy at appropriate intervals between each heartbeat. In some implementations, if the heart rate exceeds this range, for example, if the heart rate exceeds 120 bpm, generator 108 modifies energy delivery. In some implementations, the energy delivery is modified to a 2:1 ratio (two heartbeats: one delivery), where PEF energy is delivered at appropriate intervals every other heartbeat. It is understood that various ratios in the form of m:n (where m and n are integers) can be used, such as 3:1, 3:2, 4:1, 4:3, 5:1, etc. It is also understood that in some implementations, the heart rate can be paced to achieve a desired heart rate. Such pacing can be provided by a separate or integrated pacemaker. In some implementations, such pacing is provided by a catheter positioned in the coronary sinus, which is used for recording during surgery but can also be used for pacing. Such pacing can be triggered by generator 108 or cardiac monitor 110.

[0385] In some embodiments, generator 108 stops or modifies energy delivery based on information from other sources, such as various sensors, including temperature sensors, impedance sensors, contact or contact force sensors, etc. In some embodiments, generator 108 modifies energy delivery based on sensed temperature (e.g., on catheter 102, in nearby tissue, in nearby structures, etc.). In some embodiments, energy delivery is modified to a 2:1 ratio, wherein PEF energy is delivered at appropriate intervals equal to one heartbeat when a predetermined threshold is reached. Such modification reduces any small thermal effects, thereby lowering the sensed temperature. It will be understood that various ratios, such as 3:1, 3:2, 4:3, 4:1, 5:1, etc., can be used.

[0386] As previously described, one or more energy delivery algorithms 152 are programmable or can be pre-programmed into generator 108 for delivery to patient P. One or more energy delivery algorithms 152 specify an electrical signal that provides energy to be delivered to cardiac tissue, said energy being non-thermal (e.g., below the threshold for thermal ablation; below the threshold for inducing coagulation thermal injury), thereby reducing or avoiding inflammation and / or preventing denaturation of matrix proteins in the luminal structures. It is understood that the non-thermal energy is also not cryogenic (i.e., it is above the threshold for thermal injury caused by freezing). Therefore, the temperature of the target tissue is maintained within a range between baseline body temperature (such as 35°C–37°C, but can be as low as 30°C) and the thermal ablation threshold. Therefore, target ranges for tissue temperature include 30–65°C, 30–60°C, 30–55°C, 30–50°C, 30–45°C, and 30–35°C. Therefore, the lesion in the cardiac tissue is not created by thermal injury because the tissue temperature is maintained below the thermal ablation threshold (e.g., 65°C). Furthermore, the impedance of the tissue typically remains below the threshold generated by thermal ablation. Carbonization and thermal damage to the tissue alter the conductivity of cardiac tissue. Such an increase in impedance / decrease in conductivity often indicates thermal damage and reduces the tissue's ability to receive further energy. In some cases, the impedance of the system circuitry from cathode to anode remains in the range of 25-250 Ω or 50-200 Ω during PEF energy delivery. Generally, Algorithm 152 is tailored to influence tissue to a predetermined depth and / or volume and / or for a specific type of cellular response to the delivered energy. However, it is understood that the pulsed electric field energy described herein can be used more freely without negative effects compared to other types of energy, such as those that cause thermal damage. For example, since the energy does not cause thermal damage, the tissue can be overtreated to ensure sufficient lesion formation. For example, in a 2 mm thick tissue layer, sufficient energy to create a lesion 6 mm deep can be applied to ensure transmural damage. Typically, the additional energy dissipates from nearby critical structures through the transverse tissue plane. Specifically, the pericardial fluid surrounding the heart dissipates energy, thus protecting extracardiac structures such as the esophagus, phrenic nerve, coronary arteries, lungs, and bronchioles from damage. This is not the case when energy is delivered to create a lesion through thermal injury. In those cases, the propagation of conductive heat energy outside the target myocardial tissue can lead to thermal injury to non-target extracardiac structures. Excessive thermal injury to the esophagus can lead to esophageal ulcers, which can worsen into life-threatening atrial-esophageal fistulas. Thermal injury to the phrenic nerve can lead to permanent diaphragmatic paralysis, causing permanent shortness of breath and fatigue. Thermal injury to the coronary arteries can lead to coronary artery spasm, potentially causing temporary or even permanent chest pressure / pain. Furthermore, thermal injury in the region of the heart located in the pulmonary veins can lead to pulmonary vein stenosis. Pulmonary vein stenosis is a known complication of radiofrequency ablation near the pulmonary veins in patients with atrial fibrillation.This pathological process is associated with thermal damage to tissues that leads to postoperative fibrosis and scarring. Stenosis has been described in patients treated with various forms of thermal energy, including radiofrequency energy and cryoablation.

[0387] Because the PEF lesions described in this paper are not created by thermal injury, the false positive confirmation rate of electrical conduction blockade is also reduced. Thermal injury can lead to acute myocardial edema (i.e., fluid buildup and swelling). When testing the conductivity across the thermally ablated tissue area, the tissue may exhibit blocked conduction; however, such blockade may only be a result of temporary edema. After a period of recovery to allow the swelling to subside, the treated tissue area will no longer be transmural and nonconductive. Furthermore, acute edema caused by thermal injury reduces the ability to reprocess the tissue area. Once a tissue area has undergone a certain degree of thermal injury, the resulting edema alters the tissue's electrical and thermal conductivity properties. Therefore, it is difficult to obtain results similar to the initial response in the tissue. Consequently, any attempt at reprocessing is less effective in both acute and chronic cases. These problems are avoided by the energy delivery described in this paper.

[0388] Figure 3 The diagram illustrates a portion of the heart (H), showing a perspective view of the right atrium (RA) and left atrium (LA) during the management of atrial fibrillation. The largest pulmonary veins are the four main pulmonary veins (right superior pulmonary vein RSPV, right inferior pulmonary vein RIPV, left superior pulmonary vein LSPV, and left inferior pulmonary vein LIPV), with two draining from each lung into the left atrium (LA) of the heart (H). Each pulmonary vein connects to the capillary network in the alveoli of each lung and delivers oxygenated blood to the left atrium (LA). Left atrial muscle tissue extends from the left atrium (LA) and surrounds the proximal pulmonary veins. Superior veins with longer muscle sleeves have been reported to be more likely to induce arrhythmias than inferior veins. Generally, the length of pulmonary vein muscle sleeves varies between 13 mm and 25 mm. Pulmonary vein morphology has been reported to influence the occurrence of arrhythmias. Similarly, cellular electrophysiology and other aspects of pulmonary veins are associated with the occurrence and propagation of arrhythmias.

[0389] Several methods are used to determine which tissues to target for treatment, such as anatomical indications and cardiac mapping. Typically, a mapping catheter is selected to anastomose the pulmonary veins as desired, adapting to their size and anatomical form. The mapping catheter allows for the recording of electrograms from the pulmonary vein ostium and deep within the pulmonary vein; these electrograms are displayed and timed for the user. The treatment catheter 102 is initially placed deep within the pulmonary vein and gradually withdrawn near the opening of the mapping catheter. Mapping and treatment then commence.

[0390] Current understanding of pulmonary vein electrophysiology is that most fibers in the pulmonary veins are round and do not carry conduction into the vein. The electrical conduction pathway is a longitudinal fiber extending between the left atrial (LA) and the pulmonary vein. Pulmonary vein isolation is achieved by ablating these connecting longitudinal fibers. For the left pulmonary vein, pacing of the distal coronary sinus tends to increase the separation of atrial signals and pulmonary vein potentials, making them more electrically visible. Signals from within the pulmonary veins are evaluated. Each individual signal contains a far-field atrial signal (generally low amplitude) and a sharp, localized pulmonary vein spike. The earliest pulmonary vein spike represents the junction between the pulmonary vein and the atrium. If examining pulmonary vein spikes and atrial potentials, these electrograms are widely spaced at some poles of the mapping catheter, while at other sites there is a fusion potential of atrial and pulmonary vein (PV) signals. The latter indicates the location of the longitudinal fibers and potential treatment sites.

[0391] In some implementations, such as Figure 3 As shown, a circular treatment zone is created around the left inferior pulmonary vein LIPV using treatment catheter 102 (with mapping assistance) to treat the tissue around the opening of the left inferior pulmonary vein LIPV in a point-by-point manner. In some cases, specialized navigation software can be used to allow proper positioning of treatment catheter 120. Delivery electrode 122 is positioned close to or against the target tissue area and energy is supplied to delivery electrode 122 to create treatment zone A. Because energy is delivered to a local area (local delivery), electrical energy is concentrated on a smaller surface area, resulting in a stronger effect than delivery via electrodes extending circumferentially around the lumen or opening. This also forces electrical energy to be delivered in a staged regional approach, thereby mitigating the potential effects of preferential current pathways through surrounding tissue. These preferential current pathways are areas with electrical properties that cause a local increase in current flowing through them rather than through adjacent areas. Such pathways can lead to an irregular current distribution around the perimeter of the target lumen and may thus distort the electric field, resulting in irregular increases in treatment effect in some areas and decreases in treatment effect in others. This can be mitigated or avoided by using local treatment that stabilizes the treatment effect around the perimeter of the target area. Therefore, by supplying energy to a specific area at a time, electrical energy is "forced" to cross different areas of the perimeter, thereby ensuring an increased degree of circumferential regularity in processing. Figure 4The illustration illustrates the creation of circular treatment zones by repeatedly applying energy point-by-point around the left lower pulmonary vein (LIPV) using a treatment catheter 102. As shown, in this embodiment, each treatment zone A overlaps with adjacent treatment zones A to create a continuous treatment area. The size and depth of each treatment zone A may depend on various factors, such as parameter values, treatment time, tissue characteristics, etc. It is understood that the number of treatment zones A may vary depending on various factors, particularly the unique anatomical and electrophysiological conditions of each patient. In some embodiments, the number of treatment zones A includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, or more.

[0392] When all electrical connections between the atria and veins have been processed, electrical silence exists within the pulmonary veins, with only far-field atrial signals recorded. Occasionally, spikes in electrical activity may be observed within the pulmonary veins, but these do not conduct to the rest of the atria; these clearly indicate an electrical interruption between the veins and the rest of the atrial myocardium.

[0393] Depending on the clinical presentation, additional treatment areas may be created in other locations to treat arrhythmias in the right or left atrium. Testing is then performed to ensure that each target pulmonary vein is effectively isolated from the main body of the left atrium.

[0394] Energy delivery algorithm

[0395] It is understood that various energy delivery algorithms 152 can be used. In some implementations, algorithm 152 specifies a signal having a waveform comprising a series of energy packets, each energy packet comprising a series of high-voltage pulses. In such implementations, algorithm 152 specifies parameters of the signal, such as energy amplitude (e.g., voltage) and duration of energy application—which consists of the number of packets, the number of pulses within a packet, and the fundamental frequency of the pulse sequence. Additional parameters may include the switching time between polarities in biphasic pulses, the silence time between biphasic periods, and the rest time between packets, which will be described in more detail later. There may be a fixed rest period between packets, or the packets may be gated according to the cardiac cycle and thus vary with the patient's heart rate. There may be algorithms for intentionally varying the rest period, or no rest period may be applied between packets. Feedback loops based on sensor information and automatic shut-off specifications and / or the like may be included.

[0396] Figure 5The illustration shows an embodiment of the waveform 400 of the signal defined by the energy delivery algorithm 152. Two wave packets are shown—a first wave packet 402 and a second wave packet 404—separated by a pause period 406. In this embodiment, each wave packet 402, 404 consists of a first biphase cycle (including a first positive pulse peak 408 and a first negative pulse peak 410) and a second biphase cycle (including a second positive pulse peak 408' and a second negative pulse peak 410'). The first and second biphase pulses are separated by a quiet time 412 (i.e., a pause) between each biphase cycle. In this embodiment, the biphase pulses are symmetrical, so the set voltage 416 is the same for both positive and negative peak values. Here, the biphase symmetrical wave is also a square wave, such that the amplitude and duration of the positive voltage wave are approximately equal to the amplitude and duration of the negative voltage wave.

[0397] A. Voltage

[0398] The voltage used and considered can be the top of a square wave, a peak in a sine or sawtooth waveform, or the RMS voltage of a sine or sawtooth waveform. In some implementations, energy is delivered in a unipolar manner, and each high-voltage pulse or set voltage 416 is between about 500V and 10,000V, particularly about 1000V-2000V, 2000V-3000V, 3000V-3500V, 3500V-4000V, 3500V-5000V, 3500V-6000V, including all values ​​and sub-ranges in between, including about 1000V, 2000V, 2500V, 2800V, 3000V, 3300V, 3500V, 3700V, 4000V, 4500V, 5000V, 5500V, 6000V, etc.

[0399] It is understood that the set voltage 416 may vary depending on whether the energy is delivered in a monopolar or bipolar manner. In bipolar delivery, a lower voltage can be used due to the smaller, more directional electric field. The choice of bipolar voltage for treatment depends on the spacing between the electrodes, while a monopolar electrode configuration using one or more distally distributed pad electrodes can deliver the energy with less consideration for the precise placement of the catheter electrodes and the distributed electrodes on the body. In monopolar electrode implementations, due to the dispersed behavior of the delivered energy through the body to the distributed electrodes, the effective spacing distance is approximately 10 cm to 100 cm, thus a larger voltage is typically used. Conversely, in bipolar electrode configurations, the relatively close active areas of the electrodes, ranging from 0.5 mm to 10 cm, including 1 mm to 1 cm, have a greater impact on the concentration of electrical energy delivered to the tissue and the effective dose from the spacing distance. For example, if the target voltage-to-distance ratio is 3000 V / cm to induce the desired clinical effect at an appropriate tissue depth (1.3 mm), changing the spacing distance from 1 mm to 1.2 mm would result in a necessary increase in the treatment voltage from 300 V to approximately 360 V, a change of 20%.

[0400] B. Frequency

[0401] It is understood that the number of biphasic cycles per second is the frequency of the signal when it is continuous. In some implementations, biphasic pulses are used to reduce unwanted muscle stimulation, particularly myocardial stimulation. In other implementations, the pulse waveform is monophasic and does not have a defined inherent frequency. Instead, the fundamental frequency can be considered by doubling the length of the monophasic pulse to derive the frequency. In some implementations, the signal has a frequency in the range of 50 kHz to 1 MHz, more specifically in the range of 50 kHz to 1000 kHz. It is understood that at some voltages, frequencies at or below 100-250 kHz may cause unwanted muscle stimulation. Therefore, in some implementations, the signal has a frequency in the range of 300-800 kHz, 400-800 kHz, or 500-800 kHz, such as 300 kHz, 400 kHz, 450 kHz, 500 kHz, 550 kHz, 600 kHz, 650 kHz, 700 kHz, 750 kHz, and 800 kHz. Furthermore, cardiac synchronization is often used to reduce or avoid unwanted myocardial stimulation during sensitive rhythms. It is understandable that higher frequencies can be used even with components that minimize signal artifacts.

[0402] C. Voltage-frequency balance

[0403] The frequency of the delivered waveform can be varied synchronously with respect to the processing voltage to maintain sufficient processing effectiveness. Such coordinated variations will include a frequency reduction that causes a stronger effect combined with a voltage reduction that causes a weaker effect. For example, in some cases, a waveform frequency of 3000V and 600kHz can be used to deliver processing in a unipolar manner, while in other cases, a waveform frequency of 2000V and 400kHz can be used.

[0404] D. Wave packet

[0405] As previously stated, Algorithm 152 typically specifies a signal having a waveform comprising a series of energy packets, where each energy packet comprises a series of high-voltage pulses. The cycle count 420 is half the number of pulses within each biphase packet. (Reference) Figure 5 The cycle count 420 of the first packet 402 is 2 (i.e., four biphase pulses). In some embodiments, the cycle count 420 is set between 2 and 1000 per packet, including all values ​​and sub-ranges therebetween. In some embodiments, the cycle count 420 is 5-1000 per packet, 2-10 per packet, 2-20 per packet, 2-25 per packet, 10-20 per packet, 20 per packet, 20-30 per packet, 25 per packet, 20-40 per packet, 30 per packet, 20-50 per packet, 30-60 per packet, up to 60 per packet, up to 80 per packet, up to 100 per packet, up to 1000 per packet, or up to 2000 per packet, including all values ​​and sub-ranges therebetween.

[0406] The wave packet duration is determined by factors such as the cycle count. For matched pulse durations (or a sequence of positive and negative pulse durations in a biphasic waveform), a higher cycle count results in a longer wave packet duration and a greater amount of delivered energy. In some embodiments, the wave packet duration is in the range of approximately 50 to 1000 microseconds, such as 50 μs, 60 μs, 70 μs, 80 μs, 90 μs, 100 μs, 125 μs, 150 μs, 175 μs, 200 μs, 250 μs, 100 to 250 μs, 150 to 250 μs, 200 to 250 μs, 500 to 1000 μs, etc. In other embodiments, the wave packet duration is in the range of approximately 100 to 1000 microseconds, such as 150 μs, 200 μs, 250 μs, 500 μs, or 1000 μs.

[0407] The number of wave packets delivered during processing, or the wave packet count, typically includes 1 to 250 wave packets, including all values ​​and subranges therebetween. In some implementations, the number of wave packets delivered during processing includes 10, 15, 20, 25, 30, or more than 30 wave packets.

[0408] E. Suspension Period

[0409] In some implementations, the time interval referred to as the pause 406 between wave packets is set between approximately 0.001 seconds and approximately 5 seconds, including all values ​​and sub-ranges therebetween. In other implementations, the pause 406 ranges from approximately 0.01 to 0.1 seconds, including all values ​​and sub-ranges therebetween. In some implementations, the pause 406 is approximately 0.5 ms to 500 ms, 1 to 250 ms, or 10 to 100 ms, etc.

[0410] F. Batch

[0411] In some implementations, the signal is synchronized with the heart rhythm so that each wave packet is delivered synchronously within a specified time period relative to the heartbeat, thus the rest period coincides with the heartbeat. It is understood that the wave packets delivered within each specified time period relative to the heartbeat can be considered a batch or a bundle. Therefore, each batch has a desired number of wave packets so that the desired total number of wave packets is delivered at the end of the processing period. Each batch may have the same number of wave packets; however, in some implementations, batches may have different numbers of wave packets.

[0412] In some implementations, only one wave packet is delivered between heartbeats. In such cases, the rest period can be considered the same as the time interval between batches. However, when more than one wave packet is delivered between batches, the rest period is typically different from the time interval between batches. In such cases, the rest period is typically much shorter than the time interval between batches. In some implementations, each batch includes 1-10 wave packets, 1-5 wave packets, 1-4 wave packets, 1-3 wave packets, 2-3 wave packets, 2 wave packets, 3 wave packets, 4 wave packets, 5 wave packets, 5-10 wave packets, etc. In some implementations, the time interval for each batch is 0.5ms-1sec, 1ms-1sec, 10ms-1sec, 10ms-100ms, etc. In some implementations, the time interval between batches is variable depending on the patient's heart rate. In some cases, the time interval between batches is 0.25-5 seconds.

[0413] The tissue region is then processed until the desired number of batches are delivered to the tissue region. In some embodiments, each process delivers 2-50 batches, where a process is considered to be processing a specific tissue region. In other embodiments, processes include 5-40 batches, 5-30 batches, 5-20 batches, 5-10 batches, 5 batches, 6 batches, 7 batches, 8 batches, 9 batches, 10 batches, 10-15 batches, etc.

[0414] G. Switching time and silent time

[0415] like Figure 5As shown, the switching time is the delay or period of no energy delivery between the positive and negative peaks of the biphase pulse. In some embodiments, the switching time ranges from about 0 to about 1 microsecond, including all values ​​and subranges therebetween. In other embodiments, the switching time ranges from 1 to 20 microseconds, including all values ​​and subranges therebetween. In still other embodiments, the switching time ranges from about 2 to about 8 microseconds, including all values ​​and subranges therebetween.

[0416] A delay, referred to as a "quiet time," may also be inserted between each biphase cycle. The quiet time occurs within a wave packet but between biphase pulses. This contrasts with the rest period that occurs between wave packets. In other embodiments, the quiet time 412 ranges from approximately 0 to 0.5 microseconds, 0 to 10 microseconds, 2 to 5 microseconds, 0 to 20 microseconds, approximately 0 to approximately 100 microseconds, or approximately 0 to approximately 100 milliseconds, including all values ​​and subranges therein. In some embodiments, the quiet time 412 ranges from 0.2 to 0.3 microseconds. The quiet time can also be used to define the time interval between spaced-apart monophase pulses within a wave packet.

[0417] Delays such as switching time and silence time are introduced into the wave packet to reduce biphase cancellation effects within the waveform. In some cases, both switching time and silence time are increased to enhance the effect. In other cases, only switching time or only silence time is increased to induce such an effect.

[0418] G. Waveform

[0419] Figure 5 An embodiment of waveform 400 is illustrated, which has symmetrical pulses such that the voltage and duration of a pulse in one direction (i.e., positive or negative) are equal to the voltage and duration of a pulse in the other direction. Figure 6An example waveform 400 defined by another energy delivery algorithm 152 is illustrated, wherein waveform 400 has a voltage imbalance. Here, two wave packets are shown—a first wave packet 402 and a second wave packet 404, wherein wave packets 402 and 404 are separated by a rest period 406. In this embodiment, each wave packet 402 and 404 consists of a first biphase cycle (including a first positive pulse peak 408 with a first voltage V1 and a first negative pulse peak 410 with a second voltage V2) and a second biphase cycle (including a second positive pulse peak 408' with a first voltage V1 and a second negative pulse peak 410' with a second voltage V2). Here, the first voltage V1 is greater than the second voltage V2. The first biphase cycle and the second biphase cycle are separated by a silence time 412 between each pulse. Therefore, the voltage in one direction (i.e., positive or negative) is greater than the voltage in the other direction, and thus the area under the positive portion of the curve is not equal to the area under the negative portion of the curve. This unbalanced waveform may produce a more significant processing effect because the dominant positive or negative amplitude results in a longer duration of the same charge potential on the cell membrane. In this embodiment, the first positive peak 408 has a larger set voltage 416(V1) than the set voltage 416'(V2) of the first negative peak 410. Figure 7 Further examples of waveforms with unequal voltages are illustrated. Here, for simplicity, four different types of pulse packets are shown in a single diagram. The first pulse packet 402 consists of pulses with unequal voltages but equal pulse widths, and has no switching or silence time. Therefore, the first pulse packet 402 consists of four biphase pulses, each including a positive peak 408 with a first voltage V1 and a negative peak 410 with a second voltage V2. Here, the first voltage V1 is greater than the second voltage V2. The second pulse packet 404 consists of pulses with unequal voltages but symmetrical pulse widths (as in the first pulse 402), and the switching time is equal to the silence time. The third pulse packet 405 consists of pulses with unequal voltages but symmetrical pulse widths (as in the first pulse 402), and the switching time is less than the silence time. The fourth pulse packet 407 consists of pulses with unequal voltages but symmetrical pulse widths (as in the first pulse 402), and the switching time is greater than the silence time. It is understood that in some implementations, the positive and negative phases of the biphase waveform are not the same, but balanced, with the voltage in one direction (i.e., positive or negative) being greater than the voltage in the other direction, but the pulse length is calculated such that the area under the curve for the positive phase is equal to the area under the curve for the negative phase.

[0420] In some implementations, the imbalance includes pulses with pulse widths of unequal durations. In some implementations, the biphase waveform is unbalanced such that the voltage in one direction is equal to the voltage in the other direction, but the duration in one direction (i.e., positive or negative) is greater than the duration in the other direction, so that the area under the curve of the positive portion of the waveform is not equal to the area under the curve of the negative portion of the waveform.

[0421] Figure 8 Further examples of waveforms with unequal pulse widths are illustrated. Here, for simplicity, four different types of pulse packets are shown in a single diagram. The first pulse packet 402 consists of pulses with equal voltages but unequal pulse widths, and has no switching or silence time. Therefore, the first pulse packet 402 consists of four biphase pulses, each including a positive peak 408 with a first pulse width PW1 and a negative peak 410 with a second pulse width PW2. Here, the first pulse width PW1 is greater than the second pulse width PW2. The second pulse packet 404 consists of pulses with equal voltages but unequal pulse widths (as in the first pulse 402), and the switching time is equal to the silence time. The third pulse packet 405 consists of pulses with equal voltages but unequal pulse widths (as in the first pulse 402), and the switching time is less than the silence time. The fourth wave packet 407 consists of pulses with equal voltage but unequal pulse widths (as in the first pulse 402), and the switching time is longer than the silence time.

[0422] Figure 9 The illustration shows an example waveform 400 defined by another energy delivery algorithm 152, where the waveform is monophasic, a special type of imbalance where only the positive or negative portion of the waveform exists. Here, two wave packets are shown—a first wave packet 402 and a second wave packet 404—separated by a rest period 406. In this embodiment, each wave packet 402, 404 consists of a first monophasic pulse 430 and a second monophasic pulse 432. The first monophasic pulse 430 and the second monophasic pulse 432 are separated by a quiet period 412 between each pulse. Such a monophasic waveform can produce a more desirable treatment effect because the same charged cell membrane potential is maintained for a longer duration. However, compared to a biphasic waveform, a monophasic waveform provides greater stimulation to adjacent muscle groups.

[0423] Figure 10Further examples of waveforms with single-phase pulses are illustrated. Here, for simplicity, four different types of wave packets are shown in a single diagram. The first wave packet 402 consists of pulses with the same voltage and pulse width, and has no switching time (because the pulses are single-phase) and a quiet time equal to the active time. In some cases, the duration of the quiet time may be less than the active time of a given pulse. Thus, the first wave packet 402 consists of three single-phase pulses 430, each including a positive peak. In the case where the quiet time equals the active time, the waveform can be considered unbalanced, with a fundamental frequency representing a cycle period twice the active time and no quiet time. The second wave packet 404 consists of single-phase pulses 430 with equal voltage and pulse width (as in the first wave packet 402), and has a longer quiet time. The third wave packet 405 consists of single-phase pulses 430 with equal voltage and pulse width (as in the first wave packet 402), and has an even longer quiet time. The fourth wave packet 407 consists of a single-phase pulse 430 with the same voltage and pulse width (as in the first wave packet 402) and a longer silence time.

[0424] In some implementations, an unbalanced waveform is achieved by delivering more than one pulse in one polarity and then reversing it to an unequal number of pulses in the opposite polarity. Figure 11 Further examples of waveforms with such phase imbalances are illustrated. Here, for clarity, four different types of wave packets are shown in a single diagram. The first wave packet 402 consists of four cycles with equal voltage and pulse width; however, pulses of opposite polarity are mixed with single-phase pulses. Thus, the first cycle includes a positive peak 408 and a negative peak 410. The second cycle is single-phase, consisting of a single positive pulse without a subsequent negative pulse 430. This is repeated thereafter. The second wave packet 404 consists of mixed biphase and single-phase cycles (as in the first wave packet 402), however, the pulses have unequal voltages. The third wave packet 405 consists of mixed biphase and single-phase cycles (as in the first wave packet 402), however, the pulses have unequal pulse widths. The fourth wave packet 407 consists of mixed biphase and single-phase pulses (as in the first wave packet 402), however, the pulses have unequal voltages and unequal pulse widths. Therefore, multiple combinations and permutations are possible.

[0425] H. Waveform shape

[0426] Figure 12The illustration shows an example waveform 400 defined by another energy delivery algorithm 152, where the pulse shape is sinusoidal rather than square. Again, the figure shows two wave packets—a first wave packet 402 and a second wave packet 404—separated by a rest period 406. In this embodiment, each wave packet 402, 404 consists of three biphasic pulses 440, 442, 444. Moreover, these pulses 440, 442, 444 are sinusoidal rather than square. One advantage of the sinusoidal shape is that it is balanced or symmetrical, so that each phase has an equal shape. Balance can help reduce unwanted muscle stimulation. It will be understood that in other embodiments, the pulses have a decaying waveform.

[0427] Energy delivery can be actuated via various mechanisms, such as using a button 164 on catheter 102 or a foot switch 168 operably connected to generator 104. Such actuation typically provides a single energy dose. The energy dose is defined by the number of wave packets delivered and the voltage of the wave packets. Each energy dose delivered to the tissue maintains the temperature at or within the tissue below the thermal ablation threshold. Furthermore, the dose can be titrated or controlled over time to further reduce or eliminate heat buildup during treatment. The energy dose is not intended to induce thermal damage (defined as protein coagulation at sites at risk of treatment), but rather to deliver energy at a level that initiates treatment without damaging sensitive tissue.

[0428] Use of conventional ablation catheters

[0429] In some cases, it may be desirable to use a conventional ablation catheter in the tissue modification system 100 described herein. Using the devices, systems, and methods described herein, such a conventional ablation catheter can be used instead of catheter 102 to deliver the high-voltage pulsed electric field described herein alone, or in combination with the delivery of other energies, such as those used for conventional ablation. Example conventional ablation catheters include radiofrequency catheters commonly used to treat atrial fibrillation, radiofrequency catheters commonly used to treat other arrhythmias, microwave catheters, and other catheters. Examples include, but are not limited to:

[0430] 1) Catheters and devices from Abbott Laboratories (Chicago, IL), including Livewire. TM TC ablation catheter, Safire TM ablation catheter, Safire TM TX ablation catheter, Therapy TM ablation catheter, FlexAbility TM ablation catheter, Sensor Enabled TM FlexAbility TMIrrigation and ablation catheter, TactiCath TM Contact force irrigation ablation catheter, SensorEnabled TM TactiCath TM Quartz contact force ablation catheter, Therapy TM Cool Path TM ablation catheter;

[0431] 2) Catheters and devices from Biosense Webster Inc. (Irvine, CA), including SF one-way catheter, SF bidirectional catheter, One-way catheter bidirectional catheter, SF NAV one-way catheter SF NAV bidirectional catheter, SF NAV features a unidirectional catheter with curve visualization. SF NAV features a bidirectional catheter with curve visualization. One-way catheter bidirectional catheter, 4mm catheter DS catheter, RMT catheter, RMT 4mm catheter, SF one-way catheter, SF bidirectional catheter, EZ catheter, EZ 4mm bidirectional catheter, EZ DS bidirectional catheter, One-way catheter RMT catheter, 4mm tubing thermocouple, 4mm conduit thermistor 4mm braided tip catheter, CELSIUS 8mm unidirectional catheter, CELSIUS 8mm bidirectional catheter DS catheter, RMT catheter;

[0432] 3) Catheters and devices from Boston Scientific Corporation (Marlborough, MA) and / or BARD EP, including BLAZER PRIME. TM Temperature ablation catheter, BLAZERTM II Temperature Ablation Catheter Series, BLAZER TM Open irrigation temperature ablation catheter, INTELLANAV TM XP and Intellan Av MIFI TM XP Temperature Ablation Catheter Series, INTELLANAV TM ST ablation catheter, INTELLANAV TM Open irrigation and ablation catheter, INTELLATIP MIFI TM XP temperature ablation catheter, INTELLATIP MIFI TM Open irrigation and ablation catheter, INTELLANAV TM ST ablation catheter;

[0433] 4) Catheters and devices from Medtronic Inc. (Fridley, Minnesota), including 7Fr RF Marinr TM MC catheter, 5Fr RF Marinr TM catheter, RF contactor TM Catheter, RF Enhancer TM II catheter, RF conductor TM MC catheter;

[0434] 5) Access Point Technologies EP, Inc. (Rogers, MN) catheters and devices, including EPMap-iT TM Catheter, Map-iT TM Irrigation and ablation catheter;

[0435] 6) Catheters and devices from Synaptic Medical, Inc. (Lake Forest, CA), including Rithm Cool TM Irrigation of the tip ablation catheter, Rithm Deflectable ablation catheter Micro-infusion irrigation tip ablation catheter;

[0436] 7) Catheters and devices from Osypka Medical GmbH (Berlin, Germany) / Cardiotronic-Osypka Medical, Inc. (La Jolla, CA), including easy / easy TC, Cerablate Cerablate

[0437] 8) Catheters and devices from Biotronik GmbH & Co. (Berlin, Germany) and / or Acutus Medical Inc. (Carlsbad, CA), including AlCath Gold FullCircle, AlCath Flutter Gold, and AlCath Flux eXtra Gold;

[0438] 9) Catheters and devices from Atricure, Inc. (Mason, OH), including Isolator Synergy Clamps, Isolator Synergy Access Clamps, COBRA Fusion 150 Ablation System, Coolrail Linear Pen, Isolator Linear Pen, and Isolator Transpolar Pen;

[0439] 10) Catheters and equipment from OSCOR, Inc. (Palm Harbor, FL).

[0440] However, these conventional ablation catheters are not configured to deliver the high-voltage biphasic PEF energy described herein. In particular, many of these conventional catheters have features and mechanisms that fail under high-voltage energy delivery conditions. Such failure would render these features and mechanisms ineffective and could lead to overall device failure. For example, many conventional ablation catheters have multiple electrodes near their distal tip. Figure 13 An embodiment of a conventional ablation catheter 101 is illustrated, comprising a shaft 121 having a distal tip electrode 123 and a plurality of annular electrodes 127 proximal to the distal tip electrode 123. In this embodiment, the catheter 101 includes a contact force sensor 181 proximal to the distal tip electrode 123 and three internal fiber optic cables within the shaft 121. Furthermore, the catheter 101 includes an electromagnetic sensor 191 proximal to the distal tip electrode for integration with a cardiac mapping system. Additionally, the catheter 101 has a handle 129 disposed near the proximal end of the shaft 121. In this embodiment, the handle 129 includes a universal actuator design 131 that allows deflection independent of handle position and allows variable-controllable tension locking. The handle 129 has an integrated cable 133 for connection, such as for connection to a generator 108.

[0441] Since each electrode within conduit 101 is typically designed to be activated independently, each of electrodes 123, 127 has its own wire extending through the conduit to its proximal end. These wires are housed within the body of the conduit and are typically each surrounded by an insulating layer to prevent unwanted short circuits between the conductors.

[0442] However, these conventional ablation catheters 101 are prone to arcing and short circuits when delivering the pulsed electric field energy described herein. This is due to the high-voltage energy delivered through the individual conductors within the conventional catheter. Because the conventional ablation catheter 101 is designed for lower voltages, the leads are not arranged to insulate each other, and the insulation material used is insufficient to adequately insulate the leads under these conditions. Consequently, the insulation material fails, allowing the leads to short-circuit together and generate an arcing discharge within the catheter body. All these problems make such use undesirable or impossible for high-voltage energy delivery and for switching between high-voltage energy delivery and conventional energy (e.g., radio frequency, microwave, etc.).

[0443] Figure 14A The illustration shows the effect of using a conventional ablation catheter with multiple electrodes (such as...). Figure 13 This section discusses some issues related to high-voltage energy delivery using the catheter 101 shown. Here, the distal end of the catheter 101 is shown as having an elongated shaft 121 with a delivery electrode 123 at its tip. In this embodiment, the catheter 101 includes three additional annular electrodes: a secondary electrode 127a, a tertiary electrode 127b, and a quaternary electrode 127c, each electrode spaced incrementally proximally from the delivery electrode 123 along the shaft 121. During use, the delivery electrode 123 is positioned against a target tissue T, such as heart tissue. As shown, energy delivered via the delivery electrode 123 enters the tissue T. However, when processing heart tissue, the environment is typically filled with blood. Due to the conductivity of blood, energy is also transmitted via wires leading to the secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c, such as… Figure 14A As shown by the arrow in the image.

[0444] From the active electrode (voltage V = V0) to the ground electrode (V = 0), the voltage will decrease as the current (J) flows through the medium (blood or tissue) according to the conductivity (σ).

[0445]

[0446] This decay of the voltage applied across the entire dielectric results in a spatial distribution of potential. Since the unused electrodes are in contact with portions of the dielectric, a confined voltage can be expected in these portions.

[0447] The desired voltage in each electrode can be obtained using numerical methods. Analytical solutions are only feasible when using simple geometries and uniform conductivity. However, since both the microstructure and electrode geometry can be complex, it is more likely to use the finite element method and solve for the potential (V) satisfying the following Laplace equation to determine the voltage distribution.

[0448]

[0449] By using this method, the voltage distribution for the desired conduit geometry and environment can be calculated.

[0450] By using this method, the voltages of delivery electrode 123, secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c can be determined. Delivery electrode 123 has the highest voltage, and the voltage value decreases with distance from delivery electrode 123. Since all electrodes are connected to internal wires, the voltage of each of those electrodes can be extracted from the calculated values, thereby determining the maximum voltage difference between them. For example, if the energy delivered to delivery electrode 123 has a voltage of 3300V, the energy delivered to secondary electrode 127a will have a voltage of 1450V, the energy delivered to tertiary electrode 127b will have a voltage of 1050V, and the energy delivered to quaternary electrode 127c will have a voltage of 950V. This presents several problems. First, each of electrodes 123, 127a, 127b, and 127c is connected to the proximal end of conduit 101 via insulated wires. Figure 14B The diagram illustrates the cross-section of shaft 121, showing insulated wires 123', 127a', 127b', and 127c' corresponding to electrodes 123, 127a, 127b, and 127c. In conventional ablation catheters, such insulation is insufficient to insulate against voltage differences exceeding approximately 1500V (although this value may vary depending on the specific catheter design). Figure 14A In the example shown, the voltage difference between delivery electrode 123 and secondary electrode 127a is 1850V, the voltage difference between delivery electrode 123 and tertiary electrode 127b is 2250V, and the voltage difference between delivery electrode 123 and quaternary electrode 127c is 2350V. Each of these voltage differences exceeds the 1500V threshold that causes insulation failure, resulting in short circuits and arcing between the conductors.

[0451] Various systems and methods can be used to reduce the voltage below the threshold level for short circuits and / or arcing. For example, in some embodiments, each of electrodes 123, 127a, 127b, and 127c is set to the same voltage. Since each conductor will have the same potential, the voltage difference between the conductors is zero, and no arcing occurs. However, such a direct solution introduces several inconveniences. First, by activating all electrodes 123, 127a, 127b, and 127c in this manner, each electrode will deliver processing energy, potentially delivering energy to undesirable areas. Second, for the same applied voltage, the total current injected into the body is high, which may cause excessive increases in temperature or muscle stimulation. Furthermore, such high current requirements necessitate pulse generators with higher performance.

[0452] In other embodiments, a component network 111, such as that composed of passive components (e.g., resistors, inductors, and diodes), is used to modulate the energy flowing from the pulse generator to the electrodes. The passive components combine to form a complex impedance Z, which functions to guide energy through the conductor in a predetermined manner, thereby keeping the voltage difference below a specific threshold level, such as 1500V. In some embodiments, the component network 111 is disposed, for example, within the generator 108 to which the conduit 101 is coupled for energy delivery, within a separate device mated to the generator 108 (e.g., within the interface connector 10), or within the conduit 101 or an accessory thereof.

[0453] The values ​​of resistors, capacitors, and inductors used for impedance can vary depending on a variety of factors, including the frequency and amplitude of the applied electrical energy. For example, the impedance of an inductor is directly proportional to the applied frequency, while the impedance of a capacitor is inversely proportional to the applied frequency. For a given set of applied energy parameters, such as voltage, amplitude, and frequency, complex impedances can be predetermined to modulate the energy flowing from the pulse generator to the electrodes.

[0454] exist Figure 15 In one embodiment schematically illustrated, a first resistor R1 is positioned between wire 123' (coupled to delivery electrode 14) and wire 127a' (coupled to secondary electrode 127a). Similarly, a second resistor R2 is positioned between wire 123' (coupled to delivery electrode 123) and wire 127b' (coupled to tertiary electrode 127b). Furthermore, a third resistor R3 is positioned between wire 123' (coupled to delivery electrode 127) and wire 127c' (coupled to quaternary electrode 127c).

[0455] The resistance values ​​of resistors R1, R2, and R3 can vary depending on various factors, including the geometry and relative positions of the electrodes and the conductivity of the surrounding medium. For example, when a voltage is applied to the active electrode, the greater the distance between the active and inactive electrodes, the lower the induced voltage in the inactive electrode. When it is desired to keep the voltage difference between the active and inactive electrodes below a certain value, a larger distance between specific electrodes will involve a greater increase in the induced voltage in the corresponding inactive electrode to keep it within the constraint of the maximum allowable voltage difference. In an embodiment with a single inactive electrode, the proposed resistor can be tuned until the desired voltage is generated at that inactive electrode. However, in an embodiment with more than one inactive electrode, decreasing the value of one resistor will increase the current flowing through that inactive electrode and the induced voltage, but will also increase the voltage at other inactive electrodes. This interdependence between the resulting electrode voltages and resistance values ​​requires a highly complex system.

[0456] This complexity is addressed through a three-dimensional mathematical model of the electrodes and the underlying environment. This model takes into account the various elements expected in the environment when dealing with cardiac tissue, particularly tissue surrounded by blood. Therefore, the characteristics of these elements are specified and will determine the voltage distribution when a voltage is applied.

[0457] The mathematical model defines the voltage (V = V0) at the surface of the active electrode and the current source (I) at the inactive electrode. x It is defined as a current source (the integral of the normal current density J along its surface S) that depends on the voltage at the electrode surface, the voltage applied at the active electrode, and the selected resistance value.

[0458]

[0459] Using this model, potential combinations of resistance values ​​are determined (within a defined range and resolution). The final value that exhibits the desired performance is then selected. Figure 15 In the embodiment depicted, in which conduit 101 has four electrodes (one active electrode and three inactive electrodes), a combination of three resistance values ​​(R1, R2, R3) is calculated (e.g., from 0 to 1000 in 10Ω increments) to maintain a voltage difference below the maximum voltage difference supported by the conductor / insulation (e.g., 1500V) and a safe total current value for the pulse generator (e.g., below 40A).

[0460] In this example, the energy delivered to the delivery electrode 123 via wire 123' is 3500V. Similarly, in this embodiment, the total current has a maximum safe value of 40A. Therefore, in this embodiment, the total resistance network combination has a maximum value of 1000 to 1200 ohms. For example, in one embodiment, the resistance values ​​are as follows: R1 = 500Ω, R2 = 300Ω, and R3 = 300Ω. Using these resistance values, the voltage difference between the wires is shown in Table 1.

[0461] Table 1

[0462]

[0463]

[0464] Therefore, the resistor network is able to keep the voltage difference below the short-circuit and arc discharge thresholds (e.g., 1500V) while maintaining the desired high voltage energy delivery to the delivery electrode 123 (e.g., 3500V). It can be understood that in this example, the current through each wire is as shown in Table 2, and the total is approximately 40 amperes.

[0465] Table 2

[0466] Wire direction Current (A) Delivery electrode 123 27.9 Secondary electrode 127a 2.6 Triple electrode 127b 4.6 Quad-electrode 127c 4.8 total 39.9

[0467] In some cases, the use of resistor networks results in the creation of slightly smaller lesions in the target tissue (e.g., a reduction of up to 30%), potentially reducing the effectiveness of the treatment. However, this can be compensated for by increasing the treatment intensity (i.e., the voltage). This is possible because resistor networks also increase the threshold for arcing and short circuits. In some cases, resistor networks reduce the maximum current density by 20%. Therefore, the applied voltage can be increased by the same amount to compensate for this difference. Similarly, when using resistor networks, other waveform features can be added to modulate the treatment intensity, such as increasing the cycle count, lowering the fundamental frequency of the waveform, incorporating different degrees of asymmetry into the waveform, or adding additional wave packets.

[0468] Figures 16A-16B The illustration shows the use of Figure 15 The increase in the arc discharge threshold when the component network 111 is used. Figure 16A This corresponds to the case where component network 111 is not used. The figure illustrates the current values ​​for arc discharge occurring over a series of pulse cycles. Specifically, a certain amount of energy (e.g., 100 cycles) is delivered at a specific current value, and the presence or absence of arc discharge is observed. If no arc discharge is observed, the current value is increased. This continues until an arc discharge is observed. Therefore, the maximum value along the cycle vertices (e.g., 100 cycle vertices) is the arc discharge threshold. Thus, as... Figure 16AAs shown, when 60 cycles of energy are delivered through conduit 101 without component network 111, the threshold for arc discharge occurs at a current value of 22.2 amperes or 2100 V (which corresponds to the highest data point along the 60-cycle peak). Figure 16B Corresponding to the use of Figure 15 The component network 111 is shown, where R1 = 500, R2 = 300, and R3 = 300. Here, the figure illustrates the current value of the arc discharge occurring over a series of pulse cycles, which can be seen to be greater than... Figure 16A The value is 32.7 amps or 2700 V after 60 cycles. This corresponds to a 47% increase in the current threshold for arc discharge. Therefore, the use of the component network 111 significantly increases the arc discharge threshold by preventing uncontrolled current from flowing through the secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c.

[0469] It is understood that other systems and devices can be used to function in a similar manner to component network 111. For example, in some embodiments, generator 108 is configured to send appropriate current to the wires within conduit 101 in order to keep the voltage difference between the wires below a threshold that would cause arcing or damage to conduit 101. In some cases, generator 108 is configured for use with a specific conduit, such as the specific conventional radiofrequency conduits listed above. Therefore, the electrode spacing and other characteristics of the conduit are known. Consequently, generator 108 can be pre-programmed or pre-configured to deliver appropriate energy through each wire suitable for a specific conduit. For example, when delivered to Figure 15 When using the conduit 101 shown, a multi-channel generator can be used to drive the voltages of the secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c to a voltage lower than that of the distal electrode of the conduit, so as to keep the voltage difference between the leads below the arc discharge threshold (e.g., 1500V). This can be achieved using a multi-channel generator comprising two sets of capacitors: a primary set of capacitors is charged to drive energy delivery to the delivery electrode 123 of the conduit, and a secondary set of capacitors is charged to a voltage lower than that of the primary set of capacitors and drives energy delivery to the secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c. Furthermore, additional sets of capacitors can be used to drive different levels of energy to the secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c. In each of these cases, the voltage difference between the leads is kept below the arc discharge threshold (e.g., 1500V).

[0470] In some implementations, the generator is configured for use with a variety of catheters. In some cases, the generator can be programmed to be used with a specific catheter, where the user can indicate which catheter is being used. For example, the generator may display a variety of selectable options from a menu corresponding to known aspects of a known catheter or typical catheter, such as the number of electrodes, electrode spacing, catheter type, etc. Once the aspect to be identified is selected, the generator utilizes a pre-programmed algorithm corresponding to each type of known catheter or known set of features (e.g., electrode arrangement, etc.) to deliver an appropriate current to the wires within the catheter to keep the voltage difference between the wires below a threshold for arcing or damage to the catheter. In other implementations, the aspects of the catheter are identified by the generator. For example, in some cases, the catheter may be connected to the generator, where the generator is able to measure, sense, or identify aspects of the catheter that indicate the appropriate energy to be delivered through each wire. In some implementations, the generator delivers a dose of low-voltage energy through each wire to measure its corresponding impedance. The generator then delivers an appropriate current through each wire within the catheter based on the impedance measurement. In some implementations, the generator analyzes the catheter when it is in a treatment environment and / or in place to provide treatment. Therefore, environmental or situational factors affecting impedance readings are taken into account. This might include the presence of blood or other conductive fluids. Alternatively or additionally, this could include the location or arrangement of the device. For example, some devices may have electrodes along a surface (such as an arm) that can be positioned at various locations. Therefore, the distance between the individual electrodes can vary depending on the location of these surfaces. These aspects are taken into account by evaluating the device when it is located at the target location. This can result in a more accurate delivery of current values ​​through the wires during processing.

[0471] It is understood that such variability in environmental conditions can also be adapted through component network 111 instead of the generator itself. In such an implementation, component network 111 may consist of one or more potentiometers, rheostats, variable resistors, capacitors, inductors, diodes, etc. In other implementations, component network 111 may consist of multiple resistors, which can be selected by the controller as needed. In either case, according to Figure 15 The desired resistance is applied to each wire, where the R value (R1, R2, R3) is selected based on the measured value (such as the impedance value).

[0472] Furthermore, in some embodiments, the component network 111 and system described herein are used to shape the electric field delivered through conduit 101. For example, Figures 17A-17C The illustration shows various electric fields delivered by conduit 101 using different resistance values. Figures 17A-17CThe diagram illustrates a catheter 101, which has a delivery electrode 123, a secondary electrode 127a, a tertiary electrode 127b, and a quaternary electrode 127c near its distal end. Figure 17A In this configuration, conduit 101 is connected to component network 111 (equivalent to not being connected to component network 111) as shown in Figure 16, which has R1 = 10000Ω, R2 = 10000Ω, and R3 = 10000Ω. The resulting electric field 200 has a slightly circular shape, emanating primarily from delivery electrode 123. Figure 17B The diagram illustrates the connection of the same conduit 101 to, for example... Figure 15 The component network 111 has R1 = 500Ω, R2 = 300Ω, and R3 = 300Ω. The resulting electric field 200 is now transformed into a pear shape, having a slightly circular shape emanating from the delivery electrode 123 and the secondary electrode 127a, together with a smaller, overlapping slightly circular shape emanating from the tertiary electrode 127b and the quaternary electrode 127c to produce the pear shape. Figure 17C The same conduit 101 is illustrated, in which all electrodes are active. The resulting electric field 200 is now transformed into an elongated or elliptical shape extending from electrodes 123, 127a, 127b, and 127c. Therefore, the desired shape of the electric field 200 can be generated by selecting appropriate resistance values. This also affects the size of the resulting lesion, where the depth and width depend on the shape of the electric field 200.

[0473] As shown above, it can be understood that the component network 111 and system described herein can be used with a conduit 101 having a different number of electrodes than the examples provided herein, such as two electrodes, three electrodes, four electrodes, five electrodes, six electrodes, seven electrodes, eight electrodes, nine electrodes, ten electrodes, 2-4 electrodes, 2-5 electrodes, 2-10 electrodes, 10-15 electrodes, 2-20 electrodes, 2-30 electrodes, 2-40 electrodes, 2-50 electrodes, 2-60 electrodes, 2-70 electrodes, 2-80 electrodes, 2-90 electrodes, 2-100 electrodes, and more than 100 electrodes. Similarly, the component network 111 and system described herein can be used with a conduit 101 having an electrode arrangement different from the examples provided herein, such as electrodes with different spacing between electrodes and non-linear alignment, such as around a loop or on a branching spline, each containing one or more electrodes, etc. It can also be understood that if individual electrodes are adjacent to each other or close enough to be energized simultaneously, they can act as a single electrode. In such a case, the individual electrodes are considered as a single electrode and behave as a single electrode in the example provided in this paper.

[0474] It is also understood that the component network 111 and system described herein can also be used with catheters designed for bipolar energy delivery. Therefore, the PEF energy described herein can be delivered to target tissue using a bipolar energy delivery catheter used in a unipolar manner. In such a case, one of the electrodes on the bipolar energy delivery catheter is used as the delivery electrode, while the remaining electrodes are considered as auxiliary electrodes (i.e., secondary, tertiary, quaternary, etc.). Therefore, the component network 111 or system based on the same principle as described above can be used with a bipolar energy delivery catheter. Example bipolar energy delivery catheters are those supplied by Farapulse (Menlo Park, CA), Affera, Inc. (Watertown, MA), Atrian Medical (Galaway, Ireland), Kardium, Inc. (Burnaby, BC, Canada), etc.

[0475] It is understood that the component network 111 and system described herein can be used with any high-voltage energy, including high-frequency irreversible electroporation, pulsed radiofrequency ablation, nanosecond pulsed electric fields, etc. Other examples of high-voltage energy are described in U.S. Publication No. 20190201089, entitled "METHODS, APPARATUSES, AND SYSTEMS FOR THE TREATMENT OF PULMONARYDISORDERS", filed December 20, 2018; WO / 2019 / 133606, entitled "METHODS, APPARATUSES, AND SYSTEMS FOR THE TREATMENT OF DISEASE STATES AND DISORDERS", filed December 26, 2018; and WO / 2019 / 133608, entitled "OPTIMIZATION OF ENERGY DELIVERYFOR VARIOUS APPLICATIONS", filed December 26, 2018.

[0476] It is understood that the treatment catheters mentioned herein generally apply to a dedicated catheter 102 configured to deliver the PEF energy described herein, or to a conventional catheter 101 adapted for delivering the PEF energy described herein, such as a conventional catheter adapted with one or more accessories. Typically, such a treatment catheter is referred to as treatment catheter 102 for readability; however, it is understood that such a description applies to treatment catheter 101 in many or all contexts.

[0477] Tissue damage foci

[0478] When treating various cardiac conditions, a range of different target tissue thicknesses are encountered within the patient. Therefore, tissue lesions of varying depths may be desired. In some implementations, lesion size exhibits a highly repeatable and clearly monotonic trend due to the dose intensity of single-parameter operation. Thus, in some implementations, the resulting lesion size changes proportionally when a single parameter of the energy is changed. However, it is understood that the correlation between delivered energy and lesion depth can vary depending on various conditions, such as the size, shape, and configuration of the electrode arrangement, and the parameter values ​​and characteristics of the energy waveform. Therefore, in some implementations, the correlation is non-linear but follows a curve. For a given set of conditions, multiple optimal titration doses (e.g., via Algorithm 152) may be available to treat the expected range of target tissue thicknesses within the patient. Aspects considered in determining the final dose range include the cross-sectional width and depth of the target tissue, the risk of bubble formation, the expected time of treatment delivery, potential temperature rise, ECG waveform and rhythm maintenance, safety to the phrenic nerve and esophageal tissue, and the qualitative safety of the resulting treatment effect on the heart itself.

[0479] Table 3 summarizes the example dosages and their effects.

[0480] Table 3. Characterization of treatment dose and characteristics of resulting lesions

[0481]

[0482] Figure 18 A schematic diagram is provided of a treatment catheter 102 positioned for pulmonary vein isolation. Specifically, Figure 18 The figure illustrates a cross-section of the lumen L of the pulmonary vein PV, which is surrounded by cardiac tissue CT and subsequently by surrounding body tissue BT. In this figure, the diameter of the lumen L is 25 mm, and the thickness of the cardiac tissue CT is 4 mm. A treatment catheter 102 is shown with a delivery electrode 122 at its distal end; the delivery electrode 122 is illustrated as contacting the cardiac tissue CT via the lumen L. In this embodiment, electrode 122 delivers energy in a unipolar manner, with energy flowing outward from electrode 122 to the surface of the body tissue BT (e.g., skin) and a return electrode (not shown) positioned thereon. This electric field creates a treatment region A with a depth varying according to the energy delivery algorithm 152. In this example, a treatment region A penetrating 4 mm in thickness is obtained. It will be understood that, generally, the size of the treatment region A increases similarly with increasing energy. Figure 19 The graph (slashed line) illustrates an example of the correlation between energy and treatment depth, where a 4 mm lesion can be obtained with an energy output of approximately 1.5 joules. This is achieved by using, for example... Figure 18The local catheter shown is implemented using algorithm 152 to generate the energy waveform. It is understood that lesion depths greater than 4 mm, such as 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm and greater than 10 mm, can be achieved using the devices and methods provided herein. Figure 19 The relationship between energy and thermal effects is also illustrated as a flat line crossing the x-axis. Therefore, the delivered energy is non-thermal. As previously described, the therapeutic energy delivered via delivery electrode 122 is typically characterized by high-voltage pulses, which allows for the removal of target tissue with minimal or no damage to key anatomical structures, such as tissue-level structural proteins in the extracellular matrix. This prevents dangerous collateral effects such as stenosis and thrombosis.

[0483] The specific characteristics of the device and energy waveforms presented in this paper provide superior correlation between lesion depth and energy usage. Therefore, compared to other known PEF devices using known PEF energy, the device and system described herein are able to deliver deeper lesions using less energy. Less energy is associated with lower thermal effects and reduced requirements on the generator. In some implementations, this is a result of the current distribution properties. By delivering energy in a unipolar manner, energy can penetrate deeper into cardiac tissue CT compared to energy delivered in a bipolar manner. In the unipolar manner, the current flows directly through the tissue to the remote return electrode, extending deep into the myocardium. This contrasts with bipolar electrode pairs, where energy travels shallowly into the tissue and only returns to the terminal effector with the return electrode. Therefore, the energy does not propagate as deeply. The current will follow a path of least resistance, directed through the tissue, with little current penetrating deep into the tissue. Therefore, for bipolar electrode arrangements, a denser treatment scheme is required to achieve deeper treatment depths in the target tissue. This characteristic becomes more pronounced as the target depth increases (i.e., for such a design, going from 2 mm to 4 mm might require approximately 4 times the energy, while extending the treatment depth from 2 mm to 6 mm might require approximately 16 times the energy). Depending on the electrode configuration, some bipolar designs require up to 100 joules to achieve the same lesion depth and typically involve various negative side effects, such as overheating.

[0484] Understandably, although unipolar PEF energy can penetrate deeper into tissues than bipolar PEF or RF, nearby critical structures are protected from damage due to the nature of PEF energy and the presence of different tissue planes within cardiovascular anatomy. In particular, the pericardial fluid and pericardium surrounding the heart dissipate energy, thus protecting extracardiac structures such as the esophagus, phrenic nerve, coronary arteries, lungs, and bronchioles from injury. This is not the case when delivering energy that creates a lesion through thermal injury. In those cases, the propagation of conductive heat energy outside the target myocardial tissue can lead to thermal damage to non-target extracardiac structures. Figures 20-21 Mathematical modeling illustrates the effects of different conditions (such as...) Figure 13 The diagram shows the current distribution of PEF energy emitted by the delivery electrode 122 of the catheter 102. Here, the delivery electrode 122 is located inside the heart near the pericardium (PC), or outside the pericardium, such as in the esophagus (E). Figure 20 The diagram illustrates the current density distribution when all tissue is considered homogeneous. Therefore, the energy line is shown as undisturbed, emanating from the delivery electrode 122 and directly entering the surrounding tissue. However, Figure 21 The diagram illustrates the current density distribution under heterogeneous tissue conditions, taking into account differences in tissue types across different anatomical structures. As shown, energy lines are depicted pointing towards the pericardial PC, where they dissipate along the pericardial PC. Consequently, the energy reaching outside the pericardial PC is significantly reduced and insignificant to surrounding tissues (including the esophagus E). Figure 22 A graphical representation of current density versus penetration depth is provided for homogeneous and heterogeneous structures. The first curve, H, corresponds to homogeneous structures, where the decrease in current density at increasing structure depth follows a continuous asymptotic curve. The second curve, NH, corresponds to heterogeneous structures, as shown... Figure 21 The model provided illustrates how current density varies with tissue type at various depths.

[0485] It is understood that various different types of lesions can be created using the treatment catheter 102 described herein. As previously mentioned, lesion rings can be created using local catheters or single-dose catheters, such as around the pulmonary vein ostia. Furthermore, local catheters can be used to create many other types of lesions, particularly lines along various surfaces of cardiac tissue. In one embodiment, an inferior vena cava-tricuspid isthmus line is created to treat typical atrial flutter in the right atrium. In another embodiment, for patients with atrial fibrillation, particularly those with persistent atrial fibrillation, a top and bottom line is created to obtain a box-shaped lesion along the posterior wall of the left atrium. In another embodiment, for atypical atrial flutter, a mitral isthmus line is created along the anterior or lateral wall of the left atrium. In yet another embodiment, a ventricular line is created to connect two inexcitable boundaries crucial for the initiation or persistence of reentrant ventricular arrhythmias, which commonly occur in patients with ventricular tachycardia due to ischemic heart disease.

[0486] Contact and contact force

[0487] In some implementations, contact and contact force are evaluated to assess engagement and ensure uniform contact between the electrode and tissue. Known PEF devices and systems for treating cardiac tissue (such as atrial fibrillation) do not provide such evaluation. It has been asserted that PEF energy delivery depends solely on the proximity of the electrode to the target tissue, not on contact. The effects of PEF energy on tissue are considered proximity-dependent, not contact-dependent, as they are a result of the electric field extending from the electrode. These effects are thought to be a result of the delivered voltage and the distance over which the voltage is applied. Therefore, the effect at any given location within the tissue depends on the electric field strength.

[0488] However, these known PEF devices and systems rely on bipolar energy delivery that creates an electric field around the electrodes. In contrast, the devices, systems, and methods described herein primarily use a monopolar approach, driving the electric field toward a remote return electrode into the tissue. Lack of contact allows surrounding blood flow to diffract and disrupt energy flow, thus reducing penetration into the tissue. Therefore, improved contact increases the delivery of PEF energy into the tissue. Similarly, uniform contact optimizes such delivery.

[0489] Figures 23A-23B The effect of contact force on lesion size, particularly on lesion width and depth, is illustrated. Three contact force levels were evaluated: 1) low contact force 800 (5-15 g), 2) medium contact force 802 (15-30 g), and 3) high contact force 804 (30-50 g). Increasing the contact force had a beneficial effect on both the width and depth of the lesion. Figure 23AIn this study, the 28 amps of PEF energy, delivered to ventricular tissue in a monopolar configuration for 1.4 ms, resulted in a lesion depth of approximately 4 mm to 8 mm. The lesion depth was related to the contact force, with increased contact force leading to increased lesion depth. Figure 23B In this study, the 35 ampere PEF energy described herein was delivered to ventricular tissue in a monopolar configuration for 1.6 ms, resulting in a similar lesion depth between approximately 4 mm and 8 mm. Again, lesion depth is related to contact force, with increased contact force leading to increased lesion depth.

[0490] In some embodiments, the treatment catheter described herein includes a mechanism for measuring contact and / or contact force. In some embodiments, contact, particularly the impedance between the tip of catheter 102 and cardiac tissue, is sensed using an impedance sensor. Impedance is expressed as a complex number derived from resistance and reactance. In some embodiments, impedance is measured by sensing the impedance characteristics between electrodes on a local catheter, between electrodes on the catheter and individual remote electrodes located remotely from the body or heart, between electrodes on the catheter and multiple individual electrodes located remotely from the body or heart; or by a similar combination with a dedicated impedance sensor placed at the catheter tip or along the axis of the electrode to determine where electrode contact is desired.

[0491] In other implementations, contact force is sensed. This can be achieved through various mechanisms, summarized as follows: Figure 25 The contact force sensor 815 is shown. In some embodiments, the contact force is measured by detecting changes in a specific wavelength of light reflected in a fiber Bragg grating (FBG). In some embodiments, the contact force sensor 815 includes an optical sensor having at least one optical fiber mounted near the distal end of the conduit 102, wherein the distal end of the conduit is deformable. Light is provided through at least one optical fiber, and only light of a specific wavelength is reflected by the FBG. When a contact force is applied to the tip, the tip deforms the sensor body, and the compression or elongation of at least one optical fiber alters the periodic cycle of the R refractive index pattern. Such cyclical changes cause the wavelength of the reflected light to shift proportionally to the applied force. Thus, the direction and magnitude of the force are sensed. In some embodiments, the total value and magnitude of the axial and lateral component vectors of the contact force are provided to the user. In other embodiments, the contact force is measured by the compression or extension of a spring. In such an embodiment, the contact force sensor 815 includes a small spring mounted in the distal end of the conduit 102. The degree of spring compression and / or extension is detected at specific time intervals by at least one receiving sensor located at the base of the spring. The measured contact force value is then provided to the user. In some implementations, real-time values ​​(e.g., direction, force, etc.) are provided in graphical form or any suitable form.

[0492] Temperature sensing and control

[0493] The tissue-modifying system 100 described herein delivers a series of PEF batches or bundles over a period of time (such as several seconds). This accumulation of energy deposition results in a small amount of Joule heating—inherent in all PEF therapies as a byproduct of energy deposition. While acute, subacute, intermediate, and long-term histological data all indicated no substantial indication of thermal damage to tissues from the system, device, and method described herein, a specific assessment of the temperature changes resulting from the PEF energy delivery described herein was conducted. This assessment was performed by monitoring the output of a thermocouple embedded in the distal electrode tip of the catheter electrode using a handheld digital multimeter (Klein Tools, MM700). Video recordings of the multimeter readings were used to track the evolution of temperature changes in the catheter electrode during delivery. A treatment dose designed to achieve a treatment depth of 6.6 mm was delivered in the left atrium at a rhythm representing a patient's heart rate of 119 bpm. Figure 24 The resulting thermal profiles of the catheter electrode are provided. It can be seen that even at higher doses, the temperature never exceeds 45°C, well below the threshold (65°C) for rapid extracellular protein denaturation. It is also noted that the temperature recovers to within 1°C of baseline within approximately 5 seconds after reaching this peak temperature. Therefore, it is clear that thermal damage (extracellular protein denaturation) is not generated in cardiac tissue, thus reducing the chance of treatment-related adverse events and anatomical defects such as pulmonary vein stenosis. This also eliminates the formation of surface charring or thermal damage—which hinders energy delivery to underlying tissues and thus reduces the ability to generate transmural lesions.

[0494] However, it is understood that in some embodiments, system 100 includes temperature sensing and / or control measures for various purposes. In some embodiments, temperature is sensed and controlled to ensure that the temperature is maintained within the ranges of 30-65°C, 30-60°C, 30-55°C, 30-50°C, 30-45°C, and 30-35°C. Therefore, the lesion is not created by thermal damage because the tissue temperature remains below the threshold for thermal ablation. In some embodiments, temperature sensors are used to measure the electrode and / or tissue temperature during treatment to ensure that energy deposited in the tissue does not cause any clinically meaningful tissue heating. For example, in some embodiments, the temperature sensor monitors the temperature of the tissue and / or electrode, and if a predefined threshold temperature (e.g., 65°C) is exceeded, the generator changes its algorithm to automatically stop energy delivery or modifies the algorithm to reduce the temperature below the preset threshold. For example, in some embodiments, if the temperature exceeds 65°C, the generator reduces the pulse width or increases the time between pulses and / or wave packets (e.g., delivering energy every other heartbeat, every three heartbeats, etc.) in an attempt to reduce the temperature. This can occur via a predefined stepwise method, as a percentage parameter, or through other methods. It is understood that the temperature sensor can be positioned on electrodes (e.g., Figure 25 (as shown), at a suitable location near the electrode or along the distal portion of the conduit 102. Alternatively or additionally, the sensor may be positioned on one or more separate instruments.

[0495] In other implementations, temperature is sensed to evaluate lesion formation. This can be particularly useful when lesions are formed in the anatomical structure of a target tissue region with varying thicknesses. A rapid increase in temperature indicates that the lesion has penetrated the tissue depth and is nearing completion. Sensing such temperature changes can be especially useful when lesions are formed in thicker tissue or tissue of unknown depth.

[0496] In some embodiments, handling catheter 122 includes irrigation to help control the temperature of the delivery electrode 122 or surrounding tissue. In some cases, irrigation cools the delivery electrode 122, thereby allowing for more PEF delivery each time without increasing any potential thermally mediated damage. In some cases, irrigation also reduces or prevents clotting near the tip of catheter 102. It is understood that irrigation can be activated, increased, decreased, or stopped based on information from one or more sensors, particularly one or more temperature sensors.

[0497] Such cooling is achieved by delivering an isotonic saline solution via a lumen in conduit 102 through one or more irrigation ports at the distal end of conduit 102. The fluid can be a cooling fluid, a room temperature fluid, or a warm fluid. Fluid flow can be driven by various mechanisms, including gravity-driven drippers, peristaltic pumps, centrifugal pumps, etc. In some embodiments, irrigation has a flow rate of 0.1-10 ml / min, including 1 ml / min, 2 ml / min, 3 ml / min, 4 ml / min, 5 ml / min, or greater. In some embodiments, the flow rate is sensed by an electrical or mechanical flow sensing mechanism. In some embodiments, the temperature of the fluid is measured, while in other embodiments, the temperature of the fluid is modified, such as by heating or cooling, as the fluid is pumped into treatment conduit 102, for example, based on the measured temperature. In some embodiments, the fluid flow rate is determined based on the measured temperature of the tissue to be treated.

[0498] In some embodiments, the pump is electrically connected to generator 108, whereby generator 108 modifies the fluid flow rate based on the state of energy delivery to treatment conduit 102. For example, in some embodiments, the fluid flow rate increases during energy delivery. Similarly, in some embodiments, the fluid flow rate increases by a predetermined amount at a time before energy delivery and / or at one or more predetermined times during energy delivery. Alternatively or additionally, the fluid flow can be controlled by the user on demand. It is understood that the pump can be connected to generator 108 to operate at different speeds based on various aspects of energy delivery algorithm 152. In some embodiments, flow sensing and communication with generator 108 are used to prevent energy delivery when irrigation is not running. In other embodiments, the selection of energy delivery algorithm 152 is instead used to select a fluid flow rate suitable for energy delivery algorithm 152.

[0499] In some embodiments, at least one flushing port is located along the electrode and / or optionally, at least one flushing port is located along the shaft 120. In some embodiments, such as Figure 25As shown, the treatment conduit 102 includes a delivery electrode 122 in the form of a cylindrical "solid tip". In some embodiments, one or more irrigation ports 822 are located along the distal side of the cylindrical electrode tip. This allows fluid to be delivered directly from the distal tip of the conduit 102. In some embodiments, one or more irrigation ports 822' are located along the side surface of the cylindrical delivery electrode 122. In some embodiments, one or more irrigation ports 822" are located along the edge of the cylindrical delivery electrode 122, such as along the transition between the shaft 120 and the delivery electrode 122. This allows fluid to flow through the shaft 102 and subsequently over the exterior of the delivery electrode 122. It will be understood that the irrigation ports 822 can be located in multiple locations, including proximal to the shaft 120.

[0500] In some implementations, irrigation also mitigates the effects of large and microbubble formation. Gas embolism is a problem in many PEF therapies, particularly due to the potential for small “microbubbles” to form at the delivery electrode 122. Studies have shown that as little as 0.1 mL of air in the coronary arteries can cause myocardial injury. Larger bubbles are believed to have a higher probability of embolism, potentially leading to ischemic events, because smaller bubbles dissolve more easily in the return flow. Typically, microbubbles form on the electrode surface and increase in size as more energy is delivered. When a microbubble becomes large enough, it detaches from the electrode and drifts away. Irrigation at the electrode creates a flow of solution that detaches the bubble when it is small and can make it more easily dissolved before reaching the coronary artery. Therefore, an irrigation port 822 that allows fluid to flow through the exterior of the delivery electrode 122 is particularly helpful in reducing microbubble formation.

[0501] Interface connector

[0502] Conventional electroanatomical mapping (EAM) systems are frequently used to provide real-time 3D anatomical information to guide conventional catheter ablation without the drawbacks of radiation exposure or fluoroscopy. EAM systems typically use magnetic or impedance-based mapping algorithms, or a combination of both, to visualize and generate models and mapping maps (e.g., Biosense Webster / Johnson & Johnson). System, St. Jude Medical / Abbott's EnSite TM(Systems). Using these systems, electrophysiologists create real-time 3D representations of cardiac anatomy and electrical activity by positioning mapping catheters in various regions of the heart. The system tracks the catheter's position as the physician moves it with sweeping motions. During the procedure, a table on which the patient lies has a magnetic frame that generates a magnetic field, which tracks the catheter's movement via magnetic sensors within the catheter. Additionally, a patch on the patient's skin emits an electric current that allows the system to track impedance changes on the catheter's electrodes. Another EAM system—the KODEX-EPD system (Philips)—has been introduced, involving a newer approach to cardiac imaging to display real-time high-definition (HD) images to provide realistic anatomical structures and create voltage and activation mapping maps.

[0503] Because they can display images or data from other sources, electroanatomical mapping systems are sometimes called multimodal mapping or image integration systems. For example, computed tomography (CT) or magnetic resonance imaging (MRI) scans of the patient taken days or weeks before surgery can be loaded into EnSite. TM or The system then matches the 3D model of the heart with a real-time 3D model. This is achieved by using the system's image integration tools to identify and match unique cardiac structures between the 3D model and the CT / MRI scan. After identifying several common areas on the two images, the system merges / fuses the 3D model with the CT / MRI scan into a single 3D model. This process typically takes about 15 minutes; however, the localization of anatomical structures can change even within a week, so it may take longer if the preoperative scan does not readily correspond to a real-time view of the heart.

[0504] The electroanatomical mapping system also provides real-time data on electrical activity within the heart, allowing electrophysiologists to confirm that a conduction block has been achieved. In some cases, the system can provide other real-time information, such as atrial pressure and volume, to monitor the patient during surgery.

[0505] Therefore, the electroanatomical mapping system integrates at least three important functions: (a) non-fluorescent fluoroscopic localization of electrophysiological catheters in three-dimensional space; (b) analysis and 3D display of activation sequences calculated from local or computed electrograms, as well as 3D display of electrogram voltages; and (c) integration of such “electroanatomical” information with non-invasive images of the heart, such as computed tomography or magnetic resonance imaging.

[0506] In some embodiments, during electrophysiological (EP) procedures utilizing pulsed field energy as the processing energy, the electrodes of the cardiac processing catheter are used for multiple purposes. For example, in some embodiments, in addition to delivering PEF energy, the electrodes are also used to measure low-voltage intracardiac electrograms and / or to measure impedance for electroanatomical mapping systems. For this purpose, the electrodes of the cardiac processing catheter are simultaneously connected to a pulsed electric field generator and several EP devices (e.g., EP recording systems, electroanatomical mapping systems, such as…). EnSite TM (or KODEX-EPD). When these systems share the same electrical conductors, the signals from various devices may interfere with each other.

[0507] An interface connector is provided that minimizes interference between various devices connected to the contacts (e.g., electrodes, sensors, etc.) of the cardiac processing catheter. The interface connector includes a switching system that allows the EP signal amplifier (e.g., EP recording systems and electroanatomical mapping systems, such as...) to... when PEF energy is delivered via the catheter. Ensite TM Or KODEX-EPD) is isolated. In some implementations, such isolation is achieved using a high-voltage relay. When PEF energy is not delivered via a conduit, the PEF generator is similarly isolated from the EP signal amplifier, such as by using a high-voltage relay.

[0508] Figure 26 An example setup is illustrated, in which the interface connector 10 is used with an embodiment of the tissue modification system 100. In this embodiment, the tissue modification system includes a dedicated catheter 102 (however, a conventional catheter 101 for delivering PEF energy may be used alternatively), a high-voltage biphasic waveform generator 108, and at least one different energy delivery algorithm 152. It is understood that additional accessories and devices, such as an external cardiac monitor 110 connected to an external electrode 172 applied to the patient P to acquire an ECG, may be used. In this embodiment, the processing catheter 102 is designed to be monopolar, with at least one delivery electrode at its distal end, and a return electrode 106 positioned on the skin outside the body, typically in the thigh, lower back, or back. In this embodiment, the heart is accessed via the right femoral vein FV using a suitable access procedure such as the Seldinger technique. Typically, an introducer sheath 112 is inserted into the femoral vein FV, which acts as a conduit through which various catheters and / or tools, including the processing catheter 102, can be advanced. Figure 26As shown, the distal end of catheter 102 is advanced through the inferior vena cava, through the right atrium, through a transseptal puncture, and into the left atrium to access the pulmonary veins. In this embodiment, catheter 102 is used to perform cardiac mapping, which is the process of identifying the temporal and spatial distribution of myocardial potentials during a specific heart rhythm. Cardiac mapping during abnormal heart rhythms aims to elucidate the mechanisms of the rhythm, describe the propagation of activation within the region of interest from its initiation to its completion, and identify the initiation or critical sites of conduction as targets for treatment. Once the desired treatment location is identified, catheter 102 is used to deliver treatment energy.

[0509] In some embodiments, the proximal end of the treatment catheter 102 is electrically connected to the interface connector 10. Figure 26 In the illustrated embodiment, interface connector 10 is electrically connected to waveform generator 108 and a separate external device 12, such as a device capable of providing electroanatomical mapping procedures (e.g., System, Ensite TM (Systems, KODEX-EPD systems, etc.). Furthermore, as shown in this embodiment, the generator 108 is connected to an external cardiac monitor 110 to allow energy to be delivered in coordination with cardiac signals sensed from the patient P.

[0510] It is understood that in some cases, the interface connector 10 is directly connected to an electroanatomical mapping system, such as the patient interface unit of an electroanatomical mapping system, using cables. However, it is also understood that in other embodiments, the interface connector 10 may be connected, for example, using dedicated cables to a pin box, junction box, input / output box, terminal box, or other accessory, which in turn connects to the electroanatomical mapping system. The dedicated cable unravels multiple cables into individual component connectors or tip pins that can be inserted into a socket in the pin box. This allows individual access to each electrode. The pin box then connects to the electroanatomical mapping system. It is also understood that the interface connector 10 may include features of a pin box to eliminate the need for a separate pin box. Therefore, the interface connector 10 may include sockets for receiving tip pins and associated electronics.

[0511] Figures 27-28An embodiment of an interface connector 10 with a switching system 13 is illustrated. As shown, the proximal end of a catheter 102 is electrically connected to a first port 20 along the interface connector 10. The catheter 102 includes at least one electrode (e.g., a delivery electrode 122, and optionally, one or more additional electrodes 125) near its distal tip. The interface connector 10 includes a second port 22 for electrical connection to a separate external device 12 (such as an EP signal amplifier of an electroanatomical mapping system) and a third port 24 for electrical connection to a generator 108. The switching system 13 includes a path 30 and a branch path 32 of conductive wires or traces. The first port 20 is connected to the second port 22 via the path 30 of conductive wires or traces. The branch path 32 of conductive wires or traces branches from the electrical connection path 30 and connects to the third port 24. Each path 30, 32 includes at least one switch 36, 38, wherein opening the switch 36, 38 prevents a signal from passing through, while closing the switch 36, 38 allows a signal to pass through. Therefore, the signal flow between ports 20, 22, and 24 can be controlled by selectively opening and closing switches 36 and 38. For example, Figure 27 The diagram illustrates that switch 36 within path 30 is closed, allowing input signals (e.g., EP mapping signals or intracardiac electrocardiogram signals) from electrodes 122, 125 to be transmitted from catheter 102 to a separate external device 12, while switch 38 within path 32 is open to prevent electrical signals from being transmitted from generator 108 to electrodes 122, 125. Figure 28 The diagram illustrates that switch 38 within path 32 is closed, allowing processed energy from generator 108 (connected to port 24) to be delivered to electrodes 122, 125, while switch 36 within path 30 is open to prevent electrical signals from being transmitted to the separate external device 12 (connected to port 22). In some embodiments, each of switches 36, 38 is implemented using a corresponding high-voltage relay.

[0512] exist Figures 27-28In the diagram, conduit 102 is shown with four electrodes 122, 125, but alternatively may have more or fewer than four electrodes. Here, each of ports 20, 23, and 24 includes a separate electrical terminal corresponding to each of electrodes 122, 125, wherein each terminal provides an electrical connection between one of the electrodes 122, 125 and one of the conductive wires or traces within each of paths 30, 32. Similarly, each of paths 30, 32 includes a separate conductive wire or trace and a separate switch 36, 38 corresponding to each of electrodes 122, 125. All switches 36 within path 30 can be opened and closed simultaneously. Alternatively, one or more switches 36 within path 30 can be opened while one or more other switches 36 are closed, wherein only one or more of electrodes 122, 125 are used to sense the input signal. Similarly, all switches 38 within path 33 can be opened and closed simultaneously. Alternatively, one or more switches in switch 38 within path 32 may be turned on, while one or more other switches in switch 38 are turned off, wherein only one or more of electrodes 122 and 125 are used to deliver processing energy.

[0513] like Figure 28 As shown, when the second port 22 (e.g., electrically connected to the EP signal amplifier) ​​is disconnected during PEF energy delivery, the electrophysiologist cannot visualize the location of catheter 102 and view the intracardiac electrogram signal. Therefore, it is generally desirable to disconnect the second port 22 (e.g., electrically connected to the EP signal amplifier) ​​for a short period of time during which a portion of the energy (e.g., as a “wave packet”) is delivered.

[0514] The delivery of processing energy can be actuated by various mechanisms, such as by using a button on catheter 102 or a foot switch operably connected to generator 108. Such actuation typically provides a single energy dose. The energy dose can be defined at least in part by the number of wave packets delivered and the voltage of the wave packets. The energy dose can also be defined by, but is not limited to, the number of pulses within each wave packet and the pulse width of each pulse within each wave packet. In some embodiments, such processing energy delivery is synchronized with the heartbeat of patient P, such as by synchronizing wave packet delivery using an R-wave trigger from cardiac monitor 110. In some embodiments, switching of paths 30, 32 or relays is controlled based on an AND logic of the generator foot switch signal and the R-wave trigger signal from the cardiac monitor, such as... Figure 29As shown in the diagram. The high-voltage relay is only configured to deliver PEF energy and the EP signal amplifier is only isolated when both the foot switch and the R-wave trigger signal are enabled. In some embodiments, the R-wave trigger signal is enabled with a programmable delay after each R-wave is detected on the sensed intracardiac scan. In all other logical states with the foot switch and R-wave trigger enabled, the high-voltage relay is configured not to deliver energy and the generator 108 is isolated from all mapping signals and the intracardiac scan by opening switch 38, which is implemented as a relay.

[0515] In some implementations, the switching system 13 utilizes signal filtering instead of switching to perform the intended function. This typically depends on the frequency range of the various signals. For example, Figure 30 An embodiment of connector 10 is illustrated, which is adapted for use when the signal frequency between catheter 102 and the EP signal amplifier is lower than the PEF output. In this embodiment, the signal line to the EP signal amplifier includes a low-pass filter 40 to exclude high-frequency PEF energy. Similarly, the signal line between catheter 102 and generator 108 includes a high-pass filter 42 to exclude all low-frequency signals used by the electroanatomical mapping system and the EP recording system.

[0516] In some cases, it is desirable for conduit 102 to communicate with generator 108, for example, to deliver PEF energy, while simultaneously communicating with a separate external device 12, for example, to monitor contact force. If conduit 102 is not configured for such a situation, portions of conduit 102 (e.g., one or more electrodes, internal wiring, etc.) may overheat and / or fail. This can be mitigated by a variety of design features. In some embodiments, interface connector 10 is adapted to control the passage of signals in coordination with PEF energy delivery. For example, in some embodiments, conduit 102 is used for impedance sensing, ECG sensing, contact force sensing, and magnetism, etc. In such embodiments, several features can be used simultaneously without adverse effects. In some cases, impedance sensing and ECG sensing can be used with limited or no interference or negative impact on PEF delivery. Therefore, in some embodiments, specific signals can be allowed to pass during PEF energy delivery. This can be achieved by manipulating appropriate switches 36, 38. In this example, switches 36, 38 are both open along the paths of conductive wires or traces associated with impedance sensing and ECG sensing. In some implementations, specific signals are more likely to interfere with or adversely affect PEF delivery, such as signals associated with contact force sensing and magnetism. In such implementations, these signals can be blocked during PEF energy delivery. This can also be achieved by manipulating appropriate switches 36, 38. In this example, one or more of the switches 36 located within the path 30 along the conductive wires or traces associated with contact force sensing and / or magnetism are closed during PEF energy delivery or open otherwise. Similarly, one or more of the switches 38 located within the path 32 along these conductive wires or traces are open during PEF energy delivery or closed otherwise. It is understood that at any given time, any combination of features can be allowed or blocked by manipulating the switches 36, 38 or by alternative designs. It is also understood that, due to the nature of PEF delivery, such blocking of access to the electroanatomical mapping system may be so short-lived that the user may not notice it. For example, contact force sensing and / or imaging may be continuous to the user, occurring simultaneously with these blocking periods. It is understood that, in other implementations, one or more signals can be manipulated such that the catheter 102 can be electrically connected to the generator 108 and a separate external device 12 simultaneously.

[0517] Alternative locations, such as Figure 31As shown, signals unrelated to energy delivery or cardiac mapping can travel along paths separate from paths 30 and 32. For example, signals related to contact and / or contact force sensing can travel along conductive wires or traces 50, which are separate from paths 30 and 32 involved in the switching between generator 108 and external device 12. Here, contact and / or contact force sensing trace 50 extends from port 20 to port 23, which in turn connects to module 54 having components related to contact and / or contact force measurement. This separates activities related to contact and / or contact force sensing from energy delivery, mapping, etc. Similarly, signals related to temperature sensing can travel along conductive wires or traces 52, which are also separate from paths 30 and 32 involved in the switching between generator 108 and external device 12. Here, temperature sensing trace 52 extends from port 20 to port 23, which in turn connects to module 54 (or alternatively, a separate module) with components related to temperature measurement. This separates temperature sensing-related activities from energy delivery, calibration, etc.

[0518] In some implementations, particularly when using a conventional ablation catheter 101, a component network 111 is included in the interface connector 10, such as... Figures 32-33 As shown in the image. Figure 32 The diagram illustrates the relationship between... Figure 31 A similar implementation of interface connector 10 is used, in which a component network 111 is added. Here, the component network 111 is positioned between the switching system 13 and port 24 connected to the generator 108. This arrangement can be used when connecting the conduit 102 to a separate device for mapping and sensing (e.g., contact force sensing, temperature sensing, etc.). Therefore, the switching system 13 is positioned between port 20 and port 22. When the external device 12 includes Ensite... TM Electroanatomical mapping system and module 54 include Tactisys TM This is especially true for systems that provide components for monitoring contact force and temperature. Similarly, Figure 33 The diagram illustrates a network of components 111 positioned between the switching system 13 and port 24 connected to the generator 108. However, such an arrangement can also be used when the conduit 102 is connected to a single device providing mapping and sensing (e.g., contact force sensing, temperature sensing, etc.). Again, the switching system 13 is positioned between ports 20 and 22; however, port 23 is eliminated, thus the contact and / or contact force sensing trace 50 and the temperature sensing trace 52 extend from port 20 to port 22. When the external device 12 includes... This is especially true when using electroanatomical mapping systems (which include components for monitoring contact force and temperature).

[0519] Figure 34 An embodiment of a tissue modification system 100 for a patient (not shown) is illustrated, which includes a treatment catheter (dedicated catheter 102 or conventional ablation catheter 101), a return electrode 106, a foot switch 168, an interface connector 10, a waveform generator 108, a separate external device 12 (e.g., with the ability to provide electroanatomical mapping procedures), an external cardiac monitor 110, and various other accessories including a needle cartridge 171. Figure 35 The illustration shows an embodiment of a tissue modification system 100 for patient P, wherein the treatment catheter includes a specific conventional RF catheter 101 and a Tacticath. TM Ablation catheter. Again, system 100 includes a return electrode 106, a foot switch 168, an interface connector 10, a waveform generator 108, a separate external device 12 (e.g., capable of providing electroanatomical mapping procedures), an external cardiac monitor 110, and various other accessories including a needle cartridge 171. Furthermore, system 100 includes module 54, which includes a Tactisys for contact force and temperature acquisition. TM system.

[0520] System 100 produces easily visualized treatment effects in real time while monitoring treatment delivery and progress. In some cases, strong attenuation of the ECG signal is clearly visible at the treatment catheter after treatment delivery. Furthermore, in some embodiments, voltage mapping is performed before and after single-site treatment, where changes in the voltage mapping graphs clearly confirm the operation of the 3D mapping system and its ability to track delivery progress when treatment sites are connected to generate continuous conduction-blocking lesions.

[0521] Alternative treatment catheter design

[0522] The systems and devices described herein can alternatively be used with a variety of other types and styles of treatment catheters 102. In some embodiments, the treatment catheter 102 is designed to deliver local treatment, while in other embodiments, the treatment catheter 102 is designed to deliver “single-delivery” treatment. Local treatment is considered to be a therapy in which energy is delivered sequentially, such as repeatedly applying energy in a point-by-point manner around a pulmonary vein to create a circular treatment zone, as previously described in Figure 4 As shown in the diagram. Single-delivery therapy is considered a therapy in which energy is delivered to the entire periphery of the pulmonary vein inlet via a delivery electrode in a “single-delivery” manner; however, such deliveries can be repeated if desired. If desired, this may optionally include rotation of electrode 122 between “deliveries”.

[0523] Local treatment

[0524] As previously mentioned, local treatment is typically performed using a delivery electrode 122 with a cylindrical shape having a distal side, such as Figures 2A-2B As shown in the diagram. In some embodiments, the distal side of the delivery electrode 122 has a diameter of 3 mm. In such an embodiment, when the treatment catheter 102 is positioned perpendicular to the tissue and its distal side is positioned against the tissue, the surface contact area is approximately 7 mm². 2 When delivering PEF energy as described herein, such as with the following parameter values: 3300V / 400kHz / 40 cycles / 30 packets, 3300V / 400kHz / 30 cycles / 10 packets, 2000V / 400kHz / 40 cycles / 30 packets, each energy packet delivers 15 joules of energy. In such cases, the delivery electrode has a diameter of approximately 2 mm. 2 The current density.

[0525] It is understood that local treatments can be delivered using alternative catheter designs and methods. For example, in some embodiments, the treatment catheter 102 is configured to provide local treatments, such as according to International Patent Application No. PCT / US2018 / 067504 entitled “OPTIMIZATION OF ENERGYDELIVERY FOR VARIOUS APPLICATIONS,” which claims priority to Provisional Patent Application No. 62 / 610,430, filed December 26, 2017, and U.S. Provisional Patent Application No. 62 / 693,622, filed July 3, 2018, which are incorporated herein by reference in their entirety for all purposes.

[0526] Single-dose treatment

[0527] Figure 36 An embodiment of a treatment catheter 102 configured to deliver “single-drop” therapy is illustrated. Single-drop therapy is considered to be a therapy in which energy is delivered in a “single-drop” manner to the periphery of the entire treatment area, such as the pulmonary vein inlet, via a delivery electrode, however, such delivery can be repeated if desired. If desired, this may optionally include rotation of the electrode 122 between “drops”.

[0528] In this embodiment, the catheter 102 includes an elongated shaft 120 having a delivery electrode 122 located near its distal end 124 and a handle 126 located near its proximal end 128. Here, the delivery electrode 122 is configured to deliver energy to a larger area, such as the entire treatment area, particularly to create a continuous treatment area around the pulmonary vein to block conduction. In this embodiment, the delivery electrode 122 has a cup-shaped or funnel-shaped shape facing distally. The diameter of the imprint created by the delivery electrode 122 is larger than the diameter of the imprint created by the local treatment catheter. This is to achieve a specific treatment in a single application. Thus, in some embodiments, treatment is provided in a single application of the electrode 122 to the tissue; however, it is understood that in some cases, energy can be applied more than once if desired. The handle 126 is used to manipulate the catheter 102, particularly guiding the distal end 124 during delivery and treatment. Energy is provided to the catheter 102 via a cable 130 connectable to the generator 108, and thus to the delivery electrode 122.

[0529] Figures 37A-37B A similar embodiment of a delivery electrode 122 configured to deliver a "single-dose" treatment is illustrated, wherein the delivery electrode 122 has a cup-shaped or funnel-shaped form. In this embodiment, the electrode 122 includes a plurality of filaments 140 forming an expandable half-basket, wherein at least one of the filaments acts as the delivery electrode. In this embodiment, the half-basket is attached to the shaft 120 near its proximal end 142 and has a circular open shape at its distal end 144 (i.e., the free end). Thus, in the expanded configuration, the half-basket shape has a circular edge 146 formed along its distal end 144. In this embodiment, the filaments 140 are bent along the edge 146 to create a non-invasive surface. Figure 37B Provided Figure 37A An end view of the embodiment is shown. As illustrated, the edge 146 has a circular shape, while the remainder of the half-basket has a woven appearance as it narrows towards the shaft 120. It is understood that the multiple threads 140 can be woven or interlaced into various configurations. It is also understood that the delivery electrode 122 can be self-expanding, wherein the electrode 122 is in a collapsed configuration when held within the sheath, and self-expands to an expanded configuration when the sheath is removed. It is also understood that the delivery electrode 122 can alternatively expand via other mechanisms, such as by the inflation of the delivery balloon.

[0530] Figures 38A-38B The illustration shows the application of [something] to surfaces such as cardiac tissue regions. Figures 37A-37BThe delivery electrode 122. In these illustrations, electrode 622 is shown as a contact stage to illustrate its shape change during increased applied contact force. It can be understood that a similar shape change occurs when contacting tissue, particularly cardiac tissue surrounding the pulmonary veins. The circular opening of the pulmonary vein can be seen aligned within the circular shape of edge 146, thus the delivery electrode 122 contacts the tissue surrounding the opening of the pulmonary vein. Figure 38A The diagram illustrates electrode 122 positioned against a surface, with edge 146 in contact with that surface. Here, electrode 122 essentially retains its free state, having a funnel-shaped form. Figure 38B The diagram illustrates electrode 122 under increased pressure on the surface. This causes a portion of the filaments 140 to collapse together, forming a larger edge 146. Therefore, during the application of pressure or contact force, the energy delivered along the edge 146 by the multiple filaments 140 is greater, at least due to the increase in the number of filaments 140 along the edge 146, compared to when minimal pressure or contact force is applied. It can be understood that... Figure 38B The illustration depicts a situation where near-maximum pressure or contact force is applied, in which the half-basket almost completely collapses, creating a short funnel shape. It can be understood that the half-basket shape accompanies both configurations (i.e., Figure 38A and Figure 38B Different configurations between them can apply a variety of different levels of pressure or contact force.

[0531] In some embodiments, at least a portion of one of the plurality of filaments is insulated from nearby filaments. In some embodiments, at least a portion of one of the plurality of filaments is insulated, leaving exposed portions of the filaments to create an active region that concentrates energy at a specific location along the target tissue. In some embodiments, the plurality of filaments may be energized simultaneously. In other embodiments, at least some of the plurality of filaments may be energized individually. In some embodiments, the delivery electrode 122 includes an insulating material covering at least a portion of the plurality of filaments 140. Figure 39 The diagram shows... Figures 38A-38B In one embodiment of the delivery electrode 122 shown, a portion of a plurality of filaments 140 is covered by an insulating material 150. In this embodiment, the insulating material 150 substantially covers a semi-basket-shaped portion that does not collapse or minimally collapses into the edge 146 when force is applied to the tissue. Thus, the insulating material 150 covers a portion of the proximal end 142 of the delivery electrode 122. This allows more energy to be delivered to the distal end 144 of the delivery electrode 122, particularly the edge 146, because energy is not dissipated into the environment via the proximal end 142.

[0532] Figure 40AA schematic cross-sectional view of the lumen L of the pulmonary vein PV is provided, which is surrounded by cardiac tissue CT and subsequently by surrounding body tissue BT. In this figure, the lumen L has a diameter of 25 mm, and the cardiac tissue has a thickness of 4 mm. The treatment catheter 102 is shown with a delivery electrode 122 at its distal end; the electrode 122 is illustrated to simultaneously contact the cardiac tissue CT at various locations via the lumen L. It can be understood that in this example, the delivery electrode 122 has a full basket shape and is inserted into the lumen L. However, in other embodiments, a half basket shape can be seen inserted into the lumen L, or the edge 146 can be positioned against the tissue surrounding the lumen L.

[0533] In this embodiment, the conduit 102 delivers energy in a unipolar manner, with energy flowing outward from the delivery electrode 122 to the surface of the body tissue BT (e.g., skin) and a return electrode (not shown) located thereon. This electric field creates treatment regions A of varying depths according to the energy delivery algorithm 152. In this example, a treatment region A penetrating 4 mm in thickness is obtained. It will be understood that, generally, the size of the treatment region A increases with increasing energy. Figure 40B The graph (slashed line) illustrates an example of the relationship between energy and processing area depth. Figure 40B The diagram also illustrates the relationship between energy and thermal effects, represented by a horizontal straight line crossing the x-axis. Therefore, the delivered energy is non-thermal.

[0534] Another type of delivery electrode 122, configured to deliver “one-shot” treatment, has an annular shape. Typically, the annular shape consists of one or more rings arranged to form a continuous circular edge. Figure 41 An embodiment of a delivery electrode 122 including an initial single loop is illustrated. In this embodiment, the electrode 122 is formed of shape memory wire 160, which is capable of twisting and folding back on itself during delivery to create a substantially circular edge 162. Thus, due to the folding action, the initial single loop forms a secondary loop 165 extending around the edge 162, so the circular edge 162 is substantially composed of two layers of wire 160. In this embodiment, the secondary loop 165 extends around almost the entire circumference of the edge 162 (i.e., the initial loop and the secondary loop 165 together form the edge 162); therefore, more than half of the circumference of the edge 162 is composed of two layers of wire. Figure 42 As shown in the figure, the rounded edge 162 is typically substantially perpendicular to the shaft 120 during deployment. Figure 41The image depicts a side view of the delivery electrode 122. This allows the edge 162 to be positioned against the cardiac tissue surrounding the pulmonary vein inlet. Therefore, energy is delivered via the delivery electrode 122 in a “single-pour” manner to the entire perimeter of the pulmonary vein inlet; however, such deliveries can be repeated if desired. If desired, this may optionally include rotation of the electrode 122 between “pours.” In this embodiment, the shaft 120 is biased and not concentric with the circular edge 162; however, it will be understood that in other embodiments the shaft 120 is concentric with the edge 162.

[0535] Figures 43A-43E The diagram shows... Figures 41-42 Deployment of the delivery electrode 122. In this embodiment, the delivery electrode 122 is configured to be received within the shaft 120; however, it is understood that, alternatively, a sheath may be advanced over the catheter 102 to capture the electrode 122. Initially, when received within the shaft 120, the electrode 122 unfolds and flattens into a relatively straight configuration. This allows the electrode 122 to collapse into a smaller configuration to allow for advancement of the shaft 120 with a smaller outer diameter through the vascular system. In this embodiment, the electrode 122 is deployed by advancing it from the shaft 120. Figure 43A The diagram illustrates an electrode 122, advanced from the distal end of shaft 120 and having an initial straightened configuration. This is the initial ring. It can be understood that... Figures 43A-43E The deployment steps shown are from still images of a video, where each step occurs rapidly and sequentially. Therefore, electrode 122 self-configures into a deployment configuration upon release. Figure 43B The illustration shows electrode 122 beginning to fold downwards onto itself, thus revealing its annular shape. In this embodiment, the farthest portion 170 of the ring bends and curls backwards in a proximal direction toward the shaft 120. Figure 43C The illustration shows the outermost portion 170 bending further downwards to form a V-shape. This V-shape is the initial stage for creating the two layers of threads at the edge 162. Figure 43D The illustration shows the transformation of electrode 122 from a V-shape to a double-ring. This step occurs so rapidly that it is not visible to the naked eye. In this embodiment, the V-shaped portions intersect each other in a twisting and folding manner to form a double ring from a single ring. Figure 43E The diagram illustrates the final configuration of electrode 122 in its fully deployed state. Here, the loops of wire 160 have formed a circular edge 162 and are essentially composed of two layers of wire 160. As shown, the circular edge 162 is generally perpendicular to the shaft 120 during deployment.

[0536] Figures 44A-44B Another embodiment of the delivery electrode 122 is illustrated, which includes a loop of shape memory wire 160 forming a substantially circular edge 162. (See illustration.) Figure 44AAs shown in the diagram, in this embodiment, the two rings 165a and 165b overlap, forming a circular edge 162 together. The two rings 165a and 165b... Figure 44B The loops are separated for visualization purposes. In this embodiment, each of the two rings 165a and 165b forms an arc 167 that spans approximately 270 degrees of the circle surrounding the shaft 120. Therefore, the circular edge 162 consists of two layers of thread 160 in the two overlapping portions of the rings 165a and 165b. In this embodiment, the overlapping area extends about half the circumference of the edge 162 (each ring 165a and 165b extends about one-quarter of the opposite portion of the circumference of the edge 162). Therefore, about half the circumference of the edge 162 consists of two layers of thread. However, it is understood that the rings 165a and 165b can be configured to cover different portions of the circumference of the edge 162, including almost the entire edge. Figure 45 As shown in the figure, the rounded edge 162 is typically substantially perpendicular to the shaft 120 during deployment. Figure 44A The image depicts a side view of the delivery electrode 122. This allows the edge 162 to be positioned against the cardiac tissue surrounding the pulmonary vein inlet. Therefore, energy is delivered via the delivery electrode 122 in a “single-pour” manner to the entire perimeter of the pulmonary vein inlet; however, such deliveries can be repeated if desired. If desired, this may optionally include rotation of the electrode 122 between “pours.” In this embodiment, the shaft 120 is biased and not concentric with the circular edge 162; however, it will be understood that in other embodiments the shaft 120 is concentric with the edge 162.

[0537] Figure 46A Another embodiment of the delivery electrode 122 is illustrated, which includes loops of shape memory wires 160 that are gathered together to create a substantially circular edge 162. In this embodiment, the electrode 122 consists of three loops 165a, 165b, and 165c that extend at least partially around the edge 162, thus the circular edge 162 is composed of two layers of wires 160 in three portions. The three loops 165a, 165b, and 165c in... Figure 46B The sections are separated for visualization. In this embodiment, each of the three rings 165a, 165b, and 165c forms an arc 167 that spans approximately 270 degrees of the circle surrounding the shaft 120. Therefore, the circular edge 162 consists of three layers of threads 160 in the three overlapping sections of the rings 165a, 165b, and 165c. In this embodiment, the overlapping area extends around almost the entire circumference of the edge 162. In this embodiment (each ring 165a, 165b, and 165c extends around approximately one-third of the circumference of the edge 162), therefore, approximately the entire circumference of the edge 162 consists of two layers of threads. Figure 47 As shown in the figure, the rounded edge 162 is typically substantially perpendicular to the shaft 120 during deployment. Figure 46A The image depicts a side view of the delivery electrode 122. This allows the edge 162 to be positioned against the cardiac tissue surrounding the pulmonary vein inlet. Therefore, energy is delivered via the delivery electrode 122 in a “single-pour” manner to the entire perimeter of the pulmonary vein inlet; however, such deliveries can be repeated if desired. If desired, this may optionally include rotation of the electrode 122 between “pours.” In this embodiment, the shaft 120 is biased and not concentric with the circular edge 162; however, it will be understood that in other embodiments the shaft 120 is concentric with the edge 162.

[0538] The detailed description above includes reference to the accompanying drawings, which form part of the detailed description. The drawings illustrate, by way of illustration, specific embodiments in which the invention may be practiced. These embodiments are also referred to herein as “examples.” Such examples may include elements other than those shown or described. However, the inventors also contemplate providing examples of only those shown or described elements. Furthermore, the inventors contemplate examples of any combination or arrangement of those described or described elements (or one or more aspects thereof), whether relating to a particular example (or one or more aspects thereof) or to other examples (or one or more aspects thereof) described or described herein.

[0539] In the event of any inconsistency between the usage in this document and any other document incorporated by reference, the usage in this document shall prevail.

[0540] In this document, as is common in patent documents, the terms “a” or “an” are used to include one or more, and are not related to any other instance or use of “at least one” or “one or more”. In this document, the term “or” is used to indicate a non-exclusive or, therefore “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise stated. In this document, the terms “comprising” and “wherein” are used as their concise English equivalents. Furthermore, in the following claims, the terms “comprising” and “including” are open-ended, meaning that a system, device, article, composition, formulation, or process that includes elements other than those listed after the term in a claim is still considered to be within the scope of that claim. Additionally, in the following claims, the terms “first,” “second,” and “third,” etc., are used merely as labels and are not intended to impose numerical requirements on their objects.

[0541] The above description is intended to be illustrative and not restrictive. For example, the examples (or one or more aspects thereof) described above may be used in combination with each other. Other embodiments may be used, for example, by those skilled in the art upon reading the above description. An abstract is provided to conform to 37C.FR §1.72(b) to enable the reader to quickly determine the nature of the technical disclosure. It is understood that this submission is not intended to construe as limiting the scope or meaning of the claims. Furthermore, various features may be combined in the above detailed description to simplify this disclosure. This should not be construed as meaning that any unclaimed disclosed feature is essential to any claim. Rather, the subject matter of the invention may not be limited to all features of a particular disclosed embodiment. Therefore, the following claims are incorporated herein by way of example or embodiment, each claim existing independently as a separate embodiment, and these embodiments are contemplated to be combined with each other in various combinations or arrangements. The scope of the invention should be determined by reference to the appended claims and the full scope of their equivalents.

Claims

1. A system for creating lesions in a region of cardiac tissue of a patient, comprising: a catheter; a signal generator connected to the catheter, wherein the signal generator comprises at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through the catheter in order to create the lesions in the region of cardiac tissue; and a subsystem for use with the catheter connected to the signal generator, wherein the catheter comprises a catheter body comprising a distal portion and a proximal portion, the distal portion of the catheter body comprising a plurality of electrodes electrically isolated from one another, the proximal portion of the catheter body comprising a plurality of terminals and connectable to the signal generator in order to enable delivery of the pulsed electric field energy via selected one or more of the electrodes, and the catheter further comprising a first plurality of electrically conductive wires, wherein each electrically conductive wire electrically couples a different one of the electrodes to a different respective one of the terminals, wherein the subsystem comprises a second plurality of electrically conductive wires leading out of the subsystem and arranged to direct a voltage to adjacent ones of the second plurality of electrically conductive wires of the subsystem, the second plurality of electrically conductive wires electrically connected to the first plurality of electrically conductive wires; wherein the subsystem further comprises a network of components comprising the second plurality of electrically conductive wires and configured to maintain a potential difference between the one or more electrodes of the catheter selected for delivery of the pulsed electric field energy and one or more other electrodes of the catheter not selected for delivery of the pulsed electric field energy below a threshold potential difference that prevents arcing between one or more pairs of the first plurality of electrically conductive wires by maintaining a voltage difference between adjacent ones of the second plurality of electrically conductive wires below the threshold potential difference, thereby permitting non-thermal use of the cardiac tissue, wherein the network of components comprises a plurality of resistors, wherein each resistor of the plurality of resistors is disposed between an electrically conductive wire of the first plurality of electrically conductive wires electrically coupled to an electrode selected for delivery of the pulsed electric field energy and another electrically conductive wire of the first plurality of electrically conductive wires electrically coupled to an electrode not selected for delivery of the pulsed electric field energy.

2. The system of claim 1, wherein the pulsed electric field energy comprises biphasic pulses in wave packets.

3. The system of claim 1, wherein the pulsed electric field energy has a voltage of at least 2000 V.

4. The system of claim 1, wherein the pulsed electric field energy delivered by the signal generator comprises energy in excess of a predetermined voltage level, wherein the subsystem prevents arcing between one or more pairs of the first plurality of electrically conductive wires.

5. The system of claim 4, wherein the predetermined voltage level comprises 1000-1500 volts.

6. The system of claim 1, wherein the catheter comprises a radiofrequency ablation catheter.

7. The system of claim 1, further comprising an external return electrode electrically couplable to the signal generator, and wherein the catheter delivers stimulation energy in a monopolar manner using the external return electrode.

8. The system of claim 1, further comprising an interface connector that electrically couples the catheter to both the signal generator and an electroanatomical mapping system, wherein the interface connector prevents the delivery electrode from being in electrical communication with both the signal generator and the electroanatomical mapping system at the same time.

9. The system of claim 8, wherein the interface connector comprises a switch system that includes a first path of at least one wire between the delivery electrode and the signal generator and a second path of at least one wire between the delivery electrode and the electroanatomical mapping system, wherein the switch system switches energy transmission between the first path and the second path.

10. A system for creating lesions in a region of cardiac tissue of a patient, comprising: a catheter; a signal generator connected to the catheter, wherein the signal generator comprises at least one energy delivery algorithm configured to provide an electrical signal of stimulation energy deliverable through the catheter in order to create the lesions in the region of cardiac tissue; a subsystem for use with the catheter connected to the signal generator, wherein the catheter comprises a catheter body comprising a distal portion and a proximal portion, the distal portion of the catheter body comprising a plurality of electrodes electrically isolated from one another, the proximal portion of the catheter body comprising a plurality of terminals and connectable to the signal generator in order to enable the stimulation energy to be delivered via a selected one or more of the electrodes, and the catheter further comprising a plurality of electrically conductive wires, wherein each electrically conductive wire electrically couples a different one of the electrodes to a different respective one of the terminals, wherein the subsystem comprises a network of components configured to keep a potential difference between the one or more electrodes of the catheter selected for delivering the stimulation energy and one or more other electrodes of the catheter not selected for delivering the stimulation energy below a threshold potential difference that prevents arcing between one or more pairs of the electrically conductive wires; wherein the network of components comprises a plurality of resistors; and wherein the plurality of electrodes comprises one electrode selected for delivering the stimulation energy and three electrodes not selected for delivering the stimulation energy, and wherein the plurality of resistors comprises a first resistor disposed between a delivery electrically conductive wire electrically coupled to the electrode selected for delivering the stimulation energy and a first electrically conductive wire electrically coupled to a first electrode of the three electrodes not selected for delivering the stimulation energy, a second resistor disposed between the delivery electrically conductive wire electrically coupled to the electrode selected for delivering the stimulation energy and a second electrically conductive wire electrically coupled to a second electrode of the three electrodes not selected for delivering the stimulation energy, and a third resistor disposed between the delivery electrically conductive wire electrically coupled to the electrode selected for delivering the stimulation energy and a third electrically conductive wire electrically coupled to a third electrode of the three electrodes not selected for delivering the stimulation energy. a third resistor disposed between the delivery conductive lead electrically coupled to the electrode selected for delivery of the stimulation energy and a third conductive lead electrically coupled to a third electrode of the three electrodes not selected for delivery of the stimulation energy.

11. The system of claim 10, wherein a total resistance network combination of the first resistor, the second resistor, and the third resistor has a maximum of 1000 to 1200 ohms.

12. A system for creating a lesion in a region of cardiac tissue of a patient, comprising: a catheter; a signal generator connected to the catheter, wherein the signal generator includes at least one energy delivery algorithm configured to provide an electrical signal of stimulation energy deliverable through the catheter in order to create the lesion in the region of cardiac tissue; a subsystem for use with the catheter connected to the signal generator, wherein the catheter includes a catheter body including a distal portion and a proximal portion, the distal portion of the catheter body including a plurality of electrodes electrically isolated from one another, the proximal portion of the catheter body including a plurality of terminals and connectable to the signal generator in order to enable delivery of the stimulation energy via selected one or more of the electrodes, and the catheter further including a plurality of conductive leads, wherein each conductive lead electrically couples a different one of the electrodes to a different respective one of the terminals, wherein the subsystem includes a network of components configured to maintain a potential difference between the one or more electrodes of the catheter selected for delivery of the stimulation energy and one or more other electrodes of the catheter not selected for delivery of the stimulation energy below a threshold potential difference that prevents arcing between one or more pairs of the plurality of conductive leads; and an interface connector including a first port for electrically connecting the catheter, wherein the first port includes separate electrical terminals corresponding to each of the plurality of electrodes, a second port for electrically connecting the signal generator to one or more of the plurality of electrodes for delivery of pulsed electric field energy thereto, a third port for electrically connecting an external device to one or more of the plurality of electrodes for transmission of low voltage energy therebetween, and a switching system including a first path of at least one lead connecting the first port with the second port and a second path of at least one lead connecting the first port with the third port, wherein the switching system switches energy transmission between the first path and the second path.

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