Treatment of cardiac tissue with pulsed electric fields

Abstract

To provide a device, system and method for treating a heart state, in particular the occurrence of arrhythmias.SOLUTION: A device, system, and method deliver therapeutic energy to portions of a heart to provide tissue modification such as to entrances to pulmonary veins in a treatment of atrial fibrillation. In general, a tissue modification system includes a specialized catheter, a high voltage waveform generator, and at least one distinct energy delivery algorithm. Other embodiments include conventional ablation catheters and system components to enable use with a high voltage waveform generator. Example catheter designs include a variety of delivery types including focus delivery, a "one-shot" delivery, and various possible combinations. In some embodiment, the energy is delivered in a monopolar fashion. However, it may be appreciated that a variety of other embodiments are also provided.SELECTED DRAWING: Figure 34

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to and benefit of U.S. patent application Ser. No. 62 / 949,633, filed December 18, 2019, entitled "Treatment of Cardiac Tissue with Pulsed Electric Fields," U.S. patent application Ser. No. 63 / 000,275, filed March 26, 2020, entitled "Treatment of Cardiac Tissue with Pulsed Electric Fields," and U.S. patent application Ser. No. 63 / 083,644, filed September 25, 2020, entitled "Interface Connector for Use in Pulsed Electric Field Procedures."

[0002] The disclosures of the aforementioned applications are incorporated herein by reference in their entirety for all purposes. [Background technology]

[0003] Therapeutic energy can be applied to the heart and vasculature for the treatment of various conditions, including atherosclerosis (especially the prevention of restenosis after angioplasty) and arrhythmias such as atrial fibrillation. Atrial fibrillation is the most common sustained cardiac arrhythmia and significantly increases the risk of death for affected patients, particularly by causing stroke. In this phenomenon, the generation of erroneous electrical impulses causes the heart to deviate from normal sinus rhythm. Atrial fibrillation is thought to initiate in the myocardial sleeve of the pulmonary veins (PVs), due to the automaticity of cells within the myocardial tissue of the PVs. Pacemaker activity from these cells is thought to result in the formation of ectopic beats that initiate atrial fibrillation. PVs are also thought to be important in maintaining atrial fibrillation, as the chaotic structure and electrophysiological properties of these vessels provide an environment in which atrial fibrillation can perpetuate. Therefore, the destruction or removal of these abnormal pacemaker cells within the myocardial sleeve of the PVs is the goal, and atrial fibrillation is often treated by delivering therapeutic energy to the pulmonary veins. However, due to reports of PV stenosis, the approach has traditionally been modified to target the PV anterior wall to achieve conduction block between the PV and the left atrium. In addition to the pulmonary veins, the PV anterior wall includes the roof and posterior wall of the left atrium, and in the case of right pulmonary vein anterior wall, part of the atrial septum. In some instances, this technique offers a higher success rate and lower complication rate compared to isolation of the pulmonary vein ostium.

[0004] Thermal ablation therapy, specifically radiofrequency (RF) ablation, is currently the "gold standard" for treating symptomatic atrial fibrillation through focal tissue necrosis. RF ablation is typically used to create a ring of ablation lesions around the outside of the ostium of each of the four pulmonary veins. RF current induces tissue desiccation by creating a localized thermal zone, resulting in discrete coagulation necrosis. The necrotic tissue acts as a conduction block, thereby electrically isolating the vein.

[0005] Despite improvements in reestablishing sinus rhythm using available methods, both success rates and safety remain limited. RF ablation continues to present multiple limitations, including long procedure times for performing pulmonary vein isolation with RF focal catheters, potential gaps in ablation patterns with point-by-point ablation techniques with conventional RF catheters, and difficulties in creating and confirming transmural ablation lesions due to high temperatures, which can lead to thrombosis or embolism during ablation; thermal damage to collateral extracardiac structures; pulmonary vein stenosis, phrenic transcatheter injury, esophageal injury, atrioesophageal fistula, peresophageal vagus nerve injury, perforation, thromboembolic events, vascular complications, and acute coronary artery occlusion, to name a few. These limitations are primarily due to the ongoing battle clinicians face in balancing effective therapeutic doses with inadequate energy delivery to extracardiac tissues.

[0006] Therefore, while maintaining the technology in clinical practice, safer and more versatile methods of removing abnormal tissue are being used, including irreversible electroporation (IRE), a non-thermal therapy based on the irreversible permeability of cell membranes caused by specific, brief pulses of high-voltage energy. IRE is tissue-specific, induces apoptosis rather than necrosis, and has been shown to be safer for structures adjacent to the myocardium. However, to date, the success of these IRE methodologies has been uneven. In some instances, IRE energy delivery has resulted in incomplete block of the abnormal electrical rhythm. This may be due to various factors, such as irregular treatment around the pulmonary veins, lack of transmural delivery of energy, or other defects in energy delivery. In either case, atrial fibrillation is either not adequately treated or atrial fibrillation recurs later. Therefore, improved atrial fibrillation treatment is desirable. Such treatment should be safe, effective, and lead to reduced complications. At least some of these objectives may be achieved by the systems, devices, and methods described herein. Summary of the Invention

[0007] Described herein are embodiments of devices, systems, and methods for treating target tissue, particularly cardiac tissue. The invention also relates to the following numbered paragraphs:

[0008] 1. A system for treating cardiac tissue of a patient, comprising: a treatment catheter having a delivery electrode; a generator electrically coupleable to the treatment catheter, the generator including at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through the delivery electrodes; The system, wherein the treatment catheter and generator together are configured to monopolarly deliver pulsed electric field energy through cardiac tissue to a remote return electrode.

[0009] 2. The system of claim 1, wherein the delivery electrode is cylindrical in shape and has a distal surface configured to be positioned against cardiac tissue.

[0010] 3. The system of claim 2, wherein the distal face has a single continuous surface.

[0011] 4. A system according to any one of the preceding claims, wherein the delivery electrode comprises a distal face having a contact surface configured to be positioned against cardiac tissue.

[0012] 5. The system of claim 4, wherein the contact surface has a circular shape with a diameter of 2 to 3 mm.

[0013] 6. The system of claim 4, wherein the contact surface has a surface area of ​​3 to 8 mm2.

[0014] 7. The system of claim 4, wherein the contact surface is configured to have a current density of 2 amps per square millimeter while delivering 15 joules of pulsed electric field energy.

[0015] 8. A system according to any one of the preceding claims, wherein the electrical signal of pulsed electric field energy has a voltage of at least 2000V.

[0016] 9. A system according to any one of the preceding claims, wherein the electrical signal comprises packets of biphasic pulses.

[0017] 10. A system according to any one of the preceding claims, wherein the generator is configured to receive a measurement of depth of cardiac tissue and to select one of the at least one energy delivery algorithm based on the depth measurement.

[0018] 11. A system according to any one of the preceding claims, wherein the generator is configured to receive a measurement of cardiac tissue depth and to select one of at least one energy delivery algorithm that provides energy that is believed to create a non-thermal lesion having a depth that exceeds the measurement of cardiac tissue depth.

[0019] 12. The system of claim 10 or 11, wherein the depth measurements are received from an imaging device.

[0020] 13. A system according to claim 10 or 11, wherein the depth measurements are received from a data input.

[0021] 14. The system of any one of the preceding claims, wherein the delivery electrodes and electrical signal are configured such that pulsed electric field energy delivered through the delivery electrodes to the cardiac tissue creates a non-thermal lesion in the cardiac tissue that is at least 4 mm deep, such that up to 30 Joules of pulsed electric field energy is delivered through the delivery electrodes and electrical signal.

[0022] 15. The system of any one of the preceding claims, wherein the delivery electrodes and electrical signal are configured such that pulsed electric field energy delivered through the delivery electrodes to the cardiac tissue creates a non-thermal lesion in the cardiac tissue that is at least 7 mm deep, such that up to 400 Joules of pulsed electric field energy is delivered through the delivery electrodes and electrical signal.

[0023] 16. The system of any one of the preceding claims, wherein the cardiac tissue is proximate to an extracardiac structure, and the delivery electrode and electrical signal are configured such that pulsed electric field energy delivered through the cardiac tissue to the remote electrode assists in preventing thermal damage to the extracardiac structure.

[0024] 17. The system of any one of the preceding claims, wherein the cardiac tissue includes a triceps caval isthmus, and wherein the electrical signal is configured such that pulsed electric field energy delivered through the delivery electrode to the triceps caval isthmus creates a non-thermal lesion at a depth of at least 10 mm.

[0025] 18. The catheter of any one of the preceding claims, wherein the cardiac tissue includes a ventricle and the electrical signal is configured such that pulsed electric field energy delivered to the ventricle through the delivery electrode creates a non-thermal lesion at a depth of at least 7 mm through the delivery electrode and the electrical signal.

[0026] 19. The catheter of any one of the preceding claims, wherein the cardiac tissue includes an anterior wall of the heart, and wherein the electrical signal is configured such that pulsed electric field energy delivered to the anterior wall through the delivery electrode creates a non-thermal lesion at least 5 mm deep.

[0027] 20. A system according to any one of the preceding claims, further comprising a cardiac monitor that measures the patient's heart rate in beats per minute, and wherein the generator is configured to modify energy delivery based on at least one measurement of the heart rate in beats per minute.

[0028] 21. The system of claim 20, wherein the generator is configured to cease energy delivery when at least one measurement of the heart rate per minute is below a predetermined threshold.

[0029] 22. The system of claim 21, wherein the predetermined threshold is 30 beats per minute.

[0030] 23. The system of any one of claims 20-22, wherein the generator is configured to provide energy delivery less frequently when at least one measurement of the heart rate is equal to or greater than a predetermined threshold.

[0031] 24. The system of claim 23, wherein the less frequent frequency includes every other heartbeat.

[0032] 25. The system of claim 23 or 24, wherein the predetermined threshold is 120 beats per minute.

[0033] 26. A system according to any one of the preceding claims, wherein the generator further comprises a temperature sensor configured to modify energy delivery based on at least one measurement from the temperature sensor.

[0034] 27. The system of claim 26, wherein modifying the energy delivery includes providing less frequent energy delivery when at least one measurement from the temperature sensor is at or above a predetermined threshold.

[0035] 28. The system of claim 27, wherein the less frequent frequency includes every other heartbeat.

[0036] 29. The system of claim 27 or 28, wherein the predetermined threshold is 65°C.

[0037] 30. The system of any one of claims 26-29, wherein at least one measurement comprises a series of measurements indicative of a rapid increase in temperature.

[0038] 31. The system of claim 30, wherein the rapid increase in temperature comprises a change of 3 to 5 degrees Celsius across a heartbeat.

[0039] 32. The system of any one of claims 26-31, wherein the treatment catheter further comprises at least one irrigation port, and wherein the system further comprises an irrigation pump, the irrigation pump configured to vary delivery of irrigation fluid through the irrigation pump based on at least one measurement from the temperature sensor.

[0040] 33. The system of any one of the preceding claims, further comprising a contact sensor, wherein the generator is configured to modify at least one of the at least one energy delivery algorithm based on at least one measurement from the contact sensor.

[0041] 34. The system of any one of the preceding claims, further comprising a contact force sensor, wherein the generator is configured to modify at least one of the at least one energy delivery algorithm based on at least one measurement from the contact force sensor.

[0042] 35. A system for creating a lesion in a region of cardiac tissue of a patient, comprising: a treatment catheter having a delivery electrode; a generator electrically coupleable to the treatment catheter, the generator including at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through a delivery electrode to create a lesion in cardiac tissue, the lesion being deep enough to block electrical signals through a region of cardiac tissue.

[0043] 36. The system of claim 35, wherein the electrical signal comprises a series of biphasic pulses.

[0044] 37. The system of claim 36, wherein the series of biphasic pulses is delivered in multiple packets.

[0045] 38. The system of claim 37, wherein each packet of the plurality of packets includes between 30 and 45 biphasic pulses.

[0046] 39. The system of claim 37 or 38, wherein multiple packets are delivered in multiple bundles, each bundle being delivered during a predetermined portion of each heartbeat.

[0047] 40. The system of claim 39, wherein the predetermined portion includes a T wave.

[0048] 41. The system of claim 39 or 40, wherein each bundle contains 1 to 3 packets.

[0049] 42. The system of claim 41, wherein 10 to 30 packets are delivered to create a lesion.

[0050] 43. The system of any one of claims 35-42, wherein the delivery electrode is cylindrical in shape and has a distal surface configured to be positioned against a region of cardiac tissue.

[0051] 44. The system of claim 43, wherein the distal surface has a single continuous surface.

[0052] 45. The system of any one of claims 35-44, wherein the delivery electrode comprises a distal face having a contact surface configured to be positioned against a cardiac tissue region.

[0053] 46. ​​The system of any one of claims 35-45, wherein the treatment catheter and generator together are configured to deliver pulsed electric field energy monopolarly through a region of cardiac tissue to a remote return electrode.

[0054] 47. The system of any one of claims 35-46, wherein the region of cardiac tissue includes a pulmonary vein and has a depth sufficient to block conduction between the pulmonary vein and the remainder of the heart.

[0055] 48. A catheter for treating a region of cardiac tissue, comprising: a shaft having a longitudinal axis; a delivery electrode having a conductive rim extending about a longitudinal axis, the continuous rim having a closed shape configured to mate with the opening of a pulmonary vein to create a continuous lesion around the opening of the pulmonary vein.

[0056] 49. The catheter of claim 48, wherein the delivery electrode includes one or more loops, a portion of the loop forming a conductive rim.

[0057] 50. The catheter of claim 49, wherein one or more loops are constructed of conductive wire.

[0058] 51. The catheter of any one of claims 48-50, wherein the continuous limb forms a closed shape having an adjustable diameter.

[0059] 52. The catheter of claim 51, wherein the adjustable diameter is adjustable by pressing the continuous rim against a region of cardiac tissue, causing one or more loops to move relative to one another.

[0060] 53. The catheter of claim 52, wherein the movement relative to one another includes a change in overlap of at least two portions of the one or more loops.

[0061] 54. The catheter of claim 48, wherein the delivery electrode has a funnel shape extending outward from the longitudinal axis of the shaft, with a conductive rim extending around the mouth of the funnel shape.

[0062] 55. The catheter of claim 54, wherein the continuous limb forms a closed shape having an adjustable thickness.

[0063] 56. The catheter of claim 55, wherein the adjustable thickness is adjustable by pressing the funnel-shaped mouth against an area of ​​cardiac tissue.

[0064] 57. The catheter of claim 56, wherein the delivery electrode is comprised of multiple conductive wires, and at least some of the multiple conductive wires are drawn together by pressing the funnel-shaped mouth against a region of cardiac tissue.

[0065] 58. The catheter of any one of claims 48-57, wherein the delivery electrode comprises at least two independently energizable electrodes.

[0066] 59. The catheter of any of claims 48-58, wherein the delivery electrode is configured to deliver energy monopolarly through cardiac tissue to a remote return electrode.

[0067] 60. A subsystem for use with a catheter configured to be connected to a signal generator, the catheter comprising a catheter body including a distal portion and a proximal portion, the distal portion of the catheter body comprising a plurality of electrodes electrically insulated from one another, the proximal portion of the catheter body comprising a plurality of terminals and configured to be connected to the signal generator thereby allowing stimulation energy to be delivered through selected one or more of the electrodes, the catheter also comprising a plurality of conductive wires each electrically coupling a different one of the electrodes to a respective different one of the terminals, the subsystem comprising: A subsystem comprising a network of components configured to maintain a potential difference between one or more of the electrodes of the catheter selected to deliver stimulation energy and one or more other electrodes of the catheter not selected to deliver stimulation energy below a threshold potential difference that prevents arcing between one or more pairs of conductive wires.

[0068] 61. The subsystem of claim 60, wherein the component network includes a plurality of resistors.

[0069] 62. The subsystem of claim 61, wherein each of the plurality of resistors is disposed between a conductive line electrically coupled to an electrode selected for delivering stimulation energy and a conductive line electrically coupled to an electrode not selected for delivering stimulation energy.

[0070] 63. A method for treating a stimulating electrode comprising: a plurality of electrodes including one electrode selected to deliver stimulation energy and three electrodes not selected to deliver stimulation energy; and a plurality of resistors; a first resistor disposed between a delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a first conductive line electrically coupled to a first of the three electrodes not selected to deliver stimulation energy; a second resistor disposed between the delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a second conductive line electrically coupled to a second of the three electrodes not selected to deliver stimulation energy; 63. The subsystem of claim 62, comprising: a third resistor disposed between a delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a third conductive line electrically coupled to a third of the three electrodes not selected to deliver stimulation energy.

[0071] 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.

[0072] 65. The subsystem of claim 63 or 64, wherein the total resistive network combination of the first resistor, the second resistor, and the third resistor is a maximum of 1000 to 1200 ohms.

[0073] 66. The subsystem of claim 60, wherein the component network includes at least one resistor, inductor, or diode.

[0074] 67. The subsystem of claim 66, wherein at least one value of at least one resistor, inductor, or diode is selectable.

[0075] 68. The subsystem of claim 67, further comprising an algorithm that determines at least one value based on information provided by a user.

[0076] 69. The subsystem of claim 68, wherein the algorithm includes a three-dimensional mathematical model of the current distribution from the catheter.

[0077] 70. The subsystem of claim 68 or 69, wherein the information provided by the user includes voltage, frequency, or energy amplitude.

[0078] 71. The subsystem of any one of claims 68-70, wherein the information provided by the user includes the number of electrodes, the dimensions of the electrodes, the distance between the electrodes, the brand of catheter, the model of catheter, and / or the type of energy for which the catheter is designed.

[0079] 72. The subsystem of any one of claims 68-71, wherein the information provided by the user includes target tissue type, target cell type, conductance, impedance, temperature, irrigation status, and / or anatomical location.

[0080] 73. The subsystem of any one of claims 60 to 72, wherein the threshold potential difference is less than or equal to 1000 to 1500 volts.

[0081] 74. The subsystem of any one of claims 60-73, wherein the total current flowing through the component network is below a predetermined threshold current level.

[0082] 75. The subsystem of claim 74, wherein the predetermined threshold current level is 40 amps.

[0083] 76. The subsystem of any one of claims 60-75, wherein the subsystem is configured to be connected between the signal generator and the catheter.

[0084] 77. A subsystem according to any one of claims 60 to 75, wherein the subsystem is part of a signal generator.

[0085] 78. The subsystem of any one of claims 60 to 75, wherein the subsystem is part of a catheter.

[0086] 79. The subsystem of any one of claims 60-78, wherein the catheter is configured to avoid arcing between one or more pairs of conductive wires when receiving stimulation energy having a voltage up to a predetermined voltage level, and wherein the energy delivered by the signal generator comprises energy above the predetermined voltage level at which the subsystem prevents arcing between one or more pairs of conductive wires.

[0087] 80. The subsystem of claim 79, wherein the predetermined voltage level comprises 1000 to 1500 volts.

[0088] 81. The subsystem of any one of claims 60-80, wherein the catheter comprises a radiofrequency ablation catheter.

[0089] 82. The subsystem of claim 81, wherein the stimulation energy comprises pulsed electric field energy.

[0090] 83. The subsystem of claim 81 or 82, wherein the stimulation energy has a voltage of at least 2000V.

[0091] 84. A system for adapting a catheter having a plurality of electrodes electrically isolated from one another, at least one of the plurality of electrodes being selectable for delivery of stimulation energy, the catheter comprising a plurality of conductive wires each electrically coupled to a different one of the electrodes, the system comprising: A system comprising a component network configured to increase a current threshold for arcing between one or more pairs of conductive lines.

[0092] 85. The system of claim 84, wherein the component network comprises a plurality of resistors.

[0093] 86. The system of claim 85, wherein each of the plurality of resistors is disposed between a conductive line electrically coupled to an electrode selected to deliver stimulation energy and a conductive line electrically coupled to an electrode not selected to deliver stimulation energy.

[0094] 87. The plurality of electrodes includes one electrode selected to deliver stimulation energy and three electrodes not selected to deliver stimulation energy, and the plurality of resistors are: a first resistor disposed between a delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a first conductive line electrically coupled to a first of the three electrodes not selected to deliver stimulation energy; a second resistor disposed between the delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a second conductive line electrically coupled to a second of the three electrodes not selected to deliver stimulation energy; 87. The system of claim 86, comprising: a third resistor disposed between a delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a third conductive line electrically coupled to a third of the three electrodes not selected to deliver stimulation energy.

[0095] 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.

[0096] 89. The system of claim 87 or 88, wherein the total resistive network combination of the first resistor, the second resistor, and the third resistor is a maximum of 1000 to 1200 ohms.

[0097] 90. The system of claim 84, wherein the component network includes at least one resistor, inductor, or diode.

[0098] 91. The system of claim 90, wherein at least one value of at least one resistor, inductor, or diode is selectable.

[0099] 92. The system of claim 91, further comprising an algorithm that determines at least one value based on information provided by a user.

[0100] 93. The system of claim 92, wherein the algorithm includes a three-dimensional mathematical model of the current distribution from the catheter.

[0101] 94. The system of claim 92 or 93, wherein the information provided by the user includes voltage, frequency, or energy amplitude.

[0102] 95. The system of any one of claims 92-94, wherein the information provided by the user includes the number of electrodes, the dimensions of the electrodes, the distance between the electrodes, the brand of catheter, the model of catheter, and / or the type of energy for which the catheter is designed.

[0103] 96. The system of any one of claims 92-95, wherein the information provided by the user includes target tissue type, target cell type, conductance, impedance, temperature, irrigation status, and / or anatomical location.

[0104] 97. The system of any one of claims 84-96, wherein the arcing current threshold is 40 amperes.

[0105] 98. The system of any one of claims 84-97, wherein the system is configured to be connected between a signal generator and a catheter.

[0106] 99. The system of any one of claims 84 to 97, wherein the system is part of a signal generator.

[0107] 100. The system of any one of claims 84 to 97, wherein the system is part of a catheter.

[0108] 101. The system of any one of claims 84-100, wherein the catheter comprises a radiofrequency ablation catheter.

[0109] 102. The system of any one of claims 84-100, wherein the catheter comprises a microwave ablation catheter.

[0110] 103. The system of any one of claims 84-102, wherein the stimulation energy comprises pulsed electric field energy.

[0111] 104. The system of claim 103, wherein the stimulation energy has a voltage of at least 2000V.

[0112] 105. A system for adapting a catheter that at least partially fails when receiving stimulation energy having a voltage or current above a threshold level, comprising: A system comprising: a component network coupleable to a catheter, the component network increasing a threshold level to a higher threshold level.

[0113] 106. The system of claim 105, wherein the catheter comprises a dielectric material and the at least partial failure comprises a breakdown of the dielectric material.

[0114] 107. The system of claim 105, wherein the catheter comprises conductive wires insulated by an insulating material, and wherein the system failing at least partially comprises a breakdown of the insulating material.

[0115] 108. The system of any one of claims 105-107, wherein the higher threshold level is at least 20% greater than the threshold level.

[0116] 109. The system of claim 108, wherein the higher threshold level is at least 40% greater than the threshold level.

[0117] 110. The system of any one of claims 105-109, wherein the catheter is configured to receive stimulation energy including radiofrequency or microwave energy, and the component network adapts the catheter to be capable of receiving stimulation energy including high voltage energy.

[0118] 111. The system of claim 110, wherein the high voltage energy comprises pulsed electric field energy, irreversible electroporation energy, pulsed radiofrequency ablation, or nanosecond pulsed electric field energy.

[0119] 112. The system of any one of claims 105-111, wherein the catheter at least partially fails when it receives stimulation energy having a voltage or current above a threshold level due to arcing between one or more pairs of conductive wires, and wherein the component network prevents arcing between one or more pairs of conductive wires when it receives stimulation energy having a voltage or current above a threshold level and below a higher threshold level.

[0120] 113. A system as described in any one of claims 105-112, wherein the component network maintains a potential difference between one or more pairs of conductive wires that does not exceed a potential difference threshold when the component network receives stimulation energy having a voltage or current above a threshold level and below a higher threshold level.

[0121] 114. The system of claim 113, wherein the potential difference threshold is between 1000 and 1500 volts.

[0122] 115. The system of claim 113, wherein the potential difference threshold is 1000 volts.

[0123] 116. The system of any one of claims 105-115, wherein the component network includes a resistor, an inductor, or a diode.

[0124] 117. The system of claim 116, wherein the component network includes a plurality of resistors, each of the plurality of resistors being disposed between a conductive line electrically coupled to an electrode selected for delivering stimulation energy and a conductive line electrically coupled to an electrode not selected for delivering stimulation energy.

[0125] 118. The plurality of electrodes includes one electrode selected to deliver stimulation energy and three electrodes not selected to deliver stimulation energy, and the plurality of resistors are: a first resistor disposed between a delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a first conductive line electrically coupled to a first of the three electrodes not selected to deliver stimulation energy; a second resistor disposed between the delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a second conductive line electrically coupled to a second of the three electrodes not selected to deliver stimulation energy; 118. The system of claim 117, comprising: a third resistor disposed between a delivery conductive line electrically coupled to the electrode selected to deliver stimulation energy and a third conductive line electrically coupled to a third of the three electrodes not selected to deliver stimulation energy.

[0126] 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.

[0127] 120. The system of claim 118 or 119, wherein the total resistive network combination of the first resistor, the second resistor, and the third resistor is a maximum of 1000 to 1200 ohms.

[0128] 121. The system of claim 116, wherein at least one value of at least one resistor, inductor, or diode is selectable.

[0129] 122. The system of claim 121, further comprising an algorithm that determines at least one value based on information provided by a user.

[0130] 123. The system of claim 122, wherein the algorithm includes a three-dimensional mathematical model of the current distribution from the catheter.

[0131] 124. The system of claim 122 or 123, wherein the information provided by the user includes voltage, frequency, or energy amplitude.

[0132] 125. The system of any one of claims 122-124, wherein the information provided by the user includes the number of electrodes, the dimensions of the electrodes, the distance between the electrodes, the brand of catheter, the model of catheter, and / or the type of energy for which the type of catheter is designed.

[0133] 126. The system of any one of claims 122-125, wherein the information provided by the user includes target tissue type, target cell type, conductance, impedance, temperature, irrigation status, and / or anatomical location.

[0134] 127. The system of any one of claims 105-126, further comprising a high voltage generator that generates stimulation energy having a voltage or current above a threshold level.

[0135] 128. The system of claim 127, wherein the component network is disposed within the generator.

[0136] 129. The system of any one of claims 105-128, wherein the component network comprises one or more potentiometers, rheostats, or variable resistors.

[0137] 130. The system of any one of claims 105-129, wherein the component network comprises one or more capacitors, inductors, or diodes.

[0138] 131. The system of any one of claims 105-130, wherein the catheter comprises a radiofrequency ablation catheter or a microwave catheter.

[0139] 132. The system of any one of claims 105-131, wherein the stimulation energy comprises pulsed electric field energy.

[0140] 133. The system of claim 132, wherein the stimulation energy has a voltage of at least 2000V.

[0141] 134. A system comprising: a catheter having a delivery electrode, the catheter configured to deliver thermal ablation energy; and a generator electrically coupleable to the treatment catheter, the generator including at least one energy delivery algorithm configured to provide an electrical signal of non-thermal high-voltage energy deliverable through the delivery electrode.

[0142] 135. The system of claim 134, wherein the thermal ablation energy comprises radiofrequency ablation energy.

[0143] 136. The system of claim 134, wherein the thermal ablation energy comprises microwave ablation frequencies.

[0144] 137. The system of any one of claims 134-136, wherein the high voltage energy comprises pulsed electric field energy.

[0145] 138. The system of any one of claims 134-137, wherein the high voltage energy comprises irreversible electroporation energy, pulsed radiofrequency ablation, or nanosecond pulsed electric field energy.

[0146] 139. The system of any one of claims 134-138, wherein the high voltage energy has a voltage of at least 2000V.

[0147] 140. The system of any one of claims 134-139, wherein the high-voltage energy comprises an electrical signal having packets of biphasic pulses.

[0148] 141. The system of any one of claims 134-140, wherein the treatment catheter and generator together are configured to monopolarly deliver pulsed electric field energy through tissue to a remote return electrode.

[0149] 142. The system of any one of claims 134-141, wherein the generator is configured to receive a tissue depth measurement and select one of at least one energy delivery algorithm that provides energy that is expected to create a non-thermal lesion having a depth that exceeds the tissue depth measurement.

[0150] 143. The system of claim 142, wherein the tissue comprises cardiac tissue.

[0151] 144. The system of any one of claims 134-143, further comprising a component network coupleable with the catheter, the component network configured to increase a current threshold for arcing between one or more pairs of conductive wires within the catheter.

[0152] 145. The system of claim 144, wherein the component network includes a plurality of resistors.

[0153] 146. The system of claim 145, wherein the catheter further comprises at least one electrode not selected for delivering stimulation energy, and wherein each of the plurality of resistors is disposed between a conductive line electrically coupled to the delivery electrode and a conductive line electrically coupled to one of the at least one electrode not selected for delivering stimulation energy.

[0154] 147. The system of any one of claims 134-146, further comprising an electroanatomical mapping system electrically coupleable to the treatment catheter.

[0155] 148. The system of claim 147, further comprising an interface connector electrically coupling the catheter to both the generator and the electroanatomical mapping system, the interface connector preventing the delivery electrodes from being in electrical communication with both the generator and the electroanatomical mapping system simultaneously.

[0156] 149. The system of claim 148, wherein the interface connector comprises a switching system including a first pathway of at least one conductive line between the delivery electrode and the generator and a second pathway of at least one conductive line between the delivery electrode and the electroanatomical mapping system, the switching system toggling energy transmission between the first pathway and the second pathway.

[0157] 150. The system of claim 149, wherein the switching system toggles by selectively opening and closing one or more switches.

[0158] 151. The system of any one of claims 134-150, further comprising a module electrically coupleable to the treatment catheter.

[0159] 152. The system of claim 151, wherein the catheter includes a thermocouple and the module includes components for temperature monitoring.

[0160] 153. The system of claim 151 or 152, wherein the catheter includes a contact sensor and the module comprises components for monitoring contact.

[0161] 154. The system of any one of claims 151-153, wherein the catheter includes a contact force sensor and the module comprises components for monitoring the contact force.

[0162] 155. The system of any one of claims 134-154, further comprising an external cardiac monitor electrically coupleable to the generator.

[0163] 156. The system of any one of claims 134-155, further comprising an external return electrode electrically coupleable to the generator.

[0164] 157. A system for treating cardiac tissue of a patient, comprising: a treatment catheter having at least one contact point; a generator electrically coupleable to the treatment catheter, the generator including 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 contact; an interface connector that electrically couples the at least one contact to both the generator and the electroanatomical mapping system, the interface connector preventing the at least one contact from simultaneously electrically communicating with both the generator and the electroanatomical mapping system.

[0165] 158. The system of claim 157, wherein the interface connector comprises a switching system including a first pathway of at least one conductive line between the at least one contact and the generator and a second pathway of at least one conductive line between the at least one contact and the electroanatomical mapping system, the switching system toggling energy transmission between the first pathway and the second pathway.

[0166] 159. The system of claim 158, wherein the switching system toggles by selectively opening and closing one or more switches.

[0167] 160. The system of claim 159, wherein at least one of the one or more switches comprises a high voltage relay.

[0168] 161. The system of claim 159, wherein at least one of the one or more switches can be open while at least one of the one or more switches is closed.

[0169] 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.

[0170] 163. The system of any one of claims 157-162, wherein at least one of the at least one contact senses an input signal.

[0171] 164. The system of claim 163, wherein the input signal comprises a cardiac mapping signal or a cardiac electrogram.

[0172] 165. The system of any one of claims 157-163, wherein the at least one contact includes a plurality of contacts, and the interface connector includes a separate electrical terminal corresponding to each of the plurality of contacts.

[0173] 166. The system of any one of claims 157-165, wherein at least one contact comprises a plurality of electrodes electrically isolated from one another, at least one of the plurality of electrodes being selectable for delivery of stimulation energy.

[0174] 167. The system of claim 166, wherein the catheter comprises a plurality of conductive wires each electrically coupled to a different one of the plurality of electrodes, and wherein the interface connector further comprises a component network configured to increase a current threshold for arcing between one or more pairs of conductive wires.

[0175] 168. The system of claim 166, wherein the component network is configured to maintain a potential difference between one or more pairs of conductive lines.

[0176] 169. The system of any one of claims 157-168, wherein at least one contact includes a thermocouple electrically coupleable to an electroanatomical mapping system.

[0177] 170. The system of any one of claims 157-168, wherein at least one junction includes a thermocouple electrically coupleable to a module including a component for temperature monitoring.

[0178] 171. The system of claim 170, wherein the thermocouple is in electrical communication with the module independent of communication between the catheter and the generator or between the catheter and the electroanatomical mapping system.

[0179] 172. The system of any one of claims 157-171, wherein at least one contact includes a contact or contact force sensor electrically coupleable to an electroanatomical mapping system.

[0180] 173. The system of any one of claims 157-171, wherein at least one contact comprises a contact or force sensor electrically coupleable to a module comprising components for contact or force sensing.

[0181] 174. The system of claim 173, wherein the contact sensor or contact force sensor is in electrical communication with the module independent of communication between the catheter and the generator or between the catheter and the electroanatomical mapping system.

[0182] 175. The system of any one of claims 157-174, wherein the treatment catheter is configured to deliver pulsed electric field energy in a monopolar manner.

[0183] 176. The system of claim 175, wherein the interface connector electrically couples the generator to a return electrode configured to be positioned remotely from the treatment catheter.

[0184] 177. The system of claim 175, further comprising a return electrode configured to be positioned remotely from the treatment catheter.

[0185] 178. An interface connector, a first port for electrically connecting a catheter having at least one contact, the first port including a separate electrical terminal corresponding to each of the at least one contact; a second port for electrically connecting a generator to one or more of the at least one contact for delivering high voltage energy through the generator and the contact; a third port for electrically connecting an external device to one or more of the at least one contacts to transfer low voltage energy between the external device and the contacts; 1. An interface connector comprising: a switching system comprising: a first path of at least one conductive line connecting a first port to a second port; and a second path of at least one conductive line connecting the first port to a third port, wherein the switching system toggles energy transfer between the first path and the second path.

[0186] 179. The interface connector of claim 178, wherein the high voltage energy comprises pulsed electric field energy.

[0187] 180. The interface connector of claim 178 or 179, wherein the high voltage energy has a voltage of at least 1000 volts.

[0188] 181. The interface connector of any one of claims 178-180, wherein the high voltage energy has a voltage of at least 2000 volts.

[0189] 182. The interface connector of any one of claims 178-181, wherein the low-voltage energy has a voltage of less than 500 volts.

[0190] 183. The interface connector of any one of claims 178-182, wherein the low voltage comprises a voltage in the range of 100 to 200 volts.

[0191] 184. The interface connector of any one of claims 178-183, wherein the external device comprises an electroanatomical mapping system and the low voltage energy comprises an electrical signal for measuring impedance.

[0192] 185. The interface connector of any one of claims 178-183, wherein the external device comprises an electroanatomical mapping system and the low-voltage energy comprises an electrical signal for measuring intracardiac electrical activity.

[0193] 186. The interface connector of any one of claims 178-185, wherein the switching system toggles by selectively opening and closing one or more switches.

[0194] 187. An interface connector as claimed in any one of claims 178-186, wherein at least one of the one or more switches can be open while at least one of the one or more switches is closed.

[0195] 188. The interface connector of 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.

[0196] 189. An interface connector as described in 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 through the generator and the contact, and wherein the interface connector further comprises a passive component network disposed along the first path, the passive component network modulating the energy delivered to two or more of the at least one contact to prevent catheter failure.

[0197] 190. An interface connector as described in any one of claims 178-189, wherein the second port electrically connects a generator to two or more of the at least one contact to deliver high voltage energy through the generator and the contacts, and wherein the interface connector comprises a passive component network disposed along the first path, the passive component network increasing a current threshold for arcing between one or more pairs of conductive lines with a catheter connected to two or more of the at least one contact.

[0198] 191. The interface connector of 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 conductive line connecting the first port to the fourth port.

[0199] 192. The interface connector of claim 191, wherein the other external device comprises a module.

[0200] 193. The interface connector of any one of claims 178-192, further comprising a fifth port for electrically connecting to a return electrode, and a fourth path of at least one conductive line connecting the fifth port with a sixth port configured to connect the fifth port to a generator.

[0201] 194. A method of treating a patient, comprising: advancing a distal end of a catheter into the patient's heart, the catheter having an energy delivery element disposed along the distal end of the catheter; positioning a return electrode at a location away from the distal end of the catheter, the energy delivery body at a first location along the region of cardiac tissue; delivering pulsed electric field energy unipolarly through an energy delivery body, the pulsed electric field energy being directed through cardiac tissue at a first location to a return electrode to create a first lesion; repeatedly repositioning the energy delivery body to one or more additional locations along the region of cardiac tissue; delivering pulsed electric field energy to each of the one or more additional locations to create one or more additional lesions.

[0202] 195. The method of claim 194, wherein the first lesion and the one or more additional lesions are adjacent to one another.

[0203] 196. The method of claim 194, wherein the first lesion and the one or more additional lesions partially overlap one another.

[0204] 197. The method of any one of claims 194-196, wherein the first lesion and one or more additional lesions create a closed, contiguous lesion around a pulmonary vein of the heart.

[0205] 198. The method of claim 197, wherein pulsed electric field energy is delivered and the energy delivery body is repeatedly repositioned to create a continuous lesion having sufficient depth to block conduction between the pulmonary veins and the remainder of the heart.

[0206] 199. The method of 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.

[0207] 200. The method of any one of claims 194-196, wherein the region of cardiac tissue comprises the inner surface of a pulmonary vein.

[0208] 201. The method of any one of claims 194-200, wherein the one or more additional locations comprises 10 to 50 additional locations.

[0209] 202. The method of any one of claims 194-201, wherein the region of cardiac tissue comprises the superior vena cava, the inferior vena cava, the atrium, the atrial appendage, the ventricle, the ventricular outflow tract, the interventricular septum, the ventricular summit, an area of ​​myocardial scar, the myocardial infarction border zone, the myocardial infarction channel, the ventricular endocardium, the ventricular epicardium, the papillary muscles, or a portion of the Purkinje system.

[0210] 203. A method according to any one of claims 194 to 202, wherein the energy delivery body includes a cylindrically shaped electrode having a surface disposed at the tip of the distal end of the catheter facing distally, and positioning the energy delivery body includes positioning the surface against cardiac tissue.

[0211] 204. The method of claim 203, wherein the face has a continuous flat surface.

[0212] 205. The method of claim 203 or 204, wherein the face has a curved edge.

[0213] 206. The method of any one of claims 194-202, wherein the energy delivery body includes one or more loops arranged to form a continuous rim, and positioning the energy delivery body includes positioning the continuous rim against cardiac tissue.

[0214] 207. The method of claim 206, wherein the first lesion and the one or more additional lesions each have a hoop shape.

[0215] 208. The method of claim 207, wherein the hoop shape has a diameter of 10 to 14 mm.

[0216] 209. A method according to any one of claims 194-204, wherein positioning the energy delivery body at the first location and one or more additional locations is accomplished without the use of a guidewire.

[0217] 210. The method of any one of claims 194-209, further comprising irrigating the region of cardiac tissue.

[0218] 211. A method according to any one of claims 194 to 210, further comprising sensing contact between the energy delivery body and the region of cardiac tissue.

[0219] 212. The method of any one of claims 194-211, further comprising sensing a contact force of the energy delivery body against the region of cardiac tissue.

[0220] 213. An energy delivery body includes a single electrode having a surface configured to contact cardiac tissue, through which pulsed electric field energy is delivered to the cardiac tissue, the surface being approximately 6-8 mm 2and when pulsed electric field energy is delivered through the surface, the current is 2 to 4 A / mm 2 195. The method of claim 194, generating a current density of

[0221] 214. The energy delivery body includes one or more loops arranged to form a conductive rim, the conductive rim being approximately 8-10 mm 2 and delivers pulsed electric field energy through the conductive rim, delivering 1.5-2 A / mm 2 195. The method of claim 194, generating a current density of

[0222] 215. At least one of the one or more loops is individually energizable, and the portion of the conductive rim energized by at least one of the one or more loops is approximately 1.5 to 2.5 mm 2 and delivering pulsed electric field energy through the conductive rim portion, the pulsed electric field energy is delivered at 6 to 10 A / mm 2 215. The method of claim 214, generating a current density of

[0223] 216. A method of treating atrial fibrillation in a patient, comprising: advancing a distal end of a catheter into the patient's heart, the catheter comprising a shaft having a longitudinal axis and an energy delivery body having a conductive rim extending about the longitudinal axis; positioning a return electrode away from the distal end of the catheter; positioning at least a portion of the conductive rim relative to a region of cardiac tissue through which electrical signals associated with atrial fibrillation are transmitted; unipolarly delivering pulsed electric field energy through an energy delivery body, the pulsed electric field energy being directed through cardiac tissue to a return electrode to create a lesion that blocks conduction of an electrical signal.

[0224] 217. The method of claim 216, wherein the conductive rim has an adjustable thickness, further comprising adjusting the thickness of the conductive rim.

[0225] 218. The method of claim 217, wherein adjusting the thickness of the conductive rim includes pressing the energy delivery body against a region of cardiac tissue.

[0226] 219. The method of claim 218, wherein the energy delivery body has a funnel shape extending outward from the longitudinal axis of the shaft, the conductive rim extends around the mouth of the funnel shape, and adjusting the thickness of the conductive rim includes passing the mouth of the funnel shape relative to the region of cardiac tissue.

[0227] 220. The method of claim 219, wherein the energy delivery body includes multiple wires that form a funnel shape, and at least a portion of the multiple wires are drawn together by pressing the mouth of the funnel shape against the region of cardiac tissue.

[0228] 221. The method of claim 217, wherein the energy delivery body includes one or more loops arranged to form a conductive rim, and adjusting the thickness of the conductive rim includes adjusting an overlap of at least two portions of the one or more loops.

[0229] 222. The method of any one of claims 216-221, wherein the conductive rim has an adjustable diameter, further comprising adjusting the diameter of the conductive rim.

[0230] 223. The method of claim 222, wherein adjusting the diameter of the conductive rim includes pressing the energy delivery body against a region of cardiac tissue.

[0231] 224. The method of any one of claims 216-223, wherein the energy delivery body comprises at least two individually energizable electrodes, further comprising selecting at least one of the at least two individually energizable electrodes to deliver pulsed electric field energy.

[0232] 225. The method of claim 224, further comprising selecting at least two of the electrodes to be individually energized to deliver pulsed electric field energy in a pattern.

[0233] 226. An energy delivery body includes one or more loops forming a conductive rim, at least one of the one or more loops is individually energizable, and the portion of the conductive rim energized by at least one of the one or more loops is approximately 3-5 mm 2 and delivering pulsed electric field energy through a portion of the conductive rim, wherein the conductive rim has a surface area of ​​3 to 6 A / mm 2 226. The method of any one of claims 216 to 225, wherein a current density of

[0234] 227. A method of treating a target tissue region in a patient, comprising: positioning at least one electrode of a catheter in, on, or near a target tissue region, the catheter having a baseline energy threshold for internal isolation disruption; coupling the catheter with an energy modulator, the energy modulator configured to raise an energy threshold for internal isolation disruption of the catheter above a baseline energy threshold; A method comprising: delivering energy through an energy modulator and at least one delivery electrode at an energy level above a baseline threshold for internal isolation disruption to treat a target tissue region without internal isolation disruption.

[0235] 228. The method of claim 227, wherein the internal breakdown comprises an arc discharge.

[0236] 229. The method of claim 227 or 228, wherein the catheter is configured to deliver radiofrequency energy, and the energy comprises pulsed electric field energy.

[0237] 230. The method of claim 227 or 228, wherein the catheter is configured to deliver microwave energy, and the energy comprises pulsed electric field energy.

[0238] 231. The method of any one of claims 227-230, wherein the catheter is configured to deliver energy generated by an electrical signal having a voltage of up to 1000 volts, and the energy delivered via the energy modulator is generated by an electrical signal having a voltage of at least 2000 volts.

[0239] 232. The method of any one of claims 227-231, wherein the energy modulator includes at least one passive component.

[0240] 233. The method of claim 232, wherein the at least one passive component comprises at least one resistor, inductor, capacitor, or diode.

[0241] 234. The method of claim 232, wherein the at least one passive component comprises a plurality of resistors.

[0242] 235. The method of claim 232, wherein the at least one passive component includes at least one resistor, the method further including selecting a resistance value of the at least one resistor.

[0243] 236. The method of claim 235, wherein the catheter includes at least two electrodes, each connected to a respective conductive wire, and further comprising selecting a resistance value that maintains a voltage difference between the respective conductive wires below a predetermined threshold voltage difference that would cause arcing between the respective conductive wires.

[0244] 237. The method of claim 236, wherein the predetermined threshold voltage difference is 1500V.

[0245] 238. The method of claim 236, wherein the resistance values ​​cause the total current through the individual conductive lines to be below a predetermined threshold current level.

[0246] 239. The method of claim 238, wherein the predetermined threshold current level is 40 amps.

[0247] 240. The method of any one of claims 232-239, further comprising providing information to an energy modulator used to program the energy modulator to increase the energy threshold for internal isolation disruption of the catheter above the baseline energy threshold.

[0248] 241. The method of claim 240, wherein providing information includes providing an energy parameter.

[0249] 242. The method of claim 241, wherein the parameters of the energy include voltage, frequency, waveform shape, duration, rise pulse time, fall pulse time, and / or amplitude of the energy.

[0250] 243. The method of claim 240, wherein providing information includes providing a characteristic of the catheter.

[0251] 244. The method of claim 243, wherein the catheter characteristics include the number of electrodes, the dimensions of the electrodes, the distance between the electrodes, the brand of the catheter, the model of the catheter, the type of energy for which the catheter is designed, or any combination thereof.

[0252] 245. The method of claim 240, wherein providing information includes providing an aspect of the environment of the target tissue region.

[0253] 246. The method of claim 232, wherein the environmental aspects include cell type, conductivity, impedance, temperature, and / or blood flow.

[0254] 247. The method of any one of claims 232-246, wherein treating the target tissue region includes creating at least one lesion to treat atrial fibrillation.

[0255] 248. The method of claim 247, comprising a plurality of lesions sufficiently positioned around the entrance of a pulmonary vein in the patient's atrium so as to create a conduction block between the pulmonary vein and the atrium.

[0256] 249. The method of claim 247, wherein the at least one lesion comprises a single lesion extending sufficiently around the entrance of a pulmonary vein in an atrium of the patient's heart to create a conduction block between the pulmonary vein and the atrium.

[0257] 250. A method of treating a target tissue region in a conductive environment of a patient, comprising: inserting a distal end of a catheter shaft into a patient, the catheter including a first conductive wire extending along the shaft to a delivery electrode disposed along the distal end and a second conductive wire extending along the shaft to an additional electrode disposed along the distal end, the catheter configured such that the first and second conductive wires have a threshold for arcing between the first and second conductive wires; positioning a delivery electrode of the catheter within, on, or near the target tissue region such that the delivery electrode and the additional electrode are exposed to a conductive environment to conduct energy through the first and second conductive wires; electrically coupling the first and second conductive lines to a common energy source; delivering pulsed electric field energy from a common energy source to at least the first conductive wire to a target tissue region at an energy level above an arcing threshold while avoiding arcing between the first conductive wire and the second conductive wire.

[0258] 251. A method of forming an electric field to create a lesion in a target tissue region, comprising: positioning a plurality of electrodes of the catheter in a location such that at least some of the plurality of electrodes can create a lesion in the target tissue region, wherein energy delivered by at least some of the plurality of electrodes creates an electric field; coupling the catheter with an energy modulator, the energy modulator being programmable to determine energy provided by at least some of the plurality of electrodes; programming an energy modulator to generate a desired shape of the electric field; delivering energy via an energy modulator and at least one delivery electrode to generate an electric field of a desired shape to create a lesion in a target tissue region.

[0259] These and other embodiments are described in further detail in the following description taken in conjunction with the accompanying drawings.

[0260] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. [Brief explanation of the drawings]

[0261] In the drawings, which are not necessarily drawn to scale, like numerals may describe like components in different views. Like numerals with different letter suffixes may represent different instances of like components. The drawings illustrate generally, by way of example, and not by way of limitation, various embodiments discussed in this document.

[0262] [Figure 1] 1 illustrates an embodiment of a tissue modification system. [Figure 2A-2B] 1 illustrates an embodiment of a treatment catheter configured to deliver focal therapy. [Figure 3] 1 shows a portion of the heart illustrating the atria and cutaway of the left atrium where the treatment catheter is positioned. [Figure 4]1 illustrates repeated point-by-point application of energy around the left inferior pulmonary vein using a treatment catheter to create a circular treatment zone. [Figure 5] 1 illustrates an embodiment of a signal waveform defined by an energy delivery algorithm. [Figure 6] 1 illustrates an example waveform prescribed by an energy delivery algorithm, where the waveform has a voltage imbalance. [Figure 7] 1 illustrates further examples of waveforms with unequal voltages. [Figure 8] 1 illustrates an example of a waveform with unequal pulse widths. [Figure 9] Illustrated are examples of waveforms defined by other energy delivery algorithms where the waveform is monophasic, a special case of imbalance where there is only a positive or negative portion of the waveform. [Figure 10] 1 illustrates a further example of a waveform having a monophasic pulse. [Figure 11] 1 illustrates an example of a phase-imbalanced waveform. [Figure 12] 1 illustrates an exemplary waveform defined by another energy delivery algorithm in which the pulses are sinusoidal rather than square. [Figure 13] 1 illustrates an embodiment of a conventional ablation catheter. [Figure 14A] 1 illustrates high voltage energy delivery via a conventional ablation catheter having multiple electrodes. [Figure 14B] 14B illustrates a cross section of the shaft of FIG. 14A illustrating the insulated conductive wires corresponding to the electrodes. [Figure 15] 1 illustrates schematically a resistor positioned to direct energy through conductive lines in a predetermined manner so that the voltage difference remains below a certain threshold level. [Figures 16A-16B] 1 illustrates the increase in arcing threshold when using a resistor network as described herein. [Figures 17A-17C]1 illustrates the use of resistor networks and systems described herein to shape an electric field delivered by a catheter. [Figure 18] 1 provides a schematic diagram of a cross section of the lumen of a pulmonary vein surrounded by cardiac tissue, with an electrode shown contacting the cardiac tissue through the lumen. [Figure 19] 19 is a graph showing the relationship between energy and depth of the treatment region when energy is being delivered according to the method illustrated in FIG. 18. [Figure 20-21] Mathematical modeling illustrates the current distribution of PFE energy emitted from the delivery electrode of the catheter under different conditions. [Figure 22] 1 illustrates a graph of current density versus penetration depth for homogeneous versus heterogeneous tissue. [Figures 23A-23B] 1 illustrates the effect of contact force on lesion size, specifically lesion width and depth. [Figure 24] 1 illustrates the thermal profile of a catheter electrode. [Figure 25] 1 illustrates a therapeutic catheter with thermal sensing and irrigation. [Figure 26] 1 illustrates an example setup in which an interface connector is utilized in an embodiment of a tissue modification system. [Figure 27-28] 1 illustrates an embodiment of an interface connector. [Figure 29] 1 illustrates the result of an "AND" logic of the generator footswitch signal and the cardiac monitor R-wave trigger signal. [Figure 30] 1 illustrates an embodiment of a connector suitable for when the signal between the catheter and the EP signal amplifier has a different frequency than the PEF output. [Figure 31] 1 illustrates an embodiment of an interface connector. [Figure 32] 1 illustrates an embodiment of an interface connector having a component network. [Figure 33] 1 illustrates another embodiment of an interface connector having a component network. [Figure 34] 1 illustrates an embodiment of a tissue modification system for use in a patient. [Figure 35] 1 is an embodiment of a tissue modification system for use with a patient, in which the treatment catheter comprises a particular conventional catheter. [Figure 36] 1 illustrates an embodiment of a treatment catheter configured to deliver a "one-shot" therapy. [Figure 37A-37B] 1 illustrates an embodiment of a delivery electrode configured to deliver a "one-shot" therapy, where the delivery electrode has a cup or funnel shape. [Figure 38A-38B] Illustrates application of delivery electrodes 37A and 37B to a surface. [Figure 39] 38A and 38B illustrate an embodiment of a delivery electrode in which a portion of the multiple wires is covered with insulation. [Figure 40A] 1 provides a schematic illustration of a cross section of the lumen of a pulmonary vein surrounded by cardiac tissue, with a treatment catheter shown having delivery electrodes contacting the cardiac tissue at various locations through the lumen. [Figure 40B] 40B is a graph showing the relationship between energy and depth of the treatment region when energy is being delivered according to the method shown in FIG. 40A. [Figure 41] 1 illustrates an embodiment of a delivery electrode that includes an initial single loop that forms a bilayer rim. [Figure 42] FIG. 42 provides a side view of the delivery electrode shown in FIG. 41 . [Figures 43A-43E] 43 illustrates deployment of the delivery electrodes of FIGS. 41 and 42. FIG. [Figure 44A] 1 illustrates an embodiment of a delivery electrode having two loops that extend at least partially around a circular rim such that the rim is constructed from two layers of wire in two sections. [Figure 44B] 44B illustrates the two loops of FIG. 44A separated for visualization. [Figure 45] FIG. 45 provides a side view of the delivery electrode shown in FIG. 44. [Figure 46A] 1 illustrates an embodiment of a delivery electrode having three loops extending at least partially around a circular rim such that the rim is constructed from two layers of wire in three sections. [Figure 46B] Shown are three loops of 16A separated for visualization. [Figure 47] FIG. 46B provides a side view of the delivery electrode shown in FIG. 46A. DETAILED DESCRIPTION OF THE INVENTION

[0263] Devices, systems, and methods are provided for treating cardiac conditions, particularly arrhythmias, and more specifically, the occurrence of atrial fibrillation, atrial flutter, ventricular tachycardia, Wolff-Parkinson-White syndrome, and / or atrioventricular nodal reentrant tachycardia, to name a few. The devices, systems, and methods deliver therapeutic energy to portions of the heart to provide tissue modification, such as the entrance to pulmonary veins, in the treatment of atrial fibrillation. Specific anatomical locations of interest include the superior vena cava, inferior vena cava, right pulmonary veins, left pulmonary veins, 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 apex, areas of myocardial scar, myocardial infarction border zone, myocardial infarction channel, ventricular endocardium, ventricular epicardium, papillary muscles, and Purkinje system, to name a few. Therapies can be delivered in isolation or in a series of connected treatments. Treatment types include left atrial roofline, left atrial posterior / inferior line, posterior wall isolation, lateral mitral ischemic line, septal mitral ischemic line, left atrial appendage, right vena cava isolation (CTI), pulmonary vein isolation, superior vena cava isolation, Marshall's vein, lesion creation using complex fractionated electrocardiography (CFAE), lesion creation using focal impulse and rotor modulation (FIRM), and targeted ganglion ablation. Such tissue modification creates conduction blocks within the tissue to prevent the transmission of abnormal electrical signals. Devices, systems, and methods are typically used in electrophysiology laboratories or controlled operating rooms with fluoroscopy rooms and advanced ECG recording and monitoring capabilities. Electrophysiologists (EPs) are the primary intended users of the systems. Electrophysiologists may be supported by trained staff of nurses, technicians, and potentially other electrophysiologists. Generally, tissue modification systems include specialized catheters, a high-voltage waveform generator, and at least one distinct energy delivery algorithm. Additional accessories and equipment are available. Exemplary embodiments of specialized catheter designs are provided herein, including various delivery types, including focal delivery, "one-shot" delivery, and various possible combinations. For illustrative purposes, simplified designs are provided when describing the overall system. Such simplified designs provide monopolar focal therapy.However, it can be understood that various other embodiments are also provided.

[0264] FIG. 1 illustrates an embodiment of a tissue modification system 100 including a treatment 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 by a suitable access procedure, such as the Seldinger technique. Typically, a sheath 112 is inserted into the femoral vein FV, which serves as a conduit through which various catheters and / or tools can be advanced, including the treatment catheter 102 and the mapping catheter 104. It can be appreciated that in some embodiments, the treatment catheter 102 and the mapping catheter 104 are combined into a single device. As shown in FIG. 1, the distal ends of the catheters 102, 104 are advanced through the inferior vena cava, through the right atrium, and through a transseptal puncture into the left atrium to access the entrance to the pulmonary veins. The mapping catheter 104 is used to perform cardiac mapping, which refers to the process of identifying the temporal and spatial distribution of myocardial electrical potentials during specific cardiac rhythms. Cardiac mapping during arrhythmia aims to elucidate the mechanics of cardiac rhythm, describe the propagation of activation from initiation to completion within a region of interest, and identify sites of origin or critical conduction that can serve as targets for therapy. Once the desired treatment location is identified, a therapy catheter 102 is utilized to deliver the therapy energy.

[0265] In this embodiment, the proximal end of the treatment catheter 102 is electrically connected to a waveform generator 108, which is software-controlled with a regulated energy output that generates high-frequency, short-duration energy that is delivered to the catheter 102. It can be appreciated 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, which includes electronics for performing the mapping procedure. However, it can be appreciated that the mapping catheter 104 can instead be connected to a separate external device capable of providing a mapping procedure, such as an electroanatomical mapping (EAM) system (e.g., the CARTO® system by Biosense Webster / Johnson & Johnson, the EnSite™ system by Jude Medical / Abbott, the KODEX-EPD system by Philips, or the Rhythmia HDX™ system by Boston Scientific). Similarly, in some embodiments, a separate mapping catheter 104 is not used, and mapping functionality is incorporated into the catheter 102.

[0266] In this embodiment, the generator 108 is connected to an external cardiac monitor 110 to enable coordinated delivery of energy with cardiac signals sensed from the patient P. The generator synchronizes the energy output to the patient's cardiac rhythm. The cardiac monitor provides a trigger signal to the generator 108 upon detecting the patient's cardiac cycle R wave. This trigger signal and the generator's algorithms ensure that the energy delivery is synchronized with the patient's cardiac cycle, reducing the likelihood of arrhythmia due to the energy delivery. Typically, a footswitch allows the user to initiate and control the delivery of the energy output. The generator's user interface (UI) provides the user with both audio and visual information regarding the energy delivery and the generator's operating status.

[0267] In this embodiment, the treatment catheter 102 is designed to be monopolar, with the distal end of the catheter 108 having a delivery electrode 122 and a return electrode 106 positioned on the skin outside the body, typically on the thigh, lower back, or back. FIG. 2A illustrates an embodiment of a treatment catheter 102 configured to deliver focal therapy. In this embodiment, the catheter 102 comprises an elongated shaft 120 having a delivery electrode 122 near its distal end 124 and a handle 126 near its proximal end 128. The delivery electrode 122 is shown as a "solid-tip" electrode having a cylindrical shape with a distal face having a continuous surface. In some embodiments, the cylindrical shape is approximately 2-3 mm in diameter across its distal face and approximately 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. in length along the shaft 120. It may be understood that such electrodes are typically hollow, but are referred to as solid for visual appearance. In some embodiments, the catheter 102 has an overall length of 50-150 cm, preferably 100-125 cm, and more preferably 110-115 cm. Similarly, in some embodiments, it has an outer diameter of 7 Fr, 3-15 Fr, preferably 4-12 Fr, and more preferably 7-8.5 Fr. In some embodiments, the shaft 120 has a deflectable end portion 121, which may optionally have a length of 50-105 mm to provide a curve with a diameter ranging from approximately 15-55 mm. Deflection can be achieved by various mechanisms, including a pull wire extending to the handle 126. The handle 126 is thus used to operate the catheter 102, particularly for steering the distal end 124 during delivery and treatment. Energy is provided to the catheter 102, and thus the delivery electrode 122, via a cable 130 connectable to the generator 108.

[0268] The pulsed electric field (PEF) is provided by the generator 108 and delivered to the tissue via delivery electrodes 122 positioned on or near the target tissue region. It will be appreciated that in some embodiments, the delivery electrodes 122 are positioned in contact with a conductive material that is also in contact with the target tissue. Such solutions may include isotonic or hypertonic solutions. These solutions may further include adjuvant materials, such as chemotherapy or calcium, to further enhance the therapeutic effect on both the focal treatment and potential local infiltration areas of the target tissue type. High-voltage, brief, biphasic electrical pulses are then delivered through the electrodes 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 defines a signal having a waveform that includes a series of energy packets, each of which includes a series of high-voltage pulses. In such embodiments, the algorithm 152 specifies parameters of the signal, such as the energy amplitude (e.g., voltage) and duration of the applied energy, consisting of the number of packets, the number of pulses within the packet, and the fundamental frequency of the pulse sequence, to name a few. Additional parameters may include the switching time between polarities of the biphasic pulse, the dead time between biphasic cycles, and the pause time between packets, which will be described in more detail in later sections. There may be a fixed pause period between packets, or the packets may be gated to the cardiac cycle and therefore variable depending on the patient's heart rate. There may be an intentionally varying pause period algorithm, or no pause period may be applied between packets. Feedback loops based on sensor information, automatic shut-off specifications, etc. may be included.

[0269] It can be appreciated that in various embodiments, the treatment catheter 102 includes various specialized features. For example, in some embodiments, the catheter 102 includes a mechanism for measuring in real time the contact force applied by the catheter tip to the patient's heart wall during the procedure. In some embodiments, this mechanism is included in the shaft 120 and includes a three-axis optical force sensor that utilizes white light interferometry. By monitoring and modifying the applied force throughout the procedure, the user can better control the catheter 102 to create more consistent and effective lesions.

[0270] In some embodiments, catheter 102 includes one or more additional electrodes 125 (e.g., ring electrodes) positioned along shaft 120 proximal to delivery electrode 122, as illustrated in FIG. 2B. In some embodiments, some or all of the additional electrodes can be used for stimulation and recording (for electrophysiological mapping), so that a separate cardiac mapping catheter is not required when catheter 102 is used for other purposes, such as creating or sensing lesions.

[0271] 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 connects to one or more ports along the distal end of the catheter 102 for injection of isotonic saline solution for irrigation or for removal of microbubbles, for example.

[0272] In some embodiments, the catheter 102 includes one or more sensors that can be used to determine temperature, impedance, resistance, capacitance, conductivity, permittivity, and / or conductance, to name a few. In some embodiments, one or more electrodes function as the one or more sensors. In other embodiments, the one or more sensors are separate from the electrodes. Sensor data can be used to plan therapy, monitor therapy, and / or provide direct feedback via the processor 154, which can modify the energy delivery algorithm 152. For example, impedance measurements can be used to determine the initial dosage to be applied, as well as whether further therapy is needed.

[0273] 1 , in this embodiment, the 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 that generates and stores the energy to be delivered. In some embodiments, one or more capacitors are used for energy storage / delivery, although any other suitable energy storage elements may be used. Additionally, one or more communication ports are included.

[0274] In some embodiments, the 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 pulsed energy output to be synchronized to the patient's cardiac rhythm. The generator draws alternating current (AC) mains and powers multiple direct current (DC) power supplies. The generator's controller can cause the DC power supplies to charge a high-energy capacitor storage bank before energy delivery begins. At the start of therapeutic energy delivery, the generator's controller, high-energy storage bank, and biphasic pulse amplifier operate simultaneously to generate a high-voltage, intermediate-frequency output.

[0275] It will be appreciated that numerous generator electrical architectures can be used to implement energy delivery algorithms. In particular, some embodiments use advanced switching systems that can direct pulsed electric field circuits to energy delivery electrodes separately from the same energy storage and high-voltage delivery systems. Furthermore, generators used in advanced energy delivery algorithms that employ rapidly changing pulse parameters (e.g., voltage, frequency, etc.) or multiple energy delivery electrodes can utilize modular energy storage and / or high-voltage systems to facilitate highly customizable waveforms and geographic pulse delivery paradigms. Furthermore, it will be further appreciated that the electrical architectures described herein above are examples only, and that systems that deliver pulsed electric fields may or may not include additional switching amplifier components.

[0276] The user interface 150 may include a touch screen and / or more traditional buttons that allow the operator to enter patient data, select a treatment algorithm (i.e., the energy delivery algorithm 152), initiate energy delivery, view records stored in the storage / retrieval unit 156, and / or communicate with the generator 108.

[0277] In some embodiments, the user interface 150 is configured to receive operator-defined input. The operator-defined input can include energy delivery duration or one or more other timing aspects of the energy delivery pulse, power, and / or mode of operation, or a combination thereof. Example modes of operation can include system initiation and self-test, operator input, algorithm selection, pre-treatment system status and feedback, energy delivery, post-energy delivery display or feedback, treatment data review and / or download, software update, or a combination thereof.

[0278] As mentioned above, in some embodiments, the system 100 also includes a mechanism for acquiring an electrocardiogram (ECG), such as an external cardiac monitor 110, in situations where cardiac synchronization is desired. Examples of cardiac monitors are available from AccuSync Medical Research Corporation and Ivy Biomedical Systems, Inc. In some embodiments, the external cardiac monitor 110 is operably connected to the generator 108. The cardiac monitor 110 can be used to continuously acquire ECG signals. External electrodes 172 can be applied to the patient P to acquire the ECG. The generator 108 analyzes one or more cardiac cycles to identify the beginning of a period when it is safe to apply energy to the patient P, thus providing the ability to synchronize energy delivery with the cardiac cycle. In some embodiments, this period is within milliseconds of the R wave (of the ECG QRS complex) to avoid induction of arrhythmias, which can occur if the energy pulse is delivered at the T wave. It can be understood that such cardiac synchronization is typically utilized when using unipolar energy delivery, but may also be utilized as part of other energy delivery methods.

[0279] In some embodiments, processor 154, among other things, changes and / or switches energy delivery algorithms, monitors energy delivery and any sensor data, and responds to the monitored data via a feedback loop. In some embodiments, processor 154 is configured to execute one or more algorithms for implementing a feedback control loop based on one or more measured system parameters (e.g., current), one or more measured tissue parameters (e.g., impedance), and / or a combination thereof.

[0280] The data storage / retrieval unit 156 stores data related to the treatment being delivered, which can be downloaded as needed by connecting a device (e.g., a laptop or thumb drive) to the communications port. In some embodiments, the device has local software used to direct the download of information, e.g., stored in the data storage / retrieval unit 156 and executable by the processor 154. In some embodiments, the user interface 150 allows an operator to select data download to devices and / or systems, such as, but not limited to, computer devices, tablets, mobile devices, servers, workstations, cloud computing appliances / systems, etc. The communications port, which can allow for wired and / or wireless connections, not only allows for the download of data as just described, but also allows for the upload of data, such as uploading custom algorithms or providing software updates.

[0281] As described herein, the various energy delivery algorithms 152 can be programmable or pre-programmed into the generator 108, such as stored in a memory or data storage / retrieval unit 156. Alternatively, the energy delivery algorithms can be added to the data storage / retrieval unit to be executed by the processor 154. Each of the algorithms 152 can be executed by the processor 154.

[0282] It may be appreciated that in some embodiments, the system 100 may include automatic therapy delivery algorithms that can dynamically respond and adjust and / or terminate therapy depending on inputs such as temperature, impedance at various voltages or AC frequencies, treatment duration or other timing aspects of the energy delivery pulse, therapy power and / or system status.

[0283] As mentioned above, in some embodiments, the cardiac monitor provides a trigger signal to the generator 108 upon detecting an R wave of the patient's cardiac cycle. This trigger signal and the generator's algorithm ensure that energy delivery is synchronized with the patient's cardiac cycle, reducing the likelihood of arrhythmia due to energy delivery. This trigger is within a few milliseconds of the peak of the R wave (of the ECG QRS complex), avoiding the induction of arrhythmias that can occur if the energy pulse is delivered at the T wave and ensuring that energy delivery occurs at a consistent phase of cardiac contraction. It will be appreciated that such cardiac synchronization is typically utilized when using unipolar energy delivery, but may also be utilized as part of other energy delivery methods.

[0284] In this embodiment, the generator 108 is connected to an external cardiac monitor 110 to allow coordinated delivery of energy with cardiac signals sensed from the patient P.

[0285] In some embodiments, the generator 180 receives feedback from the cardiac monitor 110 and responds based on the received information. In some embodiments, the generator 180 receives information about the patient's heart rate and stops delivering energy or modifies energy delivery, such as by selecting a different energy delivery algorithm 152. In some embodiments, the generator 180 stops delivering energy when the heart rate reaches or falls below a threshold, such as 30 beats per minute (bpm) or 20 bpm. Optionally, the generator can provide an indicator, such as a visual or audible indicator, when the heart rate reaches or falls below a lower threshold, e.g., a flashing yellow light when the heart rate reaches 30 bpm and a solid red light when the heart rate reaches 20 bpm. Such a safety measure prevents therapeutic energy from being delivered at an inappropriate time, as sporadic low heart rates may indicate erroneous readings.

[0286] In some embodiments, the generator 108 modifies energy delivery based on information from the cardiac monitor 110. For example, in some embodiments, when the heart rate is within a predetermined range, such as between 40 bpm and 120 bpm, energy delivery is provided at a 1:1 ratio. This includes delivery of PEF energy at appropriate intervals after each heartbeat. In some embodiments, when the heart rate exceeds this range, such as when the heart rate exceeds 120 bpm, the generator 108 modifies energy delivery. In some embodiments, energy delivery is modified to a 2:1 ratio (2 heartbeats:1 delivery), with PEF energy delivered at appropriate intervals after every other heartbeat. It may be appreciated that various ratios in the form of m:n (m and n are integers), such as 3:1, 3:2, 4:1, 4:3, 5:1, etc., may be utilized. It may also be appreciated that in some embodiments, the heart rate may be paced to achieve a desired heart rate. Such pacing may be provided by a separate or integrated pacemaker. In some embodiments, such pacing is provided by a catheter positioned in the coronary sinus, which is used for recording during the procedure but can also be used for pacing. Such pacing can be triggered by the generator 108 or the cardiac monitor 110.

[0287] In some embodiments, the generator 108 stops or modifies energy delivery based on information from other sources, such as from various sensors, including temperature sensors, impedance sensors, contact or contact force sensors, etc. In some embodiments, the generator 108 modifies energy delivery based on the temperature being sensed (e.g., on the catheter 102, in nearby tissue, in nearby structures, etc.). In some embodiments, the energy delivery is modified to a 2:1 ratio, such that once the temperature reaches a predetermined threshold, PEF energy is delivered at an appropriate interval of every other heartbeat. Such a modification reduces small thermal effects, thereby lowering the detected temperature. It can be appreciated that various ratios may be utilized, such as 3:1, 3:2, 4:3, 4:1, 5:1, etc.

[0288] As previously mentioned, one or more energy delivery algorithms 152 can be programmable or pre-programmed into the generator 108 for delivery to the patient P. The one or more energy delivery algorithms 152 specify electrical signals that provide energy delivered to cardiac tissue that is non-thermal (e.g., below the threshold for thermal ablation, below the threshold for inducing coagulative thermal damage), reduces or avoids inflammation, and / or prevents denaturation of interstitial proteins in luminal structures. It can be appreciated that non-thermal energy is also not cryogenic (i.e., above the threshold for thermal damage caused by freezing). Thus, the temperature of the target tissue remains in a range between baseline body temperature (such as 35°C to 37°C, but can be reduced to 30°C) and the threshold for thermal ablation. Thus, 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, cardiac tissue lesions are not created by thermal injury because the tissue temperature remains below the thermal ablation threshold (e.g., 65°C). Furthermore, tissue impedance is typically below the threshold produced by thermal ablation. Charring and burning of the tissue alters the electrical conductivity of the cardiac tissue. This increase in impedance / decrease in conductivity often indicates a burn and reduces the tissue's ability to receive further energy. In some cases, the impedance of the system circuit from the cathode to the anode remains in the 25-250 Ω or 50-200 Ω range during delivery of PEF energy. Generally, algorithm 152 is tuned to affect tissue to a predetermined depth and / or volume and / or to target specific types of cellular responses to the delivered energy. However, it can be appreciated that the pulsed electric field energy described herein can be utilized more liberally than other types of energy, such as those that cause burns, without negative effects. For example, because the energy does not cause a burn, tissue can be overtreated to ensure sufficient lesion formation. For example, in a 2 mm thick tissue layer, sufficient energy can be applied to the tissue to create a 6 mm deep lesion, ensuring a transmural lesion.Typically, additional energy is dissipated from nearby critical structures via lateral tissue planes. In particular, the pericardial effusion surrounding the heart helps dissipate energy and protect extracardiac structures, such as the esophagus, phrenic nerve, coronary arteries, lungs, and bronchioles, from injury. This is not the case when delivering energy to create lesions via thermal injury. In these cases, conductive thermal energy propagation beyond the targeted myocardial tissue can result in thermal injury to non-targeted extracardiac structures. Excessive thermal injury to the esophagus can cause esophageal ulcers that can resolve into life-threatening atrioesophageal fistulas. Thermal injury to the phrenic nerve can cause permanent diaphragmatic paralysis, resulting in persistent shortness of breath and fatigue. Thermal injury to the coronary arteries can cause coronary artery spasm, which can lead to temporary or permanent chest pressure / pain. Additionally, cardiac thermal lesions in the region of 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 injury to the tissue, which induces postoperative fibrosis and scarring. Stenosis has been described in patients treated with many forms of thermal energy, including radiofrequency energy and cryoablation.

[0289] Because the PEF lesions described here are not caused by burns, the rate of "false-positive" confirmation of electrical conduction block is also reduced. Burns can cause acute myocardial edema (i.e., tissue fluid accumulation and swelling). When testing electrical conductivity across an area of ​​tissue being thermally ablated, the tissue may appear to block electrical conduction, but such blockage may simply be the result of temporary edema. After a recovery period during which the swelling subsides, this area of ​​treated tissue is no longer transmural and non-conductive. Furthermore, acute edema from burns also reduces the ability to re-treat an area of ​​tissue. Once an area of ​​tissue receives a degree of burn, the resulting edema alters the tissue's resistive and conductive thermal properties. Therefore, it is difficult to achieve an effect similar to the tissue's initial response. Attempted re-treatments are therefore less effective both acutely and chronically. These issues are avoided by the energy delivery described here.

[0290] Figure 3 shows a portion of the heart H, showing the right atrium (RA) and left atrium (LA) section for the treatment of atrial fibrillation. The four major pulmonary veins (the right superior pulmonary vein (RSPV), the right superior pulmonary vein (RIPV), the left superior pulmonary vein (LSPV), and the left inferior pulmonary vein (LIPV)), two from each lung, drain into the left atrium (LA) of the heart H. Each pulmonary vein is linked to the capillary network of the alveoli of each lung and carries oxygenated blood to the left atrium (LA). The left atrial musculature extends from the left atrium (LA) and encases the proximal pulmonary veins. Superior veins, which have a longer muscular sleeve, have been reported to induce arrhythmias more frequently than inferior veins. Generally, the length of the pulmonary vein sleeve varies from 13 mm to 25 mm. Pulmonary vein morphology has been reported to influence the generation of arrhythmias. Similarly, cellular electrophysiology and other aspects of the pulmonary veins are related to the generation and propagation of arrhythmias.

[0291] Various methods are used to determine the tissue to be treated, including anatomical adaptation and cardiac mapping. Typically, a mapping catheter is selected to accommodate the size and anatomy of the pulmonary veins to ensure a desirable fit within the pulmonary veins. The mapping catheter allows for the recording of electrograms from the pulmonary vein ostium and from deep within the pulmonary veins, which are displayed and timed for the user. The treatment catheter 102 is first placed deep within the pulmonary vein and gradually withdrawn to the ostium proximal to the mapping catheter. Mapping and treatment then begin.

[0292] The current understanding of pulmonary vein electrophysiology is that most pulmonary vein fibers are circular and do not carry intravenous conduction. The electrical conduction pathway is the longitudinal fibers extending between the left atrium (LA) and the pulmonary veins. Pulmonary vein isolation is achieved by ablation of these connecting longitudinal fibers. In the case of left-sided pulmonary veins, distal coronary sinus pacing tends to increase the separation of the atrial signal and the pulmonary vein potential, making them more electrically visible. Signals from within the pulmonary veins are evaluated. Each individual signal consists of a generally small-amplitude far-field atrial signal and a sharp, localized pulmonary vein spike. The earliest pulmonary vein spike represents the site of pulmonary vein-atrium connection. Examination of the pulmonary vein spike and atrial potential reveals significant separation of these electrograms at some poles of the mapping catheter, while at other sites there is fusion of the atrial and PV signals. The latter indicates the location of the longitudinal fibers and a potential site for treatment.

[0293] In some embodiments, tissue surrounding the opening of the left inferior pulmonary vein (LIPV) is treated in a point-by-point manner using the treatment catheter 102 (with the aid of mapping), creating a circular treatment zone around the left inferior pulmonary vein (LIPV), as illustrated in FIG. 3 . In some cases, specialized navigation software can be used to facilitate proper positioning of the treatment catheter 120. A delivery electrode 122 is positioned near or opposite the target tissue region, and energy is delivered to the delivery electrode 122 to create treatment region A. Because energy is delivered to a localized region (focal delivery), the electrical energy is concentrated over a smaller surface area, resulting in a stronger effect than delivery via electrodes extending circumferentially around the lumen or ostium. Additionally, the electrical energy is delivered in a stepwise, localized approach, reducing the potential impact of preferential current paths through surrounding tissue. These preferential current paths are regions with electrical properties that induce increased current flow locally, rather than in adjacent regions. Such a path can result in an irregular current distribution around the target lumen, distorting the electric field and causing irregular increases in treatment efficacy in some areas and decreases in other areas. This can be mitigated or avoided by using localized therapy to stabilize the treatment effect around the target area. Therefore, by providing energy to a specific area at a time, the electrical energy is "forced" to various surrounding areas, improving the circumferential regularity of the treatment. Figure 4 illustrates the repeated application of energy point-by-point around the left inferior pulmonary vein (LIPV) using a treatment catheter 102 to create a circular treatment zone. As shown, in this embodiment, each treatment area A overlaps with adjacent treatment areas A to create a continuous treatment zone. The size and depth of each treatment area A may depend on various factors, such as parameter values, treatment time, and tissue characteristics. It may be understood that the number of treatment areas A may vary depending on various factors, particularly the unique anatomy and electrophysiology of each patient. In some embodiments, the number of treatment areas A includes 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30 or more.

[0294] Once all electrical connections between the atria and veins have been addressed, there is electrical silence within the pulmonary veins, and only far-field atrial signals are recorded. Occasionally, spikes of electrical activity are seen within the pulmonary veins, with no conduction to the rest of the atrium; these clearly indicate electrical discontinuity of the veins from the rest of the atrial myocardium.

[0295] Depending on the clinical presentation, additional treatment areas can be created elsewhere to treat right or left atrial arrhythmias. Tests are then performed to confirm that each targeted pulmonary vein is effectively isolated from the left atrium. Energy Delivery Algorithm

[0296] It can be appreciated that a variety of energy delivery algorithms 152 can be used. In some embodiments, the algorithm 152 defines a signal having a waveform including a series of energy packets, each containing a series of high-voltage pulses. In such embodiments, the algorithm 152 specifies parameters of the signal, such as the energy amplitude (e.g., voltage) and duration of applied energy, consisting of the number of packets, the number of pulses within a packet, and the fundamental frequency of the pulse sequence, to name a few. Additional parameters can include the switching time between polarities of the biphasic pulses, the dead time between biphasic cycles, and the rest time between packets, which are described in more detail in later sections. There can be a fixed rest period between packets, or the packets can be gated to the cardiac cycle and therefore variable depending on the patient's heart rate. There can be an intentionally varying rest period algorithm, or no rest period can be applied between packets. Feedback loops based on sensor information, automatic shut-off specifications, and the like can be included.

[0297] FIG. 5 illustrates an embodiment of a waveform 400 of a signal prescribed by the energy delivery algorithm 152. Two packets are shown: a first packet 402 and a second packet 404, separated by a pause period 406. In this embodiment, each packet 402, 404 is composed of a first biphasic cycle (including a first positive pulse peak 408 and a first negative pulse peak 410) and a second biphasic cycle (including a second positive pulse peak 408' and a second negative pulse peak 410'). The first and second biphasic pulses are separated by a dead time 412 (i.e., a pause) between each pulse. In this embodiment, the biphasic pulses are symmetric, resulting in a set voltage 416 that is the same for the positive and negative peaks. The biphasic symmetric wave is also a square wave, such that the magnitude and duration of the positive voltage wave are approximately equal to the magnitude and duration of the negative voltage wave.

[0298] A. Voltage The voltages used and considered can be the crest of a square wave, the peak of a sine wave or sawtooth wave, or the RMS voltage of a sine wave or sawtooth wave. In some embodiments, the energy is delivered in a monopolar manner and each high voltage pulse or set voltage 416 is between about 500V and 10,000V, particularly between about 1000V and 2000V, 2000V and 3000V, 3000V and 3500V, 3500V and 4000V, 3500V and 5000V, and 3500V and 6000V, to name a few, including all values ​​and subranges therebetween, including 1000V, 2000V, 2500V, 2800V, 3000V, 3300V, 3500V, 3700V, 4000V, 4500V, 5000V, 5500V, and 6000V.

[0299] It can be appreciated that the set voltage 416 can vary depending on whether the energy is delivered monopolarly or bipolarly. With bipolar delivery, a lower voltage can be used due to a smaller, more directed electric field. While the bipolar voltage selected for treatment depends on the electrode separation distance, a monopolar electrode configuration using one or more separate dispersive pad electrodes can be delivered without significant consideration for the precise placement of the catheter electrode and the dispersive electrode in the body. In monopolar electrode embodiments, due to the dispersive behavior of the energy delivered through the body, a larger voltage is generally used, reaching the dispersive electrode at an effective separation distance of approximately 10 cm to 100 cm. Conversely, in bipolar electrode configurations, the relatively close active area of ​​the electrodes is on the order of 0.5 mm to 10 cm, including 1 mm to 1 cm, which significantly impacts the electrical energy concentration and effective dose delivered to the tissue from the separation distance. For example, if the target voltage-to-distance ratio is 3000 V / cm and causes the desired clinical effect at the appropriate tissue depth (1.3 mm), changing the separation distance from 1 mm to 1.2 mm will result in a required increase in treatment voltage from 300 to approximately 360 V, a change of 20%.

[0300] B.Frequency The number of biphasic cycles per second of time can be understood to be the frequency of the signal when it is continuous. In some embodiments, biphasic pulses are utilized to reduce undesired muscle stimulation, particularly myocardial stimulation. In other embodiments, the pulse waveform is monophasic and does not have a distinct natural frequency. Instead, the fundamental frequency can be considered by doubling the monophasic pulse length to derive the frequency. In some embodiments, the signal has a frequency in the range of 50 kHz to 1 MHz, more specifically, 50 kHz to 1000 kHz. It can be understood that at some voltages, frequencies below 100 to 250 kHz may cause undesired muscle stimulation. Thus, in some embodiments, the signal has a frequency in the range of 300 to 800 kHz, 400 to 800 kHz, or 500 to 800 kHz, e.g., 300 kHz, 400 kHz, 450 kHz, 500 kHz, 550 kHz, 600 kHz, 650 kHz, 700 kHz, 750 kHz, 800 kHz, etc. Furthermore, cardiac synchronization is typically utilized to reduce or avoid unwanted myocardial stimulation during sensitive rhythm periods. It can be appreciated that even higher frequencies can be used with components that minimize signal artifacts.

[0301] C. Voltage-Frequency Balance The frequency of the delivered waveform can be varied in sync with the treatment voltage to maintain the appropriate therapeutic effect. Such synergistic variations include lowering the frequency to produce a stronger effect and lowering the voltage to produce a weaker effect. For example, in some cases, treatment can be delivered using 3000V in a monopolar fashion with a waveform frequency of 600kHz, while in other cases, treatment can be delivered using 2000V with a waveform frequency of 400kHz.

[0302] D. Packet As previously discussed, the algorithm 152 typically defines a signal having a waveform including a series of energy packets, each of which includes a series of high-voltage pulses. The cycle count 420 is half the number of pulses in each biphasic packet. Referring to FIG. 5, the first packet 402 has a cycle count 420 of two (i.e., four biphasic pulses). In some embodiments, the cycle count 420 is set from 2 to 1000 per packet, including all values ​​and subranges therebetween. In some embodiments, the cycle count 420 is between 5 and 1000 per packet, between 2 and 10 per packet, between 2 and 20 per packet, between 2 and 25 per packet, between 10 and 20 per packet, between 20 and 30 per packet, between 25 per packet, between 20 and 40 per packet, between 30 per packet, between 20 and 50 per packet, between 30 and 60 per packet, up to 60 per packet, up to 80 per packet, up to 100 per packet, up to 1,000 per packet, or up to 2,000 per packet, including all values ​​and subranges therebetween.

[0303] Packet duration is determined by, among other factors, cycle count. For matching pulse durations (or sequences of positive and negative pulse durations in the case of biphasic waveforms), the higher the cycle count, the longer the packet duration and the greater the amount of delivered energy. In some embodiments, packet durations are in the range of about 50-1000 microseconds, e.g., 50 μs, 60 μs, 70 μs, 80 μs, 90 μs, 100 μs, 125 μs, 150 μs, 175 μs, 200 μs, 250 μs, 100-250 μs, 150-250 μs, 200-250 μs, or 500-1000 μs, to name a few. In other embodiments, packet durations are in the range of about 100-1000 microseconds, such as 150 μs, 200 μs, 250 μs, 500 μs, or 1000 μs.

[0304] The number of packets, or packet count, delivered during a treatment typically ranges from 1 to 250 packets, including all values ​​and subranges therebetween, hi some embodiments, the number of packets delivered during a treatment includes 10 packets, 15 packets, 20 packets, 25 packets, 30 packets, or more than 30 packets.

[0305] E. Break Period In some embodiments, the time between packets, referred to as the idle period 406, is set between about 0.001 seconds and about 5 seconds, including all values ​​and subranges therebetween. In other embodiments, the idle period 406 ranges between about 0.01 and 0.1 seconds, including all values ​​and subranges therebetween. In some embodiments, the idle period 406 is between about 0.5 ms and 500 ms, between 1 and 250 ms, or between 10 and 100 ms, to name a few.

[0306] F. Batch In particular, in some embodiments, the signal is synchronized with the heart rhythm, such that each packet is delivered synchronously within a specified period relative to the heartbeat, and therefore coincides with the heartbeat for the remaining period. It can be appreciated that the packets delivered within each specified period relative to the heartbeat can be considered a batch or bundle. Thus, each batch has a desired number of packets, such that at the end of the therapy period, a desired total number of packets has been delivered. While each batch can have the same number of packets, in some embodiments, the batches have different numbers of packets.

[0307] In some embodiments, only one packet is delivered between heartbeats. In such cases, the pause period can be considered the same as the period between batches. However, if multiple packets are delivered between batches, the remaining time is typically different from the period between batches. In such cases, the pause period is typically much shorter than the period between batches. In some embodiments, each batch includes, to name a few, 1-10 packets, 1-5 packets, 1-4 packets, 1-3 packets, 2-3 packets, 2 packets, 3 packets, 4 packets, 5 packets, or 5-10 packets. In some embodiments, each batch has a duration of 0.5 ms to 1 sec, 1 ms to 1 sec, 10 ms to 1 sec, or 10 ms to 100 ms, to name a few. In some embodiments, the period between batches is variable depending on the patient's heart rate. In some cases, the period between batches is 0.25 to 5 seconds.

[0308] Treatment of the tissue region continues until the desired number of batches have been delivered to the tissue region. In some embodiments, 2-50 batches are delivered per treatment, with a treatment being considered treatment of a particular tissue region. In other embodiments, a treatment may 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.

[0309] G. Switching Times and Dead Times The switching time is the delay or period of time during which no energy is delivered between the positive and negative peaks of a biphasic pulse, as illustrated in FIG. 5. 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 some embodiments, the switching time ranges from about 2 to about 8 microseconds, including all values ​​and subranges therebetween.

[0310] A delay may also be inserted between each biphasic cycle, referred to as "dead time." Dead time occurs within a packet, but occurs between biphasic pulses. This contrasts with the rest periods that occur between packets. In other embodiments, dead time 412 ranges from about 0 to 0.5 microseconds, 0 to 10 microseconds, 2 to 5 microseconds, 0 to 20 microseconds, about 0 to about 100 microseconds, or about 0 to about 100 milliseconds, including all values ​​and subranges therebetween. In some embodiments, dead time 412 ranges from 0.2 to 0.3 microseconds. Dead time may also be used to define the period between separate monophasic pulses within a packet.

[0311] Delays such as switching times and dead times are introduced into the packets to reduce the effects of biphasic cancellation in the waveform. In some cases, both the switching time and dead time are increased simultaneously to enhance the effect. In other instances, only the switching time or only the dead time is increased to induce this effect.

[0312] G. Waveform FIG. 5 illustrates an embodiment of a waveform 400 having symmetric pulses such that the voltage and duration of the pulse in one direction (i.e., positive or negative) are equal to the voltage and duration of the pulse in the other direction. FIG. 6 illustrates an exemplary waveform 400 defined by another energy delivery algorithm 152, in which the waveform 400 has a voltage imbalance. Here, two packets are shown: a first packet 402 and a second packet 404, separated by a rest period 406. In this embodiment, each packet 402, 404 is comprised of a first biphasic cycle (including a first positive pulse peak 408 having a first voltage V1 and a first negative pulse peak 410 having a second voltage V2) and a second biphasic cycle (including a second positive pulse peak 408' having a first voltage V1 and a second negative pulse peak 410' having a second voltage V2). Here, the first voltage V1 is greater than the second voltage V2. The first and second biphasic cycles are separated by a dead time 412 between each pulse. Therefore, because the voltage in one direction (i.e., positive or negative) is greater than the voltage in the other direction, 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 can produce a more pronounced therapeutic effect because the dominant positive or negative amplitude increases the duration of the same charge cell membrane charge potential. In this embodiment, the first positive peak 408 has a set voltage 416 (V1) that is greater than the set voltage 416' (V2) of the first negative peak 410. Figure 7 illustrates a further example of a waveform with unequal voltages. Here, four different types of packets are summarized in one diagram. The first packet 402 has pulses of unequal voltage but equal pulse width, with no switching time or dead time. Thus, the first packet 402 consists of four biphasic pulses, each including a positive peak 408 having a first voltage V1 and a negative peak 410 having a second voltage V2, where the first voltage V1 is greater than the second voltage V2. The second packet 404 consists of pulses having unequal voltages but symmetric pulse widths (as in the first pulses 402), with a switching time equal to the dead time.The third packet 405 consists of pulses with unequal voltages but symmetric pulse widths (as in the first pulse 402), with a switching time shorter than the dead time. The fourth packet 407 consists of pulses with unequal voltages but symmetric pulse widths (as in the first pulse 402), with a switching time longer than the dead time. In some embodiments, the positive and negative phases of the biphasic waveform are not identical but are balanced, with the voltage in one direction (i.e., positive or negative) greater than the voltage in the other direction, but the pulse lengths are calculated so that the area under the curve for the positive phase is equal to the area under the curve for the negative phase.

[0313] In some embodiments, the imbalance includes pulses having pulse widths that are unequal in duration. In some embodiments, a biphasic waveform is imbalanced such that the voltage in one direction is equal to the voltage in the other direction, but the duration of one direction (i.e., positive or negative) is longer than the duration of 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 negative portion of the waveform.

[0314] FIG. 8 illustrates further examples of waveforms with unequal pulse widths. Here, four different types of packets are summarized in one diagram. The first packet 402 consists of pulses with equal voltages but different pulse widths, and there is no switching time or dead time. Thus, the first packet 402 consists of four biphasic 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 packet 404 consists of pulses with equal voltages but unequal pulse widths (as in the first pulses 402), and the switching time is equal to the dead time. The third packet 405 consists of pulses with equal voltages but unequal pulse widths (as in the first pulses 402), and the switching time is shorter than the dead time. The fourth packet 407 consists of pulses with equal voltages but unequal pulse widths (as in the first pulses 402), with switching times longer than the dead time.

[0315] FIG. 9 illustrates an exemplary waveform 400 defined by another energy delivery algorithm 152 in which the waveform is monophasic, a special case of imbalance where there is only a positive or negative portion of the waveform. Two packets, a first packet 402 and a second packet 404, are shown, separated by a rest period 406. In this embodiment, each packet 402, 404 is composed of a first monophasic pulse 430 and a second monophasic pulse 432. The first and second monophasic pulses 430, 432 are separated by a dead time 412 between each pulse. This monophasic waveform may produce more desirable therapeutic effects because the same charge cell membrane potential is maintained for a longer period. However, adjacent muscle groups are stimulated more with a monophasic waveform compared to a biphasic waveform.

[0316] FIG. 10 illustrates a further example of a waveform with monophasic pulses. Here, four different types of packets are summarized in one diagram. The first packet 402 consists of pulses with the same voltage and pulse width, with no switching time (because the pulses are monophasic), and a dead time equal to the active time. In some cases, the dead time period may be shorter than the active time of a particular pulse. Thus, the first packet 402 consists of three monophasic pulses 430, each containing a positive peak. If the dead time is equal to the active time, the waveform represents a cycle period twice the active time and can be considered unbalanced at the fundamental frequency with no dead time. The second packet 404 consists of monophasic pulses 430 with the same voltage and pulse width (as in the first packet 402) but with a larger dead time. The third packet 405 consists of monophasic pulses 430 with the same voltage and pulse width (as in the first packet 402) and an even larger dead time. The fourth packet 407 consists of monophasic pulses 430 with equal voltage and pulse width (as in the first packet 402), but with a larger dead time.

[0317] In some embodiments, an unbalanced waveform is achieved by delivering two or more pulses of one polarity before reversing to an unequal number of pulses of the opposite polarity. Figure 11 illustrates further examples of waveforms with such phase imbalances. Here, four different types of packets are summarized in one diagram. The first packet 402 consists of four cycles with equal voltage and pulse width, but pulses of opposite polarity are mixed with monophasic pulses. Thus, the first cycle includes a positive peak 408 and a negative peak 410. The second cycle is monophasic and includes a single positive pulse without a subsequent negative pulse 430. This repeats. The second packet 404 consists of mixed biphasic and monophasic cycles (as in the first packet 402), but the pulses have unequal voltages. The third packet 405 consists of mixed biphasic and monophasic cycles (as in the first packet 402), but the pulses have unequal pulse widths. The fourth packet 407 consists of intermixed biphasic and monophasic pulses (as in the first packet 402), but the pulses have unequal voltages and unequal pulse widths. Thus, multiple combinations and permutations are possible.

[0318] H.Wave shape FIG. 12 illustrates an exemplary wave 400 defined by another energy delivery algorithm 152 in which the pulses are sinusoidal rather than square. Similarly, two packets are shown: a first packet 402 and a second packet 404, separated by a rest period 406. In this embodiment, each packet 402, 404 is composed of three biphasic pulses 440, 442, 444. Instead of a square wave, these pulses 440, 442, 444 are sinusoidal. One advantage of a sinusoidal waveform is that it is balanced, or symmetrical, so each phase is equal in shape. Balancing helps reduce unwanted muscle stimulation. It may be appreciated that in other embodiments, the pulses have decaying waveforms.

[0319] Energy delivery can be activated by a variety of mechanisms, such as using a button 164 on the catheter 102 or a footswitch 168 operably connected to the generator 104. Such activation typically provides a single energy dose. The energy dose is defined by the number of packets delivered and the voltage of the packets. Each energy dose delivered to tissue maintains the temperature within or within the tissue below the threshold for thermal ablation. Additionally, the dose can be titrated or relaxed over time to further reduce or eliminate heat buildup during the treatment procedure. Instead of inducing thermal damage, defined as protein coagulation at sites critical to treatment, the energy dose provides a level of energy that induces treatment of the condition without damaging sensitive tissue.

[0320] Use of conventional ablation catheters In some circumstances, it may be desirable to utilize 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 in place of catheter 102 to deliver the high-voltage pulsed electric fields described herein, either alone or in combination with the delivery of other energies, such as conventional ablation energies. Examples of conventional ablation catheters include radiofrequency catheters typically used to treat atrial fibrillation, radiofrequency catheters typically used to treat other cardiac arrhythmias, microwave catheters, and the like. Examples include, but are not limited to, the following:

[0321] 1) Catheters and devices by Abbott Laboratories (Chicago, IL), including Livewire™ TC Ablation Catheter, Safire™ Ablation Catheter, Safire™ TX Ablation Catheter, Therapy™ Ablation Catheter, FlexAbility™ Ablation Catheter, Sensor Enabled™, FlexAbility™ Irrigated Ablation Catheter, TactiCath™ Contact Force Irrigated Ablation Catheter, Sensor Enabled™, TactiCath™ Quartz Contact Force Ablation Catheter, and Therapy™ Cool Path™ Ablation Catheter;

[0322] 2) THERMOCOOL® SMARTTOUCH® SF Unidirectional Catheter, THERMOCOOL® SMARTTOUCH® SF Bidirectional Catheter, THERMOCOOL® SMARTTOUCH® Unidirectional Catheter, THERMOCOOL® SMARTTOUCH® Bidirectional Catheter, THERMOCOOL® SF NAV Unidirectional Catheter, THERMOCOOL® SF NAV Bidirectional Catheter, THERMOCOOL® SF NAV Unidirectional Catheter with Curve Visualization, THERMOCOOL® SF NAV Bidirectional Catheter with Curve Visualization, NAVISTAR® THERMOCOOL® Unidirectional Catheter, NAVISTAR® THERMOCOOL® Bidirectional Catheter, NAVISTAR® 4mm Catheter, NAVISTAR® DS Catheter, NAVISTAR® RMT THERMOCOOL® Catheter, NAVISTAR® RMT 4mm Catheter, THERMOCOOL® SF Unidirectional Catheter, THERMOCOOL® SF catheters and devices by Biosense Webster Inc. (Irvine, CA), including bidirectional catheters, EZ STEER® THERMOCOOL® catheters, EZ STEER® 4mm bidirectional catheters, EZ STEER® DS bidirectional catheters, CELSIUS® THERMOCOOL® unidirectional catheters, CELSIUS® RMT THERMOCOOL® catheters, CELSIUS® 4mm catheter thermocouples, CELSIUS® 4mm catheter thermistors, CELSIUS® 4mm braided-tip catheters, CELSIUS FLTR® 8mm unidirectional catheters, CELSIUS FLTR® 8mm bidirectional catheters, CELSIUS® DS catheters, and CELSIUS® RMT catheters;

[0323] 3) Catheters and devices by Boston Scientific Corporation (Marlborough, MA) and / or BARD EP, including the BLAZER PRIME™ Temperature Ablation Catheter, the BLAZER™ II Temperature Ablation Catheter Family, the BLAZER™ Open-Irrigated Temperature Ablation Catheter, the INTELLANAV™ XP & INTELLANV MIFI™ XP Temperature Ablation Catheter Family, the INTELLANAV™ ST Ablation Catheter, the INTELLANAV™ OPEN-Irrigated Ablation Catheter, the INTELLATIP MIFI™ XP Temperature Ablation Catheter, the INTELLATIP MIFI™ Open-Irrigated Ablation Catheter, and the INTELLANAV™ ST Ablation Catheter;

[0324] 4) Catheters and devices by Medtronic Inc. (Fridley, Minnesota), including the 7 Fr RF Marinr™ MC catheter, 5 Fr RF Marinr™ catheter, RF Contactr™ catheter, RF Enhancr™ II catheter, and RF Conductr™ MC catheter;

[0325] 5) Catheters and devices by Access Point Technologies EP Inc. (Rogers, MN), including the EP Map-iT™ catheter and Map-iT™ irrigated ablation catheter;

[0326] 6) Catheters and devices by Synaptic Medical Inc. (Lake Forest, CA), including the Rithm Cool™ Irrigated Tip Ablation Catheter, the Rithm Rx® Deflectable Ablation Catheter, and the AquaSense® Microinfusion Irrigated Tip Ablation Catheter;

[0327] 7) Catheters and devices by Osypka Medical GmbH (Berlin, Germany) / Cardiotronic-Osypka Medical, Inc. (La Jolla, CA), including Cerablate® easy / Cerablate® easy TC, Cerablate cool®, and Cerablate flutter®;

[0328] 8) Catheters and devices by Biotronik GmbH & Co (Berlin, Germany) and / or Acutus Medical Inc (Carlsbad, CA), including AlCath Gold FullCircle, AlCath Flutter Gold, and AlCath Flux eXtra Gold;

[0329] 9) Catheters and devices by Atricure Inc. (Mason, OH), including Isolator Synergy Clamps, Isolator Synergy Access Clamp, COBRA Fusion 150 Ablation System, Coolrail Linear Pen, Isolator Linear Pen, and Isolator Transpolar Pen;

[0330] 10) Catheters and devices by OSCORInc (Palm Harbor, FL).

[0331] 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 do not function under high-voltage energy delivery conditions. Such failures can render these features and mechanisms ineffective and lead to overall device failure. For example, many conventional ablation catheters have multiple electrodes near their distal end. FIG. 13 illustrates an embodiment of a conventional ablation catheter 101 including a shaft 121 having a distal tip electrode 123 and multiple ring electrodes 127 near the distal end of the shaft, proximal to the distal tip electrode 123. In this embodiment, the catheter 101 includes a contact force sensor 181 located proximal to the distal tip electrode 123 and three internal fiber optic cables within the shaft 121. Additionally, the catheter 101 includes an electromagnetic sensor 191 located proximal to the distal tip electrode for integration with a cardiac mapping system. Furthermore, the catheter 101 has a handle 129 located 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 a tension lock that allows variable control. The handle 129 has an integrated cable 133 for connecting to the generator 108 or the like.

[0332] Because each electrode in catheter 101 is generally intended to be independently activated, each of electrodes 123, 127 has its own conductive wire that extends through the catheter to its proximal end. These conductive wires are contained within the body of the catheter and are typically each surrounded by an insulating layer to prevent undesired short circuits between conductors.

[0333] However, when delivering the pulsed electric field energy described herein, these conventional ablation catheters 101 are often prone to arcing and short circuits. This is caused by the high-voltage energy delivered through the various conductors within the conventional catheter. Because conventional ablation catheters 101 are designed for lower voltages, the conductive wires are not arranged to insulate them from one another, and the insulating material used is insufficient to properly insulate the conductive wires under these conditions. As a result, the insulating material fails, causing the conductive wires to short out to one another and resulting in arcing within the catheter body. All of these issues 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.).

[0334] FIG. 14A illustrates some of the problems associated with high-voltage energy delivery via a conventional ablation catheter having multiple electrodes, such as the catheter 101 illustrated in FIG. 13 . Here, the distal end of the catheter 101 is shown having an elongated shaft 121 with a delivery electrode 123 at its distal tip. In this embodiment, the catheter 101 includes three additional ring electrodes: a secondary electrode 127 a, a tertiary electrode 127 b, and a quaternary electrode 127 c, each spaced an incremental distance proximally along the shaft 121 from the delivery electrode 123. During use, the delivery electrode 123 is positioned relative to target tissue T, such as cardiac tissue. Energy being delivered via the delivery electrode 123 enters the tissue T as shown. However, when treating cardiac tissue, the environment is typically filled with blood. Due to the electrical conductivity of blood, energy is transmitted through conductive wires to the secondary electrode 127 a, the tertiary electrode 127 b, and the quaternary electrode 127 c, as indicated by the arrows in FIG. 14A .

[0335] As the current (J) passes through the medium (blood or tissue) according to its electrical conductivity (σ), the voltage drops from the active electrode (voltage V=V0) to the ground electrode (V=0).

number

[0336] The expected voltage at each electrode can be obtained using a numerical approach. Analytical solutions are only feasible if simple geometries and uniform conductivity are employed. However, because the geometries of both the tissue and the electrodes can be complex, it is more likely that the finite element method will be used to determine the voltage distribution and solve for the potential (V) that satisfies the following Laplace equation:

number

[0337] Using this method, the voltages of the delivery electrode 123, secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c can be determined. The delivery electrode 123 has the maximum voltage, and the voltage value decreases with distance from the delivery electrode 123. Because all electrodes are connected to internal conductive wires, their respective voltages can be extracted from the calculated value, and thus the maximum voltage difference between them can be determined. For example, if the energy delivered to the delivery electrode 123 has a voltage of 3300 V, the energy transferred to the secondary electrode 127a may have a voltage of 1450 V, the energy transferred to the tertiary electrode 127b may have a voltage of 1050 V, and the energy transferred to the quaternary electrode 127c may have a voltage of 950 V. This presents various problems. First, each of the electrodes 123, 127a, 127b, and 127c is connected to the proximal end of the catheter 101 by an insulated conductive wire. FIG. 14B illustrates a cross section of shaft 121 showing insulated conductive wires 123′, 127a′, 127b′, and 127c′ corresponding to electrodes 123, 127a, 127b, and 127c. In conventional ablation catheters, such insulation is not sufficient to insulate beyond a voltage difference of approximately 1500 V (although this value may vary depending on the specific design of the catheter). In the example shown in FIG. 14A, the difference between delivery electrode 123 and secondary electrode 127a is 1850 V, the difference between delivery electrode 123 and tertiary electrode 127b is 2250 V, and the difference between delivery electrode 123 and quaternary electrode 127c is 2350 V. If each of these exceeds the 1500 V threshold, an insulation failure occurs, resulting in a short circuit and arcing between the conductive wires.

[0338] The voltage can be reduced below the threshold level for short circuits and / or arcing using various systems and methods. For example, in some embodiments, each of the electrodes 123, 127a, 127b, and 127c is set to the same voltage. Because each conductive wire is at the same potential, the voltage difference between the conductive wires is zero, and arcing cannot occur. However, this simple solution has several disadvantages. First, activating all of the electrodes 123, 127a, 127b, and 127c in this manner can result in each delivering therapeutic energy, potentially delivering energy to undesired areas. Second, for the same applied voltage, the total current injected into the body is higher, potentially resulting in excessive temperature or muscle stimulation. Furthermore, such high current demands require improved pulse generator performance.

[0339] In other embodiments, a component network 111, such as one comprised of passive components (e.g., resistors, inductors, 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 direct energy through the conductive lines in a predetermined manner so that the voltage difference remains below a certain threshold level, such as 1500 V. In some embodiments, the component network 111 is disposed, for example, within the generator 108 to which the catheter 101 is coupled for energy delivery, in a separate device in line with the generator 108 (e.g., interface connector 10), or within the catheter 101 or an attachment to the catheter 101.

[0340] The values ​​of resistor, capacitor, and inductor impedances can vary depending on various factors, such as 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 particular set of applied energy parameters, such as voltage, amplitude, and frequency, a complex impedance can be predetermined to modulate the energy flowing from the pulse generator to the electrodes.

[0341] 15, a first resistor R1 is positioned between conductive line 123' (coupled to delivery electrode 14) and conductive line 127a' (coupled to secondary electrode 127a). Similarly, a second resistor R2 is positioned between conductive line 123' (coupled to delivery electrode 123) and conductive line 127b' (coupled to tertiary electrode 127b). Furthermore, a third resistor R3 is positioned between conductive line 123' (coupled to delivery electrode 127) and conductive line 127c' (coupled to quaternary electrode 127c).

[0342] The resistor values ​​for resistors R1, R2, and R3 can vary depending on various factors, including the shape and relative position of the electrodes and the electrical conductivity of the surrounding medium. For example, the greater the distance between the active and inactive electrodes, the lower the voltage induced at the inactive electrode when a voltage is applied to the active electrode. If the voltage difference between the active and inactive electrodes is desired to be maintained below a certain value, increasing the distance between particular electrodes will result in a slightly larger induced voltage at the corresponding inactive electrode, remaining within the constraints of the maximum allowable voltage difference. In embodiments with a single inactive electrode, the proposed resistor can be adjusted until the desired voltage is generated at that inactive electrode. However, in embodiments with two or more inactive electrodes, decreasing the value of one resistor will increase the current and induced voltage through that inactive electrode, but may also increase the voltage at the other inactive electrodes. This interdependence between the resulting electrode voltage and resistance values ​​results in a highly complex system.

[0343] This complexity is addressed with a three-dimensional mathematical model of the electrode and the potential environment. This model takes into account the various elements that can be expected in the environment when treating cardiac tissue, especially tissue surrounded by blood. The properties of these elements are therefore specified, which determines the voltage distribution when a voltage is applied.

[0344] The mathematical model defines the voltage (V = V0) at the surface of the active electrode and the current source (I X) is defined as the current source (the integral of the normal current density J along its surface S), depending on the voltage at the electrode surface, the applied voltage of the active electrode, and the selected resistance value.

number

[0345] In this model, potential combinations of resistance values ​​(with defined range and resolution) are determined. A final value is selected that exhibits the desired performance. In the embodiment shown in FIG. 15, the catheter 101 has four electrodes (one active and three inactive), and three resistance combinations (R1, R2, R3) are calculated (e.g., from 0 to 1000 in 10 Ω steps) to maintain the voltage difference according to the maximum voltage difference supported by the conductors / insulators (e.g., 1500 V) and the total current safety of the pulse generator (e.g., less than 40 A).

[0346] In this example, the energy delivered to delivery electrode 123 via conductive 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 of 1000 to 1200 ohms. For example, in one embodiment, the resistance values ​​are R1 = 500Ω, R2 = 300Ω, and R3 = 300Ω. Using these resistance values, the voltage difference between the conductive wires is as shown in Table 1.

[0347] [Table 1]

[0348] As a result, the resistor network can keep the voltage difference below the short circuit and arcing threshold (e.g., 1500 V) while maintaining the desired high voltage energy delivery (e.g., 3500 V) to the delivery electrode 123. In this example, it can be seen that the current flowing through each conductive wire is as shown in Table 2, totaling approximately 40 amperes.

[0349] [Table 2]

[0350] In some cases, the use of a resistor network may create slightly smaller lesions (e.g., up to 30% smaller) in the target tissue, thereby reducing the effectiveness of the treatment. However, this can be compensated for by increasing the treatment intensity (i.e., voltage). This is possible because the resistor network also increases the arcing and short circuit thresholds. In some cases, the resistor network reduces the maximum current density by 20%. Therefore, to compensate for this difference, the applied voltage may be increased by the same amount. Similarly, when using a resistor network, other waveform characteristics may also be increased to adjust the treatment intensity, such as increasing the cycle count, reducing the fundamental frequency of the waveform, integrating various degrees of asymmetry into the waveform, or adding packets.

[0351] 16A and 16B illustrate the increase in the arcing threshold when using the component network 111 of FIG. 15. FIG. 16A corresponds to a situation where the component network 111 is not utilized. The graph shows the current value at which arcing occurred over a series of pulse cycles. In particular, an amount of energy (e.g., 100 cycles) was delivered at a particular current value, and the presence or absence of arcing was observed. If arcing was not observed, the current value was increased. This continued until arcing was observed. Thus, the highest value along the cycle apex (e.g., the apex of the 100th cycle) is the arcing threshold. Thus, as shown in FIG. 16A, when 60 cycles of energy were delivered through the catheter 101 without the component network 111, the arcing threshold occurred at a current value of 22.2 amps or 2100 V (which corresponds to the highest data point along the apex of the 60th cycle). FIG. 16B corresponds to a situation where the component network 111 of FIG. 15 is utilized, where R1=500, R2=300, and R3=300. Here, the graph shows the current values ​​at which arcing occurred over a series of pulse cycles, which can be seen to be higher than the arcing current values ​​of FIG. 16A. In particular, at 60 cycles, the current value was 32.7 amps or 2700 V. This corresponds to a 47% increase in the arcing current threshold. Thus, the use of component network 111 significantly increases the arcing threshold by preventing uncontrolled current flow through secondary electrode 127a, tertiary electrode 127b, and quaternary electrode 127c.

[0352] It should be understood that other systems and devices can be used to function in a manner similar to component network 111. For example, in some embodiments, generator 108 is configured to send appropriate current to the conductor wires within catheter 101 to keep the voltage difference between the conductor wires below the threshold for arcing or damage to catheter 101. In some cases, generator 108 is configured for use with a particular catheter, such as certain conventional radiofrequency catheters listed above. As such, the electrode spacing and other characteristics of the catheter are known. As a result, generator 108 can be pre-programmed or pre-configured to deliver the appropriate energy through each conductor wire appropriate for the particular catheter. For example, when delivering to catheter 101 shown in FIG. 15 , a multi-channel generator can be used to drive the voltages of secondary electrode 127 a, tertiary electrode 127 b, and quaternary electrode 127 c to a lower voltage than the catheter's distal electrode to keep the voltage difference between the conductor wires below the threshold for arcing (e.g., 1500 V). This can be accomplished using a multi-channel generator incorporating two banks of capacitors: a primary bank of capacitors that is charged to drive the delivery of energy to the catheter's delivery electrode 123, and a secondary bank of capacitors that is charged to a lower voltage than the primary capacitor bank and drives the delivery of energy to the secondary, tertiary, and quaternary electrodes 127a, 127b, and 127c. Additionally, additional banks of capacitors can be used to drive different levels of energy to the secondary, tertiary, and quaternary electrodes 127a, 127b, and 127c. In each of these situations, the voltage difference between the conductor wires is maintained below the arcing threshold (e.g., 1500V).

[0353] In some embodiments, the generator is configured for use with a variety of catheters. In some cases, the generator is programmable for use with a specific catheter, allowing the user to indicate which catheter is being used. For example, the generator may display various selectable options from a menu corresponding to known aspects of known catheters or typical catheters, such as electrode number, electrode spacing, catheter type, etc. Once an aspect of identification is selected, the generator utilizes pre-programmed algorithms corresponding to each type of known catheter or set of known features (e.g., electrode placement) to send appropriate currents to the conductor wires within the catheter and keep the voltage difference between the conductor wires below a threshold for arcing or catheter damage. In other embodiments, the catheter aspect is identified by the generator. For example, in some cases, a catheter can be connected to the generator, and the generator can measure, sense, or identify an aspect of the catheter that indicates appropriate energy to deliver through each conductor wire. In some embodiments, the generator delivers a dose of low-voltage energy through each conductor wire to measure the corresponding impedance. The generator then delivers the appropriate current to each conductor wire within the catheter based on the impedance measurement. In some embodiments, the catheter is analyzed by the generator while the catheter is in the treatment environment and / or in a position to provide treatment. Therefore, environmental or situational factors that affect the impedance reading are taken into account. This may include the presence of blood or other conductive liquids. Alternatively or additionally, this may include the location or placement of the device. For example, some devices may have electrodes along a surface, such as an arm, that may be disposed in various positions. Thus, the distance between various electrodes may vary depending on the location of these surfaces. Evaluating the device while positioned at the target location takes these aspects into account. This may result in more accurate delivery of current values ​​through the conductive wires during treatment.

[0354] It will be appreciated that such variability in environmental conditions may also be accommodated by component network 111 rather than the generator itself. In such embodiments, component network 111 may be comprised of one or more potentiometers, rheostats, variable resistors, capacitors, inductors, diodes, etc. In other embodiments, component network 111 may be comprised of multiple resistors selectable by a controller as needed. In either case, a desired resistance is applied to each of the conductive lines, and the R values ​​(R1, R2, R3) are selected based on measurements such as impedance values, per FIG. 15.

[0355] Additionally, in some embodiments, the component network 111 and systems described herein are utilized to shape the electric field delivered by the catheter 101. For example, FIGS. 17A-17C illustrate various electric fields delivered by the catheter 101 using different resistance values. FIGS. 17A-17C illustrate a catheter 101 having a delivery electrode 123, a secondary electrode 127a, a tertiary electrode 127b, and a quaternary electrode 127c near its distal end. In FIG. 17A, the catheter 101 is connected to the component network 111 as in FIG. 16 with R1=10,000 Ω, R2=10,000 Ω, and R3=10,000 Ω (equivalent to not being connected to the component network 111). The resulting electric field 200 has a somewhat rounded shape emanating primarily from the delivery electrode 123. Figure 17B illustrates the same catheter 101 connected to the component network 111 as in Figure 15, with R1 = 500 Ω, R2 = 300 Ω, and R3 = 300 Ω. The resulting electric field 200 shifts to a pear shape, with slightly circular shapes emanating from the delivery electrode 123 and secondary electrode 127a, along with smaller, overlapping slightly circular shapes emanating from the tertiary electrode 127b and quaternary electrode 127c, creating a pear shape. Figure 17C illustrates the same catheter 101 with all electrodes active. The resulting electric field 200 now shifts to a rectangular or elliptical shape extending from electrodes 123, 127a, 127b, and 127c. Thus, by selecting appropriate resistance values, a desired electric field 200 shape can be generated. This also affects the dimensions of the resulting lesion, with the depth and width depending on the shape of the electric field 200.

[0356] As noted above, the component networks 111 and systems described herein may use catheters 101 having a different number of electrodes than the examples provided herein, e.g., 2 electrodes, 3 electrodes, 4 electrodes, 5 electrodes, 6 electrodes, 7 electrodes, 8 electrodes, 9 electrodes, 10 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 networks 111 and systems described herein may be used with catheters 101 having electrode arrangements other than the examples provided herein, such as having different spacing between electrodes and nonlinearly arranging the electrodes, such as around a ring. Alternatively, it will be appreciated that on a branched spline, each containing one or more electrodes, separate electrodes may function as a single electrode if they are adjacent to or sufficiently close to each other and simultaneously charged. In such cases, in the examples provided herein, the separate electrodes count as and behave as a single electrode.

[0357] It can be appreciated that the component networks 111 and systems described herein can also be used with catheters designed for bipolar energy delivery. Thus, the PEF energy described herein can be delivered to target tissue using a bipolar energy delivery catheter used in a monopolar fashion. In such cases, one of the electrodes on the bipolar energy delivery catheter is utilized as the delivery electrode, and the remaining electrodes are considered additional electrodes (i.e., secondary, tertiary, quaternary, etc.). Thus, component networks 111 or systems based on the same principles described above can be used with bipolar energy delivery catheters. Examples of bipolar energy delivery catheters are provided by Farapulse (Menlo Park, CA), Affera Inc. (Watertown, MA), Atrian Medical (Galaway, Ireland), and Kardium Inc. (Burnaby, BC, Canada), to name a few.

[0358] It can be understood that the component networks 111 and systems described herein can be used with any high voltage energy, including radio frequency irreversible electroporation, pulsed radio frequency ablation, nanosecond pulsed electric fields, etc. Examples of other high voltage energies are described in U.S. Publication No. 2019 / 0201089, filed December 20, 2018, entitled METHODS, APPARATUSES, AND SYSTEMS FOR THE TREATMENT OF PULMONARY DISORDERS, WO2019 / 133606, filed December 26, 2018, entitled METHODS, APPARATUSES, AND SYSTEMS FOR THE TREATMENT OF DISEASE STATES AND DISORDERS, and WO2019 / 133608, filed December 26, 2018, entitled OPTIMIZATION OF ENERGY DELIVERY FOR VARIOUS APPLICATIONS, to name a few.

[0359] It should be understood that references herein to a treatment catheter typically apply to a specialized catheter 102 configured to deliver the PEF energy described herein, or a conventional catheter 101, with the use of one or more accessories, that is adapted to deliver the PEF energy described herein. Typically, such a treatment catheter will be referred to as a treatment catheter 102 for ease of reading, but it can be understood that such a description applies to the treatment catheter 101 in many or all cases.

[0360] tissue lesions When treating various cardiac conditions, different patients encounter different target tissue thicknesses. Therefore, tissue lesions of different depths may be desirable. In some embodiments, a highly reproducible, well-defined, and monotonic trend in lesion size results from dose intensity for single-parameter manipulation. Thus, in some embodiments, changing a single parameter of energy proportionally changes the resulting lesion size. However, it can be appreciated that the correlation between delivered energy and lesion depth may vary depending on various conditions, such as the size, shape, and configuration of the electrode placement, along with the parameter values ​​and energy waveform characteristics, to name a few. Thus, in some embodiments, the correlation is nonlinear but follows a curve. For a given condition, a variety of optimally titrated doses may be available (e.g., via algorithm 152) to treat a range of expected target tissue thicknesses in a patient. Aspects considered to determine the final dose range include the cross-sectional width and depth of the target tissue, the risk of air bubble formation, the desired duration of treatment delivery, potential temperature rise, preservation of ECG waveform and rhythm, safety to phrenic nerve and esophageal tissue, and the qualitative safety of the resulting treatment effect to the heart itself.

[0361] Example dosages and resulting effects are summarized in Table 3. [Table 3]

[0362] FIG. 18 provides a schematic diagram of a treatment catheter 102 positioned for pulmonary vein isolation. In particular, FIG. 18 illustrates a cross-section of the lumen L of the pulmonary vein PV, surrounded by cardiac tissue CT and then the surrounding body tissue BT. In this illustration, the diameter of the lumen L is 25 mm, and the thickness of the cardiac tissue CT is 4 mm. The treatment catheter 102 is shown with a delivery electrode 122 at its distal end, which is illustrated contacting the cardiac tissue CT through the lumen L. In this embodiment, the electrode 122 delivers energy in a monopolar manner, with energy flowing outward from the electrode 122 toward 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 of varying depth depending on the energy delivery algorithm 152. In this example, a treatment region A penetrating a thickness of 4 mm is achieved. It can be appreciated that, typically, as energy increases, the size of the treatment region A increases as well. An example of the relationship between energy and treatment depth is illustrated in the graph (sloped line) of FIG. 19, which shows that a 4 mm lesion can be achieved with an energy output of approximately 1.5 joules. This is achieved using the focal catheter and energy waveform-generating algorithm 152 illustrated in FIG. 18, as shown below. It can be appreciated that lesion depths greater than 4 mm, such as 5 mm, 6 mm, 7 mm, 8 mm, 9 mm, 10 mm, and greater, can be achieved with the devices and methods provided herein. FIG. 19 also illustrates the relationship between energy and thermal effects, which is a flat line across the x-axis. In this manner, the delivered energy is non-thermal. As previously mentioned, the therapeutic energy delivered via the delivery electrodes 122 is generally characterized by high-voltage pulses that enable removal of targeted tissue with little or no disruption of critical anatomical structures, such as tissue-level structural proteins within the extracellular matrix. This prevents dangerous collateral effects such as stenosis and thrombus formation.

[0363] The specific characteristics of the devices and energy waveforms provided herein provide excellent lesion depth to energy usage correlation. Therefore, the devices and systems described herein can deliver deeper lesions using less energy than other known PEF devices using known PEF energies. Less energy results in lower thermal effects and reduced demands on the generator. In some embodiments, this is a result of the nature of the current distribution. By delivering energy in a monopolar manner, the energy can penetrate deeper into cardiac tissue CT than if the energy were delivered in a bipolar manner. In a monopolar manner, the current passes directly through the tissue to a remote return electrode, extending deep into the myocardium. This contrasts with bipolar pair electrodes, where the energy only travels shallowly into the tissue and returns to the end effector with the return electrode. Therefore, the energy does not travel as deeply. The current follows the path of least resistance, being directed across the tissue, but not much current penetrates deep into the tissue. Therefore, bipolar electrode placement requires a much more aggressive treatment protocol to reach deeper treatment depths in the target tissue. This characteristic becomes more pronounced as the target depth increases further (i.e., to reach 2mm to 4mm, approximately 4 times the energy may be required, whereas extending the treatment depth from 2mm to 6mm with this design may 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, usually accompanied by various negative side effects such as excessive heating.

[0364] While monopolar PEF energy can penetrate tissue more deeply than bipolar PEF or RF, it can be appreciated that nearby critical structures are protected from damage due to the nature of PEF energy and the presence of different tissue planes in cardiovascular anatomy. In particular, the pericardial fluid and pericardium surrounding the heart act to dissipate energy and protect extracardiac structures, such as the esophagus, phrenic nerve, coronary arteries, lungs, and bronchi, from damage. This is not the case when delivering energy that creates lesions through thermal injury. In these cases, conductive thermal energy propagation beyond the targeted myocardial tissue can result in thermal damage to non-targeted extracardiac structures. Figures 20 and 21 illustrate, through mathematical modeling, the current distribution of PEF energy emitted from the delivery electrode 122 of the catheter 102 under various conditions (as illustrated in Figure 13). Here, the delivery electrode 122 is positioned within the heart near the pericardium PC and beyond, such as the esophagus E. Figure 20 shows the current density distribution when all tissues are considered homogeneous. Thus, the energy beam is shown radiating unimpeded from the delivery electrode 122 directly into the surrounding tissue. However, FIG. 21 illustrates the current density distribution when the tissue is heterogeneous, taking into account differences in tissue types across different anatomical structures. As illustrated, the energy beam is shown directed toward the pericardium PC, where it dissipates along the pericardium PC. As a result, the energy reaching beyond the pericardium PC is dramatically reduced and insignificant to the surrounding tissue, including the esophagus E. FIG. 22 provides a graph of current density versus penetration depth in homogeneous versus heterogeneous tissue. The first curve, H, corresponds to homogeneous tissue, and the current density decreases with increasing tissue depth, following a continuous asymptotic curve. The second curve, N-H, corresponds to heterogeneous tissue, as modeled in FIG. 21, illustrating the varying current density at various depths as the tissue type changes.

[0365] It should be appreciated that a variety of different types of lesions can be created using the treatment catheter 102 described herein. As previously described, lesion rings, such as those around the ostia of pulmonary veins, can be created using either a focal catheter or a one-shot catheter. Additionally, a focal catheter can be used to create many other types of lesions, particularly lines along various surfaces of cardiac tissue. In one embodiment, a cavotricupsial line is created for the treatment of typical atrial flutter in the right atrium. In another embodiment, a roof and / or floor line is created for a box lesion along the posterior wall of the left atrium for patients with atrial fibrillation, particularly persistent atrial fibrillation. In another embodiment, a mitral isthmus line is created along the anterior or lateral wall of the left atrium for atypical atrial flutter. In yet another embodiment, a ventricular line is created to connect two non-excitable boundaries important in the initiation or maintenance of reentrant ventricular arrhythmias, typically in patients with ventricular tachycardia due to ischemic heart disease.

[0366] Contact and Contact Force In some embodiments, contact and contact force are assessed to evaluate engagement and ensure uniform contact between the electrode and tissue. Such assessments are not provided in known PEF devices and systems utilized for treating cardiac tissue, such as treating atrial fibrillation. It has been argued that PEF energy delivery depends solely on the proximity of the electrode to the target tissue, rather than on contact. The effects of PEF energy on tissue are believed to be proximity-dependent, but not contact-dependent, as they are the result of the electric field extending from the electrode. The effects are believed to be a function of the voltage delivered and the distance over which the voltage is applied. Thus, the effects at any location within the tissue depend on the electric field strength.

[0367] However, these known PEF devices and systems rely on bipolar energy delivery, which generates an electric field around the electrode. In contrast, the devices, systems, and methods described herein are primarily used monopolarly, driving the electric field into the tissue toward a remote return electrode. Without contact, surrounding blood flow dissipates, disrupting energy flow and reducing tissue penetration. Therefore, improved engagement increases the delivery of PEF energy to the tissue. Similarly, uniform engagement optimizes such delivery.

[0368] Figures 23A and 23B show the effect of contact force on lesion size, specifically lesion width and depth. Three levels of contact force 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 contact force has a beneficial effect on both lesion size and depth. As shown in Figure 23A, 28 amperes of PEF energy as described herein were delivered to ventricular tissue in a monopolar configuration for 1.4 milliseconds, resulting in lesion depths of approximately 4 mm to 8 mm. Lesion depth correlated with contact force, with increasing contact force resulting in increased lesion depth. As shown in Figure 23B, 35 amperes of PEF energy as described herein were delivered to ventricular tissue in a monopolar configuration for 1.6 milliseconds, resulting in similar lesion depths of approximately 4 mm to 8 mm. Again, lesion depth correlated with contact force, with increasing contact force resulting in increased lesion depth.

[0369] In some embodiments, the therapeutic catheters described herein include mechanisms for measuring contact and / or contact force. In some embodiments, contact is sensed using an impedance sensor, specifically the impedance between the tip of the catheter 102 and the cardiac tissue. Impedance is expressed as a complex number derived from resistance and reactance. In some embodiments, impedance is desired to be measured by sensing impedance characteristics between electrodes on a focal catheter, between an electrode on the catheter and a separate, remote electrode located remotely elsewhere in the body or heart, between an electrode on the catheter and multiple separate electrodes located remotely elsewhere in the body or heart, or by a similar combination of dedicated impedance sensors located along the tip of the catheter or the shaft of an electrode where it is desired to determine the presence of electrode contact.

[0370] In other embodiments, contact force is sensed. This can be accomplished by several mechanisms, generalized as the contact force sensor 815 illustrated in FIG. 25. In some embodiments, contact force is measured by detecting changes in specific wavelengths of light reflected by a fiber Bragg grating (FBG). In some embodiments, the contact force sensor 815 includes an optical sensor with at least one optical fiber attached near the distal end of the catheter 102, which is deformable. Light is provided through the 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, compressing or stretching the at least one optical fiber, changing the periodic period of the R refractive index pattern. This change in period shifts the wavelength of the reflected light in proportion to the applied force. Thus, the direction and magnitude of the force are sensed. In some embodiments, the sum and magnitude of the axial and lateral component vectors of the contact force are provided to the user. In other embodiments, contact force is measured by compressing or stretching a spring. In such embodiments, the contact force sensor 815 comprises a small spring attached to the distal end of the catheter 102. The degree of compression and / or extension of the spring is detected at specific time intervals by at least one receiving sensor located at the base of the spring. The measured contact force values ​​are then provided to the user. In some embodiments, the real-time values ​​(e.g., direction, force, etc.) are provided in graphical form or any suitable format.

[0371] Temperature Sensing and Control The tissue modification system 100 described herein delivers a series of PEF batches or bundles described herein over a period of time, such as several seconds. This accumulation of energy deposition results in a small amount of Joule heating, inherent to all PEF therapies, as it is a by-product of energy deposition. While acute, subacute, intermediate, and long-term histological data all indicate virtually no signs of thermal damage to tissue using the systems, devices, and methods described herein, the temperature changes resulting from the delivery of PEF energy described herein were specifically evaluated. This evaluation was performed by monitoring the output from a thermocouple embedded in the distal electrode tip of the catheter electrode using a handheld digital multimeter (Klein Tools, MM700). Video recording of the multimeter readings was used to track the evolution of the catheter electrode's temperature change during delivery. A treatment dose designed to achieve a 6.6 mm treatment depth was delivered to the left atrium at a cadence representing a patient heart rate of 119 bpm. The resulting thermal profile of the catheter electrode is provided in Figure 24. Here, we observe that even in high-dose situations, temperatures never exceed 45°C, well below the threshold for the rapid onset of extracellular protein denaturation (65°C). Note that temperatures also return to within 1°C of baseline by approximately 5 seconds after reaching peak temperature. Therefore, it is clear that no thermal damage (extracellular protein denaturation) occurs in cardiac tissue, reducing the likelihood of treatment-related adverse events and anatomical defects such as pulmonary vein stenosis. This also eliminates the creation of surface char or thermal damage that would interfere with energy delivery to underlying tissue, reducing the ability to generate transmural lesions.

[0372] However, it can be appreciated that in some embodiments, system 100 includes temperature sensing and / or control means for various purposes. In some embodiments, temperature is sensed and controlled to remain within the range of 30-65°C, 30-60°C, 30-55°C, 30-50°C, 30-45°C, or 30-35°C. Thus, lesions are not created by thermal burns because the tissue temperature remains below the thermal ablation threshold. In some embodiments, temperature sensors are used to measure electrode and / or tissue temperature during treatment to ensure that the energy being deposited in the tissue does not cause clinically significant tissue heating. For example, the temperature sensors can monitor the temperature of the tissue and / or electrodes, and if a predefined threshold temperature (e.g., 65°C) is exceeded, the generator can modify its algorithm to automatically stop energy delivery or to reduce the temperature below the predefined threshold. For example, in some embodiments, if the temperature exceeds 65°C, the generator reduces the temperature by decreasing the pulse width or increasing the time between pulses and / or packets (e.g., delivering energy every other heartbeat, every third heartbeat, etc.). This can occur in a predefined, stepwise approach, as a percentage of a parameter, or in other manners. It will be appreciated that the temperature sensor is positioned on the electrode (as illustrated in FIG. 25), adjacent to the electrode, or in any suitable location along the distal portion of the catheter 102. Alternatively, or additionally, the sensor may be positioned on one or more separate devices.

[0373] In other embodiments, temperature is sensed to assess lesion formation. This can be particularly useful when creating lesions in anatomical structures with target tissue regions of different thicknesses. A sudden increase in temperature indicates that the lesion has penetrated deep into the tissue and is nearing completion. Sensing such temperature changes can be particularly useful when creating lesions in thicker tissue or tissue of unknown depth.

[0374] In some embodiments, the treatment catheter 102 includes irrigation to help control the temperature of the delivery electrode 122 or surrounding tissue. In some cases, the irrigation cools the delivery electrode 122, allowing for more PEF delivery per time period without increasing potential heat-mediated damage. In some cases, the irrigation also reduces or prevents clotting near the tip of the catheter 102. It may be appreciated that irrigation may be activated, increased, decreased, or stopped based on information from one or more sensors, particularly one or more temperature sensors.

[0375] Such cooling is achieved by delivering a fluid, such as an isotonic saline solution, through the lumen of the catheter 102, exiting through one or more irrigation ports along the distal end of the catheter 102. The fluid can be chilled, room temperature, or warmed. Fluid flow can be driven by a variety of mechanisms, including gravity-driven drip, peristaltic pumps, centrifugal pumps, and the like. In some embodiments, irrigation has a flow rate of 0.1 to 10 ml / min, including 1 ml / min, 2 ml / min, 3 ml / min, 4 ml / min, 5 ml / min, or more. 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, and in other embodiments, the temperature of the fluid is altered, such as to be heated or cooled, as it is pumped into the treatment catheter 102 based on the measured temperature. In some embodiments, the flow rate of the fluid is determined based on the measured temperature of the tissue being treated.

[0376] In some embodiments, the pump is in electrical communication with the generator 108, and the fluid flow rate is varied by the generator 108 based on the status of energy delivery to the therapy catheter 102. For example, in some embodiments, the fluid flow rate is increased during energy delivery. Similarly, in some embodiments, the fluid flow rate is increased until a predetermined time before energy delivery and / or at a predetermined time during energy delivery. Alternatively, or additionally, the fluid flow may be controlled on demand by the user. It may be appreciated that the pump may communicate with the generator 108 to operate at different speeds based on various aspects of the energy delivery algorithm 152. In some embodiments, flow rate sensing and communication with the generator 108 is used to prevent energy delivery when irrigation is not being performed. In other embodiments, the selection of the energy delivery algorithm 152, in turn, selects a fluid flow rate appropriate for the energy delivery algorithm 152.

[0377] In some embodiments, at least one irrigation port is located along the electrode and / or optionally, at least one irrigation port is located along the shaft 120. In some embodiments, as shown in FIG. 25 , the treatment catheter 102 includes a delivery electrode 122 having a cylindrical “solid tip” configuration. In some embodiments, one or more irrigation ports 822 are located along the distal surface of the cylindrical electrode tip. This allows for fluid delivery directly from the distal tip of the catheter 102. In some embodiments, one or more irrigation ports 822′ are located along the side of the cylindrical-shaped delivery electrode 122. In some embodiments, one or more irrigation ports 822″ are located along the edge of the cylindrical-shaped 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 then outside of the delivery electrode 122. It can be appreciated that the irrigation port 822 can be located in multiple locations, including proximally along the shaft 120.

[0378] In some embodiments, irrigation also mitigates the effects of macro- and microbubble formation. Gas embolism is a concern with many PEF therapies, particularly due to the potential for the generation of small "microbubbles" at the delivery electrode 122. Studies have shown that as little as 0.1 mL of air in a coronary artery can cause myocardial injury. Small bubbles are thought to dissolve more easily back into the bloodstream, while larger bubbles are more likely to embolize, potentially leading to an ischemic event. Microbubbles typically form on the surface of the electrode and grow in size as more energy is delivered. When microbubbles become large enough, they float away from the electrode. Irrigation at the electrode creates a flow of solution that removes bubbles when they are small, allowing them to dissolve more easily before reaching the coronary arteries. Therefore, the irrigation port 822, which allows fluid to flow over the exterior of the delivery electrode 122, specifically aids in reducing microbubble formation.

[0379] Interface Connector Conventional electroanatomical mapping (EAM) systems are often used to provide real-time, three-dimensional anatomical information to guide conventional catheter ablation procedures without the drawbacks of radiation exposure or a fluoroscopy room. EAM systems typically use magnetic-based or impedance-based mapping algorithms, or a combination of both, to visualize and generate models and maps (e.g., the CARTO® system by Biosense Webster / Johnson & Johnson and the EnSite™ system by St. Jude Medical / Abbott). Using these systems, electrophysiologists create real-time, 3D representations of cardiac anatomy and electrical activity by positioning a mapping catheter in various regions of the heart. As the physician moves the catheter in a sweeping motion, the system tracks the catheter's position. During the procedure, the table on which the patient lies contains a magnetic frame that generates a magnetic field that tracks the catheter's movement via magnetic sensors in the catheter. Additionally, a patch on the patient's skin emits an electrical current that allows the system to track impedance changes at the catheter's electrodes. Another EAM system, the KODEX-EPD system (Philips), has been introduced, which includes a novel approach to cardiac imaging that demonstrates real-time HD imaging providing true anatomy and produces voltage and activation maps.

[0380] Electroanatomical mapping systems are sometimes referred to as multimodality mapping or image integration systems because they can display images and data from other sources. For example, a patient's computed tomography (CT) or magnetic resonance imaging (MRI) scans taken days or weeks before the procedure can be loaded into EnSite™ or CARTO® and matched with a real-time 3D model of the heart. 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 several common areas of the two images are identified, the system merges / fuse the 3D model with the CT / MRI scan into a single 3D model. This process typically takes approximately 15 minutes to complete, but it can take longer if the position of anatomical structures can change within just a week, so if the pre-procedure scans do not easily correspond with the real-time view of the heart.

[0381] Electroanatomical mapping systems also provide real-time data on electrical activity within the heart, allowing the electrophysiologist to confirm that conduction block has been achieved. In some cases, the system can provide other real-time information, such as atrial pressure and cardiac volumes, to monitor the patient during the procedure.

[0382] Thus, electroanatomical mapping systems perform at least three important functions: (a) non-fluorescent localization of electrophysiological catheters in three-dimensional space, (b) analysis and 3D display of activation sequences calculated from local or computed electrograms, and (c) integration of this "electroanatomical" information with non-invasive imaging of the heart, such as computed tomography or magnetic resonance imaging.

[0383] In some embodiments, during electrophysiology (EP) procedures in which pulsed field energy is utilized as the treatment energy, the electrodes of the treatment catheter are used for multiple purposes. For example, in some embodiments, in addition to delivering PEF energy, the electrodes are used to measure low-voltage intracardiac electrograms and / or measure impedance in an electroanatomical mapping system. To do this, the electrodes of the cardiac treatment catheter are simultaneously connected to a pulsed field generator and several EP devices (e.g., an EP recording system, an electroanatomical mapping system such as CARTO®, EnSite™, or KODEX-EPD). If these systems share the same electrical conductors, the signals of the various devices may interfere with each other.

[0384] An interface connector is provided that minimizes interference between various devices connected to the contacts (e.g., electrodes, sensors, etc., of a cardiac treatment catheter). The interface connector includes a switching system so that the EP signal amplifier (e.g., an EP recording system and an electroanatomical mapping system such as CARTO®, Ensite™, or KODEX-EPD) is isolated when PEF energy is being delivered through the catheter. In some embodiments, such isolation is achieved using a high-voltage relay. When PEF energy is not being delivered through the catheter, the PEF generator is similarly isolated from the EP signal amplifier, such as by using a high-voltage relay.

[0385] FIG. 26 shows an example setup in which the interface connector 10 is utilized with an embodiment of a tissue modification system 100. In this embodiment, the tissue modification system includes a specialized catheter 102 (however, a conventional catheter 101 delivering PEF energy could alternatively be used), a high-voltage biphasic waveform generator 108, and at least one separate energy delivery algorithm 152. It can be appreciated that additional accessories and equipment can be utilized, such as an external cardiac monitor 110 connected to external electrodes 172 applied to the patient P to acquire an ECG. In this embodiment, the treatment catheter 102 is designed to be monopolar, with the distal end of the catheter 102 having at least one delivery electrode and a return electrode 106 positioned on the skin outside the body, typically on the thigh, lower back, or back. In this embodiment, the heart is accessed via the right femoral vein FV by a suitable access procedure, such as the Seldinger technique. Typically, an introducer sheath 112 is inserted into the femoral vein FV, which serves as a conduit through which various catheters and / or tools, including the treatment catheter 102, can be advanced. As shown in Figure 26, the distal end of the 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 entrance to the pulmonary veins. In this embodiment, the catheter 102 is used to perform cardiac mapping, which refers to the process of identifying the temporal and spatial distribution of myocardial electrical potentials during a specific cardiac rhythm. Cardiac mapping during arrhythmia aims to elucidate the mechanism of the cardiac rhythm, describe the propagation of activation from initiation to completion within a region of interest, and identify sites of origin or critical conduction that can serve as targets for therapy. Once the desired treatment location is identified, the catheter 102 is utilized to deliver the therapeutic energy.

[0386] In some embodiments, the proximal end of the treatment catheter 102 is electrically connected to an interface connector 10. In the embodiment illustrated in FIG. 26, the interface connector 10 is electrically connected to a waveform generator 108 and a separate external device 12, such as one capable of providing electroanatomical mapping procedures (e.g., the CARTO® system, the Ensite™ system, the KODEX-EPD system, etc.). Additionally, as shown in this embodiment, the generator 108 is connected to an external cardiac monitor 110 to enable coordinated delivery of energy with cardiac signals being sensed from the patient P.

[0387] It may be understood that in some cases, the interface connector 10 is connected directly to an electroanatomical mapping system, such as the patient interface unit of the electroanatomical mapping system, using a cable. However, it may be understood that in other embodiments, the interface connector 10 is connected to a pin box, breakout box, input / output box, junction box, or other accessory connected to the electroanatomical mapping system by a dedicated cable. The dedicated cable spreads the multi-cable lines into individual component connectors or chip pins that can be inserted into receptacles in the pin box. This allows individual access to each electrode. The pin box is then connected to the electroanatomical mapping system. It may also be understood that the interface connector 10 may include pin box features to eliminate a separate pin box. Thus, the interface connector 10 may include a receptacle for receiving chip pins and associated electronics.

[0388] 27 or 28 illustrate an embodiment of an interface connector 10 having a switching system 13. 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 the distal tip of the catheter. 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 conductor line or trace path 30 and a branch path 32. The first port 20 is connected to the second port 22 by the conductor line or trace path 30. The branch path 32 of the conductor line or trace branches off from the path of electrical wiring 30 and connects to the third port 24. Each pathway 30, 32 includes at least one switch 36, 38, where opening the switch 36, 38 prevents the passage of a signal therethrough and closing the switch 36, 38 allows the signal to pass therethrough. Thus, the passage of signals between ports 20, 22, 24 can be controlled by selectively opening and closing the switches 36, 38. For example, FIG. 27 shows switch 36 in path 30 closed, thereby allowing input signals (e.g., EP mapping signals or intracardiac electrogram signals) from electrodes 122, 125 to connect catheter 102 to a separate external device 12, while switch 38 in pathway 32 is open to prevent the passage of electrical signals from generator 108 to electrodes 122, 125. 28 illustrates switch 38 in pathway 32 closed, thereby delivering therapeutic energy from generator 108 (connected to port 24) to electrodes 122, 125, while switch 36 in pathway 30 is open to prevent the passage of electrical signals to separate external device 12 (connected to port 22). In certain embodiments, each of switches 36, 38 is implemented using a respective high voltage relay.

[0389] 27 or 28, the catheter 102 is shown as having four electrodes 122, 125, but alternatively, the catheter 102 may have more or fewer than four electrodes. Here, each of the ports 20, 23, and 24 includes a separate electrical terminal corresponding to each of the electrodes 122, 125, with each terminal providing an electrical connection between one of the electrodes 122, 125 and one of the conductive lines or traces within each of the pathways 30, 32. Similarly, each of the pathways 30, 32 includes a separate conductive line or trace and a separate switch 36, 38 corresponding to each of the electrodes 122, 125. All of the switches 36 within the pathway 30 may be simultaneously opened or closed. Alternatively, one or more of the switches 36 within the pathway 30 may be open, while one or more other of the switches 36 are closed, such that only one of the electrodes 122, 125 is used to sense the input signal. Similarly, all of the switches 38 within the pathway 33 may be simultaneously opened or closed. Alternatively, one or more switches 38 in pathway 32 can be open, while one or more other of the switches 38 are closed, and only a particular one of the electrodes 122, 125 is used to deliver therapeutic energy.

[0390] 28, if second port 22 (e.g., electrically connected to an EP signal amplifier) ​​is switched during PEF energy delivery, the electrophysiologist will not be able to visualize the position of catheter 102 and see the intracardiac electrogram signal. Therefore, it is typically desirable to switch out second port 22 (e.g., electrically connected to an EP signal amplifier) ​​for a short period of time during which a portion of the energy is delivered (e.g., as a "packet").

[0391] Therapeutic energy delivery can be activated by various mechanisms, such as using a button on the catheter 102 or a footswitch operably connected to the generator 108. Such activation typically provides a single energy dose. The energy dose may be defined, at least in part, by the number of packets delivered and the voltage of the packets. The energy dose may also be defined, but is not limited to, by the number of pulses in each packet and the pulse width of each pulse within each packet. In some embodiments, such therapeutic energy delivery is synchronized with the heartbeat of the patient P, such as by synchronizing packet delivery using an R-wave trigger from the cardiac monitor 110. In some embodiments, the switching of paths 30, 32, or relays is controlled based on an "AND" logic of the generator footswitch signal and the cardiac monitor's R-wave trigger signal, as illustrated in FIG. 29. The high-voltage relay and EP signal amplifier, configured to deliver PEF energy, can be isolated only when both the footswitch and the R-wave trigger signal are enabled. In certain embodiments, the R-wave trigger signal is enabled with a programmable delay following each detection of an R-wave in the sensed intracardiac electrogram. In all other logic states of the footswitch and R-wave trigger, the high voltage relay is configured to not deliver energy and the generator 108 is isolated from all mapping signals and intracardiac electrograms by opening the switch 38, which is implemented as a relay.

[0392] In some embodiments, the switching system 13 utilizes signal filtering rather than switches to achieve its intended function. This typically depends on the frequency range of the various signals. For example, FIG. 30 illustrates an embodiment of the connector 10 that is suitable when the frequency of the signal between the 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 reject high-frequency PEF energy. Similarly, the signal line between the catheter 102 and the generator 108 includes a high-pass filter 42 to reject all low-frequency signals used by the electroanatomical mapping system and EP recording system.

[0393] In some cases, it may be desirable for the catheter 102 to communicate with the generator 108 to deliver PEF energy while communicating with a separate external device 12, such as to monitor contact force. If the catheter 102 is not configured for this situation, portions of the catheter 102 (e.g., one or more electrodes, internal wiring, etc.) may overheat or fail. This may be mitigated by various design features. In some embodiments, the interface connector 10 is adapted to control the passage of signals in coordination with PEF energy delivery. For example, in some embodiments, the catheter 102 is used for impedance sensing, ECG sensing, contact force sensing, and magnetic force, to name a few. In such embodiments, some features may be used simultaneously without deleterious effects. In some cases, impedance sensing and ECG sensing may be utilized with limited or no interference or adverse effects with PEF delivery. Thus, in some embodiments, certain signals may be allowed to pass during the delivery of PEF energy. This may be achieved by operating the appropriate switches 36, 38. In this example, the switches 36, 38 along the paths of the conductive lines or traces associated with impedance sensing and ECG sensing are both open. In some embodiments, certain signals are likely to interfere with or cause adverse effects on PEF delivery, such as signals related to contact force sensing and magnetic force. In such embodiments, these signals may be blocked during PEF energy delivery. This may be accomplished by operating appropriate switches 36, 38. In this example, one or more of the switches 36 in the path 30 along the conductive lines or traces related to contact force sensing and / or magnetic force are closed during PEF energy delivery and open otherwise. Similarly, one or more switches 38 in the path 32 along these conductive lines or traces are open during PEF energy delivery and closed otherwise. It may be understood that any combination of functions may be allowed or blocked at any time, either by operation of the switches 36, 38 or by alternative design.It may also be appreciated that, due to the nature of PEF delivery, such interruption of access to the electroanatomical mapping system may be so brief that it may not be noticeable to the user. For example, contact force sensing and / or imaging may appear continuous to the user concurrently with these interruption periods. It should be appreciated that in other embodiments, one or more signals may be manipulated to enable the catheter 102 to electrically communicate with the generator 108 and a separate external device 12 simultaneously.

[0394] Alternatively, as shown in FIG. 31 , signals unrelated to energy delivery or cardiac mapping may travel along paths separate from paths 30, 32. For example, signals related to contact and / or contact force sensing may travel along a path of conductive lines or traces 50 that is separate from paths 30, 32 involved in switching between generator 108 and external device 12. Here, contact and / or contact force sensing traces 50 extend from port 20 to port 23, which in turn connects to module 54 having components related to measuring contact and / or contact force. This separates activities related to sensing contact and / or contact force from energy delivery, mapping, etc. Similarly, signals related to temperature sensing may travel along a path of conductive lines or traces 52 that is also separate from paths 30, 32 involved in switching between generator 108 and external device 12. Here, temperature sensing trace 52 extends from port 20 to port 23, which connects to module 54 (or optionally a separate module) having components related to measuring temperature, thereby separating activities related to temperature sensing from energy delivery, mapping, etc.

[0395] In some embodiments, particularly when utilizing a conventional ablation catheter 101, a component network 111 is included in the interface connector 10 as shown in FIG. 32 or 33. FIG. 32 illustrates an embodiment of the interface connector 10 similar to FIG. 31 with the addition of component network 111. Here, component network 111 is disposed between switching system 13 and port 24, which connects to generator 108. This configuration can be used when connecting catheter 102 to separate devices for mapping and sensing (e.g., contact force sensing, temperature sensing, etc.). Thus, switching system 13 is disposed between port 20 and port 22. This may be particularly true when external device 12 includes an Ensite™ electroanatomical mapping system and module 54 includes a Tactisys™ system, which provides components for contact force and temperature monitoring. Similarly, FIG. 33 illustrates component network 111 disposed between switching system 13 and port 24, which connects to generator 108. However, this configuration can be used when connecting catheter 102 to a single device that provides mapping and sensing (e.g., contact force sensing, temperature sensing, etc.). In this case, switching system 13 is again positioned between ports 20 and 22, but port 23 is omitted so that contact and / or contact force sensing traces 50 and temperature sensing traces 52 extend from port 20 to port 22. This may be particularly true if external device 12 includes a CARTO® electroanatomical mapping system that includes components for contact force and temperature monitoring.

[0396] FIG. 34 shows an embodiment of a tissue modification system 100 for use with a patient (not shown) that includes a treatment catheter (either a specialized catheter 102 or a 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., capable of providing an electroanatomical mapping procedure), an external cardiac monitor 110, and various other accessories, including a pin box 171. FIG. 35 illustrates an embodiment of a tissue modification system 100 for use with a patient P in which the treatment catheter includes a particular conventional RF catheter 101, a Tacticath™ 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 an electroanatomical mapping procedure), an external cardiac monitor 110, and various other accessories, including a pin box 171. In addition, system 100 includes a module 54 that includes a Tactisys™ system for contact force and temperature acquisition.

[0397] System 100 produces therapeutic effects that are readily apparent in real time while monitoring the delivery and progression of the treatment. In some cases, strong attenuation of the ECG signal is evident in the treatment catheter after delivery of the treatment. Additionally, in some embodiments, voltage mapping is performed before and after single-site treatment, and changes in the voltage maps are evident, confirming operation with a 3D mapping system and the ability to use them to track delivery progression as treatment sites are connected, creating a continuous lesion of electrical conduction block.

[0398] Alternative Therapeutic Catheter Design The systems and devices described herein can alternatively be used with various other types and styles of treatment catheters 102. In some embodiments, the treatment catheter 102 is designed to deliver a localized therapy, while in other embodiments, the treatment catheter 102 is designed to deliver a "one-shot" therapy. Localized therapy is considered to be a therapy in which energy is delivered sequentially, such as repeatedly applying energy point-by-point around a pulmonary vein to create a circular treatment zone, as previously illustrated in FIG. 4. One-shot therapy is considered to be a therapy in which energy is delivered via a delivery electrode to the entire circumference of the entrance to the pulmonary vein in a "one shot," although such delivery may be repeated as needed. This may optionally include rotation of the electrode 122 between "shots," as needed.

[0399] focal therapy As previously mentioned, focal therapy is typically performed using a delivery electrode 122 having a cylindrical shape with a distal face, as shown in FIG. 2A or 2B. In some embodiments, the distal face 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 the distal face is positioned against the tissue, the surface contact area is approximately 7 mm. 2 When delivering PEF energy as described here, with the following parameter values, 3300V / 400kHz / 40 cycles / 30 packets, 3300V / 400kHz / 30 cycles / 10 packets, and 2000V / 400kHz / 40 cycles / 30 packets, each packet of energy delivers 15 joules of energy. In these cases, the current density at the delivery electrode is approximately 2mm 2 is.

[0400] It will be appreciated that local therapy may be delivered using alternative catheter designs and methods. For example, in some embodiments, the treatment catheter 102 is configured to provide focal therapy in accordance with International Patent Application No. PCT / US2018 / 067504, entitled "OPTIMIZATION OF ENERGY DELIVERY 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, all of which are incorporated herein by reference for all purposes.

[0401] One-shot therapy 36 illustrates an embodiment of a treatment catheter 102 configured to deliver a "one-shot" therapy. One-shot therapy is considered to be therapy in which energy is delivered in a "one shot" through a delivery electrode to an entire treatment area, such as around the ostium of a pulmonary vein, although such delivery can be repeated as needed. This can optionally include rotation of the electrodes 122 between "shots," as needed.

[0402] In this embodiment, the catheter 102 comprises an elongated shaft 120 having a delivery electrode 122 near its distal end 124 and a handle 126 near its proximal end 128. Here, the delivery electrode 122 is configured to deliver energy to a wider area, such as the entire treatment region, particularly to create a continuous treatment area around a pulmonary vein to block conduction. In this embodiment, the delivery electrode 622 has a distal-facing cup or funnel shape. The footprint created by the delivery electrode 622 has a larger diameter than the footprint created by a focal therapy catheter. This is to achieve a specific treatment with a single application. Thus, while in some embodiments, treatment is provided with a single application of the electrode 122 to the tissue, it can be understood that in some cases, energy can be applied multiple times as needed. The handle 126 is used to operate the catheter 102, particularly to steer the distal end 124 during delivery and treatment. Energy is provided to the catheter 102, and thus the delivery electrode 122, via a cable 130 connectable to the generator 108.

[0403] 37A and 37B show a similar embodiment of a delivery electrode 122 configured to deliver a "one-shot" therapy, where the delivery electrode 122 has a cup or funnel shape. In this embodiment, the electrode 122 includes multiple wires 140 forming an expandable half-basket, with at least one of the wires functioning as a 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., free end). Thus, in the expanded configuration, the half-basket shape has a rim 146 that forms a circular shape along its distal end 144. In this embodiment, the wires 140 are curved along the rim 146 to create an atraumatic surface. FIG. 37B provides an end view of the embodiment of FIG. 37A. As illustrated, the rim 146 is circular, and the remainder of the half-basket has a woven appearance as it funnels down the shaft 120. It can be appreciated that the multiple wires 140 can be woven or intertwined in various configurations. It may also be understood that the delivery electrode 122 may be self-expanding, where the electrode 122 exists in a collapsed configuration while maintained within the sheath and self-expands to an expanded configuration upon removal of the sheath. Alternatively, it may also be understood that the delivery electrode 122 may alternatively be expanded by other mechanisms, such as by inflation of a delivery balloon.

[0404] Figures 38A and 38B illustrate application of the delivery electrode 122 of Figures 37A and 37B to a surface, such as a region of cardiac tissue. In these illustrations, the electrode 622 is shown contacting a benchtop, demonstrating its shape change during application of increasing contact force. It can be seen that a similar shape change occurs upon contact with tissue, particularly cardiac tissue surrounding a pulmonary vein. The circular opening of the pulmonary vein can be visualized and aligned within the circular shape of the rim 146 so that the delivery electrode 122 contacts the tissue surrounding the opening of the pulmonary vein. Figure 38A illustrates the electrode 122 positioned against a surface so that the rim 146 contacts the surface. Here, the electrode 122 substantially maintains its free state, having a funnel shape. Figure 38B illustrates the electrode 122 with increased pressure against the surface, causing portions of the conductive wire 140 to collapse together, forming a larger rim 146. Thus, the energy delivered by the plurality of conductive wires 140 increases along the rim 146 during application of pressure or contact force, due to an increase in the conductive wires 140 at least along the rim 146, compared to when minimal pressure or contact force is applied. FIG. 38B shows a condition where near maximum pressure or contact force is applied, and it can be seen that the half-basket has nearly completely collapsed, creating a short funnel shape. It can be seen that various different levels of pressure or contact force can be applied to various configurations of the half-basket shape between these two configurations (i.e., FIGS. 38A and 38B).

[0405] In some embodiments, at least a portion of one of the plurality of conductive wires is insulated from neighboring conductive wires of the plurality of conductive wires. In some embodiments, at least a portion of one of the plurality of conductive wires is insulated, leaving exposed portions of the conductive wire to create an active region that focuses energy at a specific location along the target tissue. In some embodiments, the plurality of conductive wires can be energized simultaneously. In other embodiments, at least some of the plurality of conductive wires can be energized individually. In some embodiments, the delivery electrode 122 includes an insulator covering at least a portion of the plurality of conductive wires 140. For example, FIG. 39 shows an embodiment of the delivery electrode 122, as in FIGS. 38A and 38B , in which a portion of the plurality of conductive wires 140 is covered with an insulator 150. In this embodiment, the insulator 150 substantially covers the portion of the half-basket shape that does not collapse, or minimally collapses, into the rim 146 upon application of force against the tissue. Thus, the insulator 150 covers a portion of the proximal end 142 of the delivery electrode 122. This allows more energy to be delivered towards the distal end 144 of the delivery electrode 122 , particularly the rim 146 , as the energy is not dissipated into the environment through the proximal end 142 .

[0406] FIG. 40A provides a schematic diagram of a cross section of the lumen L of the pulmonary vein PV surrounded by cardiac tissue CT and then surrounding body tissue BT. In this illustration, the diameter of the lumen L is 25 mm, and the thickness of the cardiac tissue is 4 mm. A treatment catheter 102 is shown having a delivery electrode 122 at its distal end, with the electrode 122 shown contacting the cardiac tissue CT simultaneously at various locations through the lumen L. In this example, it can be seen that the delivery electrode 122 has a full basket shape and is inserted into the lumen L. However, in other embodiments, it can be visualized that a half-basket shape could be inserted into the lumen L, or that the rim 146 could be positioned relative to the tissue surrounding the lumen L.

[0407] In this embodiment, the catheter 102 delivers energy in a monopolar manner, with energy flowing outward from the delivery electrode 122 toward 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 of varying depth depending on the energy delivery algorithm 152. In this example, a treatment region A penetrating a thickness of 4 mm is achieved. It can be seen that typically, as energy increases, the size of the treatment region A increases as well. An example of the relationship between energy and treatment region depth is illustrated in the graph of FIG. 40B (sloping line). FIG. 40B also illustrates the relationship between energy and thermal effect, which is a flat line across the x-axis. Thus, the delivered energy is non-thermal.

[0408] Another type of delivery electrode 122 configured to deliver a "one-shot" therapy has a loop shape. Typically, the loop shape comprises one or more loops arranged to form a continuous circular rim. FIG. 41 shows an embodiment of a delivery electrode 122 comprising an initial single loop. In this embodiment, the electrode 122 is formed from a shape-memory wire 160 that can be twisted and folded back on itself during delivery to create a substantially circular rim 162. Thus, through the folding action, the initial single loop forms a secondary loop 165 that extends around the rim 162, such that the circular rim 162 is substantially comprised of two layers of wire 160. In this embodiment, the secondary loop 165 extends around nearly the entire circumference of the rim 162 (i.e., the initial loop and the secondary loop 165 together form the rim 162), and thus more than half of the circumference of the rim 162 is comprised of two layers of wire. The circular rim 162, when deployed as illustrated below, is typically substantially perpendicular to the shaft 120 when deployed as illustrated in FIG. 42 , providing a profile of the delivery electrode 122 as illustrated in FIG. 41 . This allows the rim 162 to be positioned relative to the cardiac tissue surrounding the entrance to the pulmonary vein. Energy is thus delivered to the entire circumference of the entrance to the pulmonary vein via the delivery electrode 122 in a “one shot,” although such delivery may be repeated as needed. This may optionally include rotation of the electrode 122 between “shots,” as needed. In this embodiment, the shaft 120 is offset and not concentric with the circular rim 162, although it will be appreciated that in other embodiments, the shaft 120 is concentric with the rim 162.

[0409] 43A-43E illustrate the deployment of the delivery electrode 122 of FIGS. 41 and 42. In this embodiment, the delivery electrode 122 is configured to be housed within the shaft 120; however, it can be appreciated that, alternatively, a sheath can be advanced over the catheter 102 to capture the electrode 122. Initially, the electrode 122 is deployed and flattened into a relatively straight configuration when housed within the shaft 120. This allows the electrode 122 to collapse into a small configuration, thereby enabling a small outer diameter shaft 120 for advancement through the vasculature. In this embodiment, the electrode 122 is deployed by advancement of the electrode 122 from the shaft 120. FIG. 43A illustrates the electrode 122 advancing from the distal end of the shaft 120 and initially having a straight configuration. This is the first loop. It can be appreciated that the deployment steps illustrated in FIGS. 43A-43E are still images from a video in which each step occurs in rapid succession on its own. Thus, upon release, the electrode 122 self-configures into its deployed configuration. FIG. 43B illustrates the electrode 122 beginning to fold downward on itself, revealing its loop shape. In this embodiment, the distal-most portion 170 of the loop curves and curls back proximally toward the shaft 120. FIG. 43C shows the distal-most portion 170 bending further downward so that the loop forms a V-shape. This V-shape is an early stage in the formation of two layers of conductive wire that create the rim 162. FIG. 43D illustrates the transformation of the electrode 122 from a V-shape into a double-layered loop. This step occurs so quickly that it cannot be visualized with the naked eye. In this embodiment, the V-shaped portions cross each other in a twisting and folding manner to form a double loop from a single loop. FIG. 43E shows the final configuration of the electrode 122 in its fully deployed state. Here, the loop of conductive wire 160 forms a circular rim 162, substantially composed of two layers of conductive wire 160. As shown, the circular rim 162 is normally substantially perpendicular to the shaft 120 when deployed.

[0410] 44A-44B illustrate another embodiment of a delivery electrode 122 including a loop of shape memory wire 160 that creates a substantially circular rim 162. In this embodiment, as illustrated in FIG. 44A, two loops 165a, 165b overlap, and together they form the circular rim 162. In FIG. 44B, the two loops 165a, 165b are separated for visualization. In this embodiment, each of the two loops 165a, 165b forms an arc 167 that traverses approximately 270 degrees of a circle around the shaft 120. Thus, the circular rim 162 consists of two layers of conductive wire 160, with the loops 165a, 165b overlapping. In this embodiment, the overlapping area extends approximately halfway around the rim 162 (each loop 165a, 165b extends approximately one-quarter of the way around the opposing portion of the circumference of the rim 162). Thus, approximately half of the circumference of the rim 162 is comprised of two layers of conductive wire. However, it can be understood that the loops 165a, 165b can be configured to cover different portions of the circumference of the rim 162, including nearly the complete rim. The circular rim 162 is typically substantially perpendicular to the shaft 120 when deployed, as illustrated in FIG. 45, which provides a side view of the delivery electrode 122 shown in FIG. 44A. This allows the rim 162 to be positioned relative to the cardiac tissue surrounding the entrance to the pulmonary vein. Energy is thus delivered to the entire circumference of the entrance to the pulmonary vein through the delivery electrode 122 in a "one shot," although such delivery may be repeated as needed. This may optionally include rotating the electrode 122 between "shots," as needed. In this embodiment, the shaft 120 is offset and not concentric with the circular rim 162, but it can be understood that in other embodiments, the shaft 120 is concentric with the circular rim 162.

[0411] FIG. 46A shows another embodiment of a delivery electrode 122 including loops of shape-memory conductive wire 160 that come together to form a substantially circular rim 162. In this embodiment, the electrode 122 is comprised of three loops 165a, 165b, and 165c that extend at least partially around the rim 162, such that the circular rim 162 is comprised of two layers of three-part conductive wire 160. In FIG. 46B, the three loops 165a, 165b, and 165c are separated for visualization. In this embodiment, each of the three loops 165a, 165b, and 165c forms an arc 167 that traverses approximately 270 degrees of a circle around the shaft 120. Thus, the circular rim 162 is comprised of three layers of three-part conductive wire 160 with overlapping loops 165a, 165b, and 165c. In this embodiment, the overlapping region extends approximately the entire circumference of the rim 162. In this embodiment (each loop 165a, 165b, 165c extends around approximately one-third of the circumference of the rim 162). Thus, nearly the entire circumference of the rim 162 is comprised of two layers of conductive wire. The circular rim 162 is typically substantially perpendicular to the shaft 120 when deployed, as illustrated in FIG. 47, providing the side of the delivery electrode 122 shown in FIG. 46A. This allows the rim 162 to be positioned relative to the cardiac tissue surrounding the entrance to the pulmonary vein. Thus, energy is delivered to the entire circumference of the entrance to the pulmonary vein via the delivery electrode 122 in a "one shot," although such delivery may be repeated as needed. This may optionally include rotating the electrode 122 between "shots," as needed. While in this embodiment, the shaft 120 is offset and not concentric with the circular rim 162, it can be understood that in other embodiments, the shaft 120 is concentric with the rim 162.

[0412] The above detailed description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, 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 in addition to those shown or described. However, the inventors also contemplate examples in which only the elements shown or described are provided. Furthermore, the inventors also contemplate examples (or one or more aspects thereof) that use any combination or permutation of those elements shown or described with respect to a particular example (or one or more aspects thereof), or with respect to any other example (or one or more aspects thereof) shown or described herein.

[0413] In the event of inconsistent usage between this document and a document incorporated by reference, the usage in this document shall prevail.

[0414] In this document, the terms "a" or "an" are used to include one or more, as is common in patent documents, regardless of other instances or uses of "at least one" or "one or more." In this document, the term "or" is used to refer to a non-exclusive or "A or B" inclusive "A is not B," "B is not A," or "A and B," unless otherwise specified. In this document, the terms "comprises" and "in which" are used as the plain English equivalents of the respective terms "comprising" and "wherein." Also, in the following claims, the terms "comprising" and "comprising" are used open-ended, i.e., system, device, article, composition, formulation, or process claims that include elements in addition to those listed after the following terms are still considered to be within the scope of those claims. Furthermore, in the following claims, terms such as "first," "second," and "third" are used merely as labels and are not intended to impose numerical requirements on their objects.

[0415] The above description is illustrative and not limiting. For example, the above examples (or one or more aspects thereof) can be used in combination with each other. Other embodiments may be utilized, such as would occur to one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to comply with 37 CFR §1.72(b) to enable the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Additionally, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be construed as intending that unclaimed disclosed features are essential to a claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Accordingly, the following claims are incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it is contemplated that such embodiments can be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full range of equivalents to which such claims are entitled.

Claims

1. 1. A system for treating cardiac tissue of a patient, comprising: a treatment catheter having a delivery electrode; a generator electrically coupleable to the treatment catheter, the generator including at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through the delivery electrodes; The system, wherein the treatment catheter and the generator together are configured to monopolarly deliver the pulsed electric field energy through the cardiac tissue to a remote return electrode.

2. The system of claim 1 , wherein the delivery electrode is cylindrical and has a distal surface configured to be positioned against the cardiac tissue.

3. The system of claim 2 , wherein the distal face comprises a single continuous surface.

4. 10. The system of claim 1, wherein the delivery electrode comprises a distal face having a contact surface configured to be positioned against the cardiac tissue.

5. The system of claim 4, wherein the contact surface has a circular shape with a diameter of 2 to 3 mm.

6. The contact surface is 3 to 8 mm ２ 5. The system of claim 4 having a surface area of

7. 10. A system according to any one of the preceding claims, wherein the electrical signal comprises packets of biphasic pulses.

8. 10. The system of claim 1, wherein the generator is configured to receive a measurement of a depth of the cardiac tissue and to select one of the at least one energy delivery algorithm based on the measurement of the depth.

9. 10. The system of any one of the preceding claims, wherein the generator is configured to receive a measurement of the cardiac tissue depth and to select one of the at least one energy delivery algorithm that provides energy that is expected to create a non-thermal lesion having a depth that exceeds the measurement of the cardiac tissue depth.

10. 10. The system of any one of the preceding claims, wherein the generator is configured to receive at least one measure of heart rate in beats per minute, and wherein the generator is configured to cease energy delivery if the at least one measure of heart rate in beats per minute is below a predetermined threshold.

11. 10. The system of any one of the preceding claims, wherein the generator is configured to receive at least one measure of heart rate in beats per minute, and wherein the generator is configured to provide less frequent energy delivery if the at least one measure of heart rate in beats per minute is greater than or equal to a predetermined threshold.

12. 12. The system of claim 11, wherein the less frequent frequency comprises every other heartbeat.

13. 10. The system of any one of the preceding claims, further comprising a temperature sensor, the generator configured to modify energy delivery based on at least one measurement from the temperature sensor.

14. The system of claim 13 , wherein modifying energy delivery comprises providing energy delivery less frequently when the at least one measurement from the temperature sensor is at or above a predetermined threshold.

15. 15. The system of claim 14, wherein the less frequent frequency comprises every other heartbeat.

16. 16. The system of claim 14 or 15, wherein the predetermined threshold is 65°C.

17. 17. The system of claim 13, wherein the treatment catheter further comprises at least one irrigation port, and the system further comprises an irrigation pump, the irrigation pump configured to vary delivery of irrigation fluid therethrough based on the at least one measurement from the temperature sensor.

18. 10. The system of any one of the preceding claims, further comprising a contact or force sensor, wherein the generator is configured to modify at least one of the at least one energy delivery algorithm based on at least one measurement from the contact or force sensor.

19. 1. A system for creating a lesion in a region of cardiac tissue of a patient, comprising: a treatment catheter having a delivery electrode; a generator electrically coupleable to the treatment catheter, the generator including at least one energy delivery algorithm configured to provide an electrical signal of pulsed electric field energy deliverable through the delivery electrodes to create the lesion in the cardiac tissue, the lesion being of sufficient depth to block electrical signals passing through a region of the cardiac tissue.

20. 20. The system of claim 19, wherein the electrical signal comprises a series of biphasic pulses.

21. 21. The system of claim 20, wherein the series of biphasic pulses is delivered in multiple packets.

22. 22. The system of claim 21, wherein each packet of the plurality of packets comprises between 30 and 45 biphasic pulses.

23. 23. The system of claim 21 or 22, wherein the multiple packets are delivered in multiple bundles, each bundle being delivered during a predetermined portion of each heartbeat.

24. 24. The system of claim 23, wherein the predetermined portion comprises a T wave.

25. The system of claim 23 or 24, wherein each bundle contains 1 to 3 packets.

26. 26. The system of claim 25, wherein 10 to 30 packets are delivered to create the lesion.

27. 1. A catheter for treating a region of cardiac tissue, comprising: a shaft having a longitudinal axis; a delivery electrode having a conductive rim extending about the longitudinal axis, the continuous rim having a closed shape configured to engage an opening of a pulmonary vein to create a continuous lesion around the opening of the pulmonary vein.

28. 1. A subsystem for use with a catheter configured to be connected to a signal generator, the catheter comprising: a catheter body including a distal portion and a proximal portion, the distal portion of the catheter body comprising a plurality of electrodes electrically insulated from one another, the proximal portion of the catheter body comprising a plurality of terminals and configured to be connected to a signal generator, thereby allowing stimulation energy to be delivered through selected one or more of the electrodes, the catheter also comprising a plurality of conductive wires each electrically coupling a different one of the electrodes to a respective different one of the terminals, the subsystem comprising: a subsystem comprising a network of components configured to maintain a potential difference between the one or more of the electrodes of the catheter selected to deliver stimulation energy and one or more other electrodes of the catheter not selected to deliver stimulation energy below a threshold potential difference that prevents arcing between one or more pairs of the conductive wires.

29. 1. A system for adapting a catheter having a plurality of electrodes electrically isolated from one another, at least one of the plurality of electrodes being selectable for delivery of stimulation energy, the catheter including a plurality of conductive wires each electrically coupled to a different one of the electrodes, the system comprising: A system comprising: a component network configured to increase a current threshold for arcing between one or more pairs of the conductive lines.

30. 30. The system of claim 29, wherein the component network comprises a plurality of resistors.

31. 31. The system of claim 30, wherein each of the plurality of resistors is disposed between a conductive line electrically coupled to an electrode selected to deliver stimulation energy and a conductive line electrically coupled to an electrode not selected to deliver stimulation energy.

32. 30. The system of claim 29, wherein the component network comprises at least one resistor, inductor, or diode.

33. 33. The system of claim 32, wherein a value of at least one of the at least one resistor, inductor, or diode is selectable.

34. 34. The system of claim 33, further comprising an algorithm that determines the at least one value based on information provided by a user.

35. 34. The system of claim 33, further comprising an algorithm comprising a three-dimensional mathematical model of the current distribution from the catheter.

36. The system of any one of claims 29 to 35, wherein the catheter comprises a radiofrequency ablation catheter or a microwave catheter.

37. 37. The system of any one of claims 29 to 36, wherein the stimulation energy comprises pulsed electric field energy.

38. 1. A system for adapting a catheter that at least partially fails when receiving stimulation energy having a voltage or current above a threshold level, comprising: A system comprising: a component network coupleable to the catheter, the component network increasing the threshold level to a higher threshold level.

39. 40. The system of claim 38, wherein the catheter comprises a dielectric material and the at least partial failure comprises a breakdown of the dielectric material.

40. 40. The system of claim 38 or 39, wherein the catheter is configured to receive stimulation energy including radiofrequency or microwave energy, and the network of components adapts the catheter to receive stimulation energy including high-voltage energy.

41. 41. The system of claim 40, wherein the high voltage energy comprises pulsed electric field energy, irreversible electroporation energy, pulsed radiofrequency ablation, or nanosecond pulsed electric field energy.

42. 42. The system of any one of claims 38-41, wherein the catheter at least partially fails when it receives stimulation energy having a voltage or current above a threshold level due to arcing between one or more pairs of conductive wires, and wherein the network of components prevents arcing between the one or more pairs of conductive wires when it receives stimulation energy having a voltage or current above the threshold level and below the higher threshold level.

43. 1. A system comprising: a catheter having a delivery electrode, the catheter configured to deliver thermal ablation energy; a generator electrically coupleable to the treatment catheter, the generator including at least one energy delivery algorithm configured to provide an electrical signal of non-thermal high-voltage energy deliverable through the delivery electrode.

44. 44. The system of claim 43, wherein the thermal ablation energy comprises radiofrequency ablation energy or microwave ablation energy.

45. 45. The system of claim 43 or 44, wherein the high voltage energy comprises pulsed electric field energy.

46. 46. ​​The system of any one of claims 43 to 45, wherein the high voltage energy comprises an electrical signal having packets of biphasic pulses.

47. 47. The system of any one of claims 43 to 46, wherein the treatment catheter and the generator together are configured to deliver the high voltage energy monopolarly through tissue to a remote return electrode.

48. 48. The system of any one of claims 43 to 47, wherein the high voltage energy has a voltage of at least 2000V.

49. 45. The system of claim 43 or 44, wherein the high voltage energy comprises irreversible electroporation energy, pulsed radiofrequency ablation, or nanosecond pulsed electric field energy.

50. 1. A system for treating cardiac tissue of a patient, comprising: a treatment catheter having at least one contact point; a generator electrically coupleable to the treatment catheter, the generator including 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 contact; an interface connector that electrically couples the at least one contact to both the generator and an electroanatomical mapping system, the interface connector preventing the at least one contact from simultaneously electrically communicating with both the generator and the electroanatomical mapping system.

51. 51. The system of claim 50, wherein the interface connector comprises a switching system including a first pathway of at least one conductive line between the at least one contact and the generator and a second pathway of at least one conductive line between the at least one contact and the electroanatomical mapping system, the switching system toggling the energy transfer between the first pathway and the second pathway.

52. 52. The system of claim 50 or 51, wherein at least one of the at least one contact senses an input signal, the input signal comprising a cardiac mapping signal or a cardiac electrogram.

53. 53. The system of any one of claims 50-52, wherein the at least one contact comprises a plurality of electrodes electrically isolated from one another, at least one of the plurality of electrodes being selectable for delivery of stimulation energy.

54. 54. The system of claim 53, wherein the catheter comprises a plurality of conductive wires each electrically coupled to a different one of the plurality of electrodes, and the interface connector further comprises a component network configured to increase a current threshold for arcing between one or more pairs of conductive wires.

55. 56. The system of any one of claims 50 to 55, wherein the at least one contact comprises a thermocouple electrically coupleable to the electroanatomical mapping system.

56. 56. The system of any one of claims 50 to 55, wherein the at least one contact comprises a thermocouple electrically coupleable to a module comprising a component for temperature monitoring.

57. 57. The system of claim 56, wherein the thermocouple is in electrical communication with the module independent of communication between the catheter and the generator or between the catheter and the electroanatomical mapping system.

58. 58. The system of any one of claims 50 to 57, wherein the at least one contact comprises a contact or force sensor electrically coupleable to the electroanatomical mapping system.

59. 59. The system of any one of claims 50 to 58, wherein the treatment catheter is configured to deliver the pulsed electric field energy in a monopolar manner.

60. An interface connector, a first port for electrically connecting a catheter having at least one contact, the first port including a separate electrical terminal corresponding to each of the at least one contact; a second port for electrically connecting a generator to one or more of the at least one contact for delivering high voltage energy through the generator and the contact; a third port for electrically connecting an external device to one or more of the at least one contacts to transfer low voltage energy between the external device and the contacts; and a switching system comprising: a first path of at least one conductive line connecting the first port to the second port; and a second path of at least one conductive line connecting the first port to the third port, wherein the switching system toggles the energy transfer between the first path and the second path.

61. 61. The interface connector of claim 60, wherein the high voltage energy comprises pulsed electric field energy.

62. 62. The interface connector of claim 60 or 61, wherein the high voltage energy has a voltage of at least 1000 volts.

63. 63. The interface connector of any one of claims 60 to 62, wherein the low voltage energy has a voltage of less than 500 volts.

64. 64. The interface connector of any one of claims 60-63, wherein the second port electrically connects the generator to two or more of the at least one contact to deliver high voltage energy through the generator and the contacts, and wherein the interface connector further comprises a passive component network disposed along the first path, the passive component network modulating the energy delivered to the two or more of the at least one contact to prevent failure of the catheter.

65. 64. The interface connector of any one of claims 60-63, wherein the second port electrically connects the generator to two or more of the at least one contact to deliver high voltage energy through the generator and the contacts, and the interface connector further comprises a passive component network disposed along the first path, the passive component network increasing a current threshold for arcing between one or more pairs of conductive wires comprising the catheter connected to the two or more of the at least one contact.

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