DEVICES FOR THE DELIVERY OF PULSED ELECTRIC FIELDS IN THE TREATMENT OF CARDIAC TISSUE

Devices, systems and methods are provided for treating conditions of the heart, particularly the occurrence of arrhythmias, more particularly atrial fibrillation, atrial flutter, ventricular tachycardia, to name a few. The devices, systems and methods deliver therapeutic pulsed electric field energy to portions the heart to provide tissue modification, such as to the entrances to the pulmonary veins in the treatment of atrial fibrillation. Such tissue modification creates a conduction block within the tissue to prevent the transmission of aberrant electrical signals. Generally, the tissue modification systems include a specialized catheter, a high voltage waveform generator and at least one distinct energy delivery algorithm. Example embodiments of specialized catheter designs are provided and include a variety of delivery types including focal delivery, “one-shot” delivery and various possible combinations.

BACKGROUND

Therapeutic energy can be applied to the heart and vasculature for the treatment of a variety of conditions, including atherosclerosis (particularly in the prevention of restenosis following angioplasty) and arrhythmias, such as atrial fibrillation. Atrial fibrillation is the most common sustained cardiac arrhythmia, and severely increases the risk of mortality in affected patients, particularly by causing stroke. In this phenomenon, the heart is taken out of normal sinus rhythm due to the production of erroneous electrical impulses. Atrial fibrillation is thought to be initiated in the myocardial sleeves of the pulmonary veins (PVs) due to the presence of automaticity in 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 the maintenance of atrial fibrillation because the chaotic architecture and electrophysiological properties of these vessels provides an environment where atrial fibrillation can be perpetuated. Thus, destruction or removal of these aberrant pacemaker cells within the myocardial sleeves of the PVs has been a 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 been conventionally modified to one that targets PV antra to achieve conduction block between the PVs and the left atrium. The PV antra encompass, in addition to the pulmonary veins, the left atrial roof and posterior wall and, in the case of the right pulmonary vein antra, a portion of the interatrial septum. In some instances, this technique offers a higher success rate and a lower complication rate compared with pulmonary vein ostial isolation.

Thermal ablation therapies, especially radiofrequency (RF) ablation, are currently the “gold standard” to treat symptomatic atrial fibrillation by localized tissue necrosis. Typically, RF ablation is used to create a ring of ablation lesions around the outside of the ostium of each of the four pulmonary veins. RF current causes desiccation of tissue by creating a localized area of heat that results in discrete coagulation necrosis. The necrosed tissue acts as a conduction block thereby electrically isolating the veins.

Despite the improvements in reestablishing sinus rhythm using available methods, both success rate and safety are limited. RF ablation continues to present multiple limitations including long procedure times to perform pulmonary vein isolation with RF focal catheters, potential gaps in ablation patterns due to point-by-point ablation technique with conventional RF catheters, difficulty in creating and confirming transmural ablation lesions, char and/or gas formation at the catheter tip-tissue interface due to high temperatures, which may lead to thrombus or emboli during ablation, and thermal damage to collateral extracardiac structures, which include pulmonary vein stenosis, phrenic nerve injury, esophageal injury, atrio-esophageal fistula, peri-esophageal vagal injury, perforations, thromboembolic events, vascular complications, and acute coronary artery occlusion, to name a few. These limitations are primarily attributed to the continuous battle clinicians have faced balancing effective therapeutic dose with inappropriate energy delivery to extracardiac tissue.

Thus, while keeping the technique in clinical practice, safer and more versatile methods of removing abnormal tissue have been used, including irreversible electroporation (IRE), a non-thermal therapy based on the unrecoverable permeabilization of cell membranes caused by particular short pulses of high voltage energy. IRE has been found to be tissue-specific, triggering apoptosis rather than necrosis, and safer for the structures adjacent the myocardium. However, thus far, the success of these IRE methodologies has been heterogeneous. In some instances, the delivery of IRE energy has resulted in incomplete block of the aberrant electrical rhythms. This may be due to a variety of factors, such as irregularity of treatment circumferentially around the pulmonary veins, lack of transmural delivery of energy or other deficiencies in the delivery of energy. In either case, atrial fibrillation is not sufficiently treated or atrial fibrillation recurs at a later time. Therefore, improvements in atrial fibrillation treatment are desired. Such treatments should be safe, effective, and lead to reduced complications. At least some of these objectives will be met by the systems, devices and methods described herein.

SUMMARY

Described herein are embodiments of apparatuses, systems and methods for treating target tissue, particularly cardiac tissue. Likewise, the invention relates to the following numbered clauses:1. A device for delivering energy to cardiac tissue of a patient comprising:a shaft having a proximal end and a distal end, wherein the shaft has an outer diameter; andan energy delivery body disposed along the distal end of the shaft, wherein the energy delivery body is transitionable between a collapsed configuration and an expanded configuration, wherein the expanded configuration has an outer diameter that is less than or equal to 6 times the outer diameter of the shaft, wherein the energy delivery body is configured to be positioned against the cardiac tissue in the expanded configuration so as to deliver energy to the cardiac tissue.2. A device as in claim1, wherein the energy is pulsed electric field energy and wherein the device is configured to deliver the pulsed electric field energy to the cardiac tissue.3. A device as in any of the above claims, wherein the energy delivery body comprises a plurality of wires configured to deliver the energy.4. A device as in claim3, wherein the plurality of wires comprises a plurality of splines.5. A device as any of claims3-4, wherein the plurality of wires is comprised of shape memory material so that the energy delivery body is transitionable by release from a sheath that constrains the plurality of wires so that such release allows the plurality of wires to move toward the expanded configuration.6. A device as in claim5, wherein the energy delivery body is free of a central shaft when in the expanded configuration.7. A device as in claim5, wherein the plurality of splines form a hollow rounded cage.8. A device as in claim3, wherein the plurality of wires comprises a mesh.9. A device as in claim3, wherein the plurality of wires comprises a plurality of loops.10. A device as in any of claims3-9, wherein the plurality of wires is energizable in unison so as to function in a monopolar fashion.11. A device as in any of claims3-10, wherein the plurality of wires has a convex distal face.12. A device as in any of claims3-11, wherein the energy delivery body includes a distal tip configured to deliver the energy.13. A device as in claim12, wherein the distal tip and the plurality of wires are energizable in unison so as to function in a monopolar fashion.14. A device as in any of claims3-13, wherein a proximal portion of the plurality of wires is insulated so as to direct the energy toward a distal direction.15. A device as in any of the above claims, further comprising a plurality of irrigation ports, wherein the device is configured so as to direct fluid through the irrigation ports in a manner that creates turbulent flow of the fluid within the energy delivery body.16. A device as in claim15, wherein the plurality of irrigation ports are disposed near a proximal end of the energy delivery body.17. A device as in any of claims15-16, further comprising one or more irrigation lumens which direct the fluid through the plurality of irrigation ports.18. A device as in claim17, wherein the one or more irrigation lumens is less than the plurality of irrigation ports.19. A device as in any of the above claims, wherein the expanded configuration has an outer diameter that is 3-6 times the outer diameter of the shaft.20. A device as in any of the above claims, wherein the expanded configuration has an outer diameter that is 8-15 mm.21. A device as in any of the above claims, wherein the energy delivery body includes a sensing electrode.22. A device as in claim21, wherein the sensing electrode is positioned so as to avoid contact with the cardiac tissue.23. A device as in claim22, wherein the energy delivery body comprises a plurality of splines forming a rounded cage and wherein the sensing electrode is disposed within the rounded cage.24. A device as in any of the above claims, wherein the shaft includes one or more ring electrodes.25. A device as in any of the above claims, further comprising one or more electrodes that communicate with an electrophysiological mapping system.26. A device as in any of the above claims, further comprising a steering mechanism configured to bend the energy delivery body in relation to the shaft.27. A device as in any of the above claims, further comprising a steering mechanism configured to bend the distal end of the shaft away from its longitudinal axis.28. A device for treating cardiac tissue of a patient comprising:a shaft having a proximal end and a distal end; andan energy delivery body disposed along the distal end of the shaft, wherein the energy delivery body is configured to be positioned against the cardiac tissue, and wherein the energy delivery body is electrically couplable with a generator so as to deliver pulsed electric field energy to the cardiac tissue.29. A catheter as in claim28, wherein the energy delivery body comprises one or more loops shaped from wire.30. A catheter as in any of claims28-29, wherein the at least one electrode comprises one or more loops arranged to form a continuous rim that is configured to contact the cardiac tissue.31. A catheter as in claim30, wherein the continuous rim has a closed shape having a diameter of 8-15 mm.32. A catheter as in claim30, wherein the continuous rim has a closed shape having a diameter smaller than an internal diameter of a pulmonary vein.33. A catheter as in claim30, wherein the continuous rim has a closed shape configured to mate with an opening of a pulmonary vein so as to create a continuous lesion around the opening of the pulmonary vein.34. A catheter as in any of claims30-33, wherein the continuous rim forms a closed shape having an adjustable diameter.35. A catheter as in any of claims30-34, further comprising an electrode disposed along the distal end of the shaft so as to be able to contact the cardiac tissue when the continuous rim is positioned against the cardiac tissue and pressure is applied.36. A catheter as in claim35, wherein the electrode is disposed along the distal end of the shaft so as to disengage contact with the cardiac tissue when pressure is released from the continuous rim.37. A catheter as in any of claims28-36, wherein at least a portion of the energy delivery body is configured to at flex when the energy delivery body is positioned against the cardiac tissue pressure and pressure is applied.38. A catheter as in claim28, wherein the energy delivery body comprises one or more loops forming a convex distal face.39. A catheter as in claim38, wherein the convex distal face is configured to seat against an inlet of a pulmonary vein.40. A catheter as in claim39, wherein at least a portion of the convex distal face is configured to seat within the pulmonary vein.41. A catheter as in claim28, wherein the energy delivery body comprises one or more loops forming a concave distal face.42. A catheter as in claim41, wherein the one or more loops comprise two pairs of loops, wherein each pair of loops comprises a smaller loop within a larger loop.43. A catheter as in claim42, wherein the shaft has a longitudinal axis and wherein each of the two pairs of loops extend in opposite directions from the longitudinal axis.44. A catheter as in claim28, wherein the energy delivery body comprises a single paddle shaped electrode having a narrower shape near the shaft and a wider shape extending away from the shaft.

45. A catheter as in claim44, wherein the wider shape has a hammerhead shape.46. A catheter as in claim28, wherein the energy delivery body is transitionable between a collapsed configuration and an expanded configuration, wherein the expanded configuration has an outer diameter that is less than or equal to 6 times the outer diameter of the shaft, wherein the energy delivery body is configured to be positioned against the cardiac tissue in the expanded configuration so as to deliver energy to the cardiac tissue.47. A device for delivering energy to cardiac tissue of a patient comprising:a shaft having a proximal end and a distal end; andan energy delivery body disposed along the distal end of the shaft, wherein the energy delivery body is comprised of a plurality of shape-memory splines and is transitionable between a collapsed configuration and an expanded configuration, wherein in the expanded configuration the plurality of shape-memory splines form a convex distal face positionable against the cardiac tissue so as to deliver energy to the cardiac tissue.48. A device as in claim47, wherein the plurality of shape-memory splines form a rounded cage having the convex distal face in the expanded configuration.49. A device as in claim48, wherein the rounded cage is supported solely by the plurality of splines.50. A device as in claim49, wherein the energy delivery body includes a distal tip electrode and wherein the plurality of splines supports a tip electrode wire extending from the distal tip electrode to the shaft and is otherwise hollow.51. A device as in any of claims48-50, wherein the rounded cage is flexible so as to deform upon positioning against the cardiac tissue.52. A device as in any of claims48-51, wherein the rounded cage is flexible so as to at least partially flatten upon positioning against the cardiac tissue.53. A device as in any of claims48-52, wherein the convex distal face is configured to have a footprint of 8-15 mm when positioned against the cardiac tissue so as to deliver energy to the cardiac tissue.54. A device as in any of the above claims, wherein the plurality of splines are energizable in unison to function in a monopolar manner.55. A device as in any of the above claims, wherein the energy delivery body includes a distal tip electrode disposed along the convex distal face.56. A device as in claim55, wherein the distal tip electrode is independently energizable.57. A device as in any of the above claims, wherein at least a portion of the energy delivery body is insulated so as to direct the energy through the convex distal face.58. A device as in any of the above claims, further comprising at least one irrigation lumen and a plurality of irrigation ports.59. A device as in claim58, wherein the at least one irrigation lumen comprises a number of irrigation lumens that is less than plurality of irrigation ports.60. A device as in claim48, wherein the energy delivery body is electrically couplable with a generator so as to deliver pulsed electric field energy to the cardiac tissue.61. A system for delivering energy to cardiac tissue of a patient comprising:a treatment catheter comprisinga shaft having a proximal end and a distal end, wherein the shaft has an outer diameter, andan energy delivery body disposed along the distal end of the shaft, wherein the energy delivery body is transitionable between a collapsed configuration and an expanded configuration, wherein the expanded configuration has an outer diameter that is less than or equal to 6 times the outer diameter of the shaft, wherein the energy delivery body is configured to be positioned against the cardiac tissue in the expanded configuration so as to deliver energy to the cardiac tissue; anda generator electrically couplable to the treatment catheter, wherein the generator includes at least one energy delivery algorithm configured to provide an electric signal of pulsed electric field energy deliverable through the energy delivery body.62. A system as in claim61, wherein the pulsed electric field energy is below a threshold for inducing coagulative thermal damage.63. A system for treating cardiac tissue of a patient comprising:a treatment device comprisinga shaft having a proximal end and a distal end, andan energy delivery body disposed along the distal end of the shaft, wherein the energy delivery body is configured to be positioned against the cardiac tissue, and wherein the energy delivery body is electrically couplable with a generator so as to deliver pulsed electric field energy to the cardiac tissue; anda generator electrically couplable to the treatment catheter, wherein the generator includes at least one energy delivery algorithm configured to provide an electric signal of pulsed electric field energy deliverable through the energy delivery body.64. A system as in claim63, wherein the pulsed electric field energy is below a threshold for inducing coagulative thermal damage.65. A system for delivering energy to cardiac tissue of a patient comprising:a treatment catheter comprisinga shaft having a proximal end and a distal end, andan energy delivery body disposed along the distal end of the shaft, wherein the energy delivery body is comprised of a plurality of shape-memory splines and is transitionable between a collapsed configuration and an expanded configuration, wherein in the expanded configuration the plurality of shape-memory splines form a convex distal face positionable against the cardiac tissue so as to deliver energy to the cardiac tissue; anda generator electrically couplable to the treatment catheter, wherein the generator includes at least one energy delivery algorithm configured to provide an electric signal of pulsed electric field energy deliverable through the energy delivery body.66. A system as in claim65, wherein the pulsed electric field energy is below a threshold for inducing coagulative thermal damage.67. A method of treating a patient comprising:advancing a distal end of a catheter into a heart of the patient, wherein the catheter has an energy delivery body disposed along its distal end;positioning a return electrode remote from the distal end of the catheter;positioning at least a portion of the energy delivery body at a first location along an area of cardiac tissue;delivering pulsed electric field energy through the at least one electrode monopolarly so that the pulsed electric field energy is directed through the cardiac tissue to the return electrode; andrepeatedly re-positioning the at least a portion of the energy delivery body at one or more additional locations along the area of cardiac tissue so as to create a continuous lesion.68. A method as in claim67, wherein the first location and the one or more additional locations create a closed shape around a pulmonary vein of the heart.69. A method as in claim67, wherein the continuous lesion has a depth sufficient to block conduction between the pulmonary vein and a remainder of the heart.70. A method as in claim68, wherein the first location and the one or more additional locations create a linear shape having a depth sufficient to block conduction.71. A method as in claim67, wherein the energy delivery body comprises one or more loops arranged to form a continuous rim, and wherein positioning at least a portion of the energy delivery body comprises positioning the continuous rim.72. A method as in claim67, wherein the energy delivery body comprises one or more loops shaped from a wire.These and other embodiments are described in further detail in the following description related to the appended drawing figures.

INCORPORATION BY REFERENCE

DETAILED DESCRIPTION

Devices, systems and methods are provided for treating conditions of the heart, particularly the occurrence of arrhythmias, more particularly atrial fibrillation, atrial flutter, ventricular tachycardia, Wolff-Parkinson-White syndrome, and/or atrioventricular nodal reentry tachycardia, to name a few. The devices, systems and methods deliver therapeutic energy to portions the heart to provide tissue modification, such as to the entrances to the pulmonary veins in the treatment of atrial fibrillation. Targeted specific anatomic locations include the superior vena cava, inferior vena cava, right pulmonary vein, left pulmonary vein, right atrium, right atrial appendage, left atrium, left atrial appendage, right ventricle, left ventricle, right ventricular outflow tract, left ventricular outflow tract, ventricular septum, left ventricular summit, regions of myocardial scar, myocardial infarction border zones, myocardial infarction channels, ventricular endocardium, ventricular epicardium, papillary muscles and the Purkinje system, to name a few. Treatments are delivered at isolated sites or in a connected series of treatments. Types of treatment include the creation of left atrial roof line, left atrial posterior/inferior line, posterior wall isolation, lateral mitral isthmus line, septal mitral isthmus line, left atrial appendage, right sided cavotricuspid isthmus (CTI), pulmonary vein isolation, superior vena cava isolation, vein of Marshall, lesion creation using Complex Fractionated Atrial Electrograms (CFAE), lesion creation using Focal Impulse and Rotor Modulation (FIRM), and targeted ganglia ablation. Such tissue modification creates a conduction block within the tissue to prevent the transmission of aberrant electrical signals. The devices, systems and methods are typically used in an electrophysiology lab or controlled surgical suite equipped with fluoroscopy and advanced ECG recording and monitoring capability. An electrophysiologist (EP) is typically the intended primary user of the system. The electrophysiologist will be supported by a staff of trained nurses, technicians, and potentially other electrophysiologists. Generally, the tissue modification systems include a specialized catheter, a high voltage waveform generator and at least one distinct energy delivery algorithm. Additional accessories and equipment may be utilized. Example embodiments of specialized catheter designs are provided herein and include a variety of delivery types including focal delivery, “one-shot” delivery and various possible combinations. For illustration purposes a simplified design is provided when describing the overall system. Such a simplified design provides monopolar focal therapy. However, it may be appreciated that a variety of other embodiments are also provided.

FIG.1illustrates an embodiment of a tissue modification system100comprising a treatment catheter102, a mapping catheter104, a return electrode106, a waveform generator108and an external cardiac monitor110. 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 sheath112is inserted into the femoral vein FV which acts as a conduit through which various catheters and/or tools may be advanced, including the treatment catheter102and mapping catheter104. It may be appreciated that in some embodiments, the treatment catheter102and mapping catheter104are combined into a single device. As illustrated inFIG.1, the distal ends of the catheters102,104are advanced through the inferior vena cava, through the right atrium, through a transseptal puncture and into the left atrium so as to access the entrances to the pulmonary veins. The mapping catheter104is used to perform cardiac mapping which refers to the process of identifying the temporal and spatial distributions of myocardial electrical potentials during a particular heart rhythm. Cardiac mapping during an aberrant heart rhythm aims at elucidation of the mechanisms of the heart rhythm, description of the propagation of activation from its initiation to its completion within a region of interest, and identification of the site of origin or a critical site of conduction to serve as a target for treatment. Once the desired treatment locations are identified, the treatment catheter102is utilized to deliver the treatment energy.

In this embodiment, the proximal end of the treatment catheter102is electrically connected with the waveform generator108, wherein the generator108is software-controlled with regulated energy output that creates high frequency short duration energy delivered to the catheter102. It may 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 catheter104is also electrically connected with the waveform generator108and the electronics to perform the mapping procedure are included in the generator108. However, it may be appreciated that the mapping catheter104may alternatively be connected with a separate external device having the capability of providing the mapping procedure, such as electroanatomic mapping (EAM) systems (e.g. CARTO® systems by Biosense Webster/Johnson & Johnson, EnSite™ systems by St. Jude Medical/Abbott, KODEX-EPD system by Philips, Rhythmia HDX™ system by Boston Scientific). Likewise, in some embodiments, a separate mapping catheter104is not used and the mapping features are built into the catheter102.

In this embodiment, the generator108is connected with an external cardiac monitor110to allow coordinated delivery of energy with the cardiac signal 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 generator108when it detects the patient's cardiac cycle R-wave. This trigger signal, and the generator's algorithm, reliably synchronize the energy delivery with the patient's cardiac cycle to decrease the potential for arrhythmia due to energy delivery. Typically, a footswitch allows the user to initiate and control the delivery of the energy output. The generator user interface (UI) provides both audio and visual information to the user regarding energy delivery and the generator operating status.

In this embodiment, the treatment catheter102is designed to be monopolar, wherein the distal end of the catheter108has as a delivery electrode122and the return electrode106is positioned upon the skin outside the body, typically on the thigh, lower back or back.FIG.2Aillustrates an embodiment of a treatment catheter102configured to deliver focal therapy. In this embodiment, the catheter102comprises an elongate shaft120having a delivery electrode122near its distal end124and a handle126near its proximal end128. The delivery electrode122is shown as a “solid tip” electrode having a cylindrical shape with a distal face having a continuous surface. In some embodiments, the cylindrical shape has a diameter across its distal face of approximately 2-3 mm and a length along the shaft120of approximately lmm, 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. It may be appreciated that such electrodes are typically hollow yet are referred to as solid due to visual appearance. In some embodiments, the catheter102has an overall length of 50-150 cm, preferably 100-125 cm, more preferably 110-115 cm. Likewise, in some embodiments, it has a 7 Fr outer diameter 3-15 Fr, preferably 4-12 Fr, more preferably 7-8.5 Fr. It may be appreciated that in some embodiments, the shaft120has a deflectable end portion121and optionally the deflectable end portion121may have a length of 50-105 mm resulting in curves with diameters ranging from approximately 15 to 55 mm. Deflection may be achieved by a variety of mechanisms including a pull-wire which extends to the handle126. Thus, the handle126is used to manipulate the catheter102, particularly to steer the distal end124during delivery and treatment. Energy is provided to the catheter102, and therefore to the delivery electrode122, via a cable130that is connectable to the generator108.

Pulsed electric fields (PEFs) are provided by the generator108and delivered to the tissue through the delivery electrode122placed on or near the targeted tissue area. It may be appreciated that in some embodiments, the delivery electrode122is positioned in contact with a conductive substance which is likewise in contact with the targeted 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 treatment effectiveness both for the focal treatment as well as potential regional infiltration regions of the targeted tissue types. High voltage, short duration biphasic electric pulses are then delivered through the electrode122in the vicinity of the target tissue. These electric pulses are provided by at least one energy delivery algorithm152. In some embodiments, each energy delivery algorithm152prescribes a signal having a waveform comprising a series of energy packets wherein each energy packet comprises a series of high voltage pulses. In such embodiments, the algorithm152specifies parameters of the signal such as energy amplitude (e.g., voltage) and duration of applied energy, which is comprised of the number of packets, number of pulses within a packet, and the fundamental frequency of the pulse sequence, to name a few. Additional parameters may include switch time between polarities in biphasic pulses, dead time between biphasic cycles, and rest time between packets, which will be described in more detail in later sections. There may be a fixed rest period between packets, or packets may be gated to the cardiac cycle and are thus variable with the patient's heart rate. There may be a deliberate, varying rest period algorithm or no rest period may also be applied between packets. A feedback loop based on sensor information and an auto-shutoff specification, and/or the like, may be included.

It may be appreciated that in various embodiments the treatment catheter102includes a variety of specialized features. For example, in some embodiments, the catheter102includes a mechanism for real-time measurement of the contact force applied by the catheter tip to a patient's heart wall during a procedure. In some embodiments, this mechanism is included in the shaft120and comprises a tri-axial optical force sensor which utilizes white light interferometry. By monitoring and modifying the applied force throughout the procedure, the user is able to better control the catheter102so as to create more consistent and effective lesions.

In some embodiments, the catheter102includes one or more additional electrodes125(e.g. ring electrodes) positioned along the shaft120, such as illustrated inFIG.2B, proximal to the delivery electrode122. In some embodiments, some or all of the additional electrodes can be used for stimulating and recording (for electrophysiological mapping), so a separate cardiac mapping catheter is not needed when using catheter102for lesion creation, or for other purposes such as sensing, etc.

In some embodiments, the catheter102includes a thermocouple temperature sensor, optionally embedded in the delivery electrode122. Likewise, in some embodiments the catheter102includes a lumen which may be used for irrigation and/or suction. Typically, the lumen connects with one or more ports along the distal end of the catheter102, such as for the injection of isotonic saline solution to irrigate or for the removal of, for example, microbubbles.

In some embodiments, the catheter102includes 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 of the electrodes act 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 the therapy, monitor the therapy and/or provide direct feedback via the processor154, which can then alter the energy-delivery algorithm152. For example, impedance measurements can be used to determine not only the initial dose to be applied but can also be used to determine the need for further treatment, or not.

Referring back toFIG.1, in this embodiment the generator108includes a user interface150, one or more energy delivery algorithms152, a processor154, a data storage/retrieval unit156(such as a memory and/or database), and an energy-storage sub-system158which generates and stores the energy to be delivered. In some embodiments, one or more capacitors are used for energy storage/delivery, however any other suitable energy storage element may be used. In addition, one or more communication ports are included.

In some embodiments, the generator108includes three sub-systems: 1) a high-energy storage system, 2) a high-voltage, medium-frequency switching amplifier, and 3) the system controller, firmware, and user interface. In this embodiment, the system controller includes a cardiac synchronization trigger monitor that allows for synchronizing the pulsed energy output to the patient's cardiac rhythm. The generator takes in alternating current (AC) mains to power 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 is initiated. At the initiation of therapeutic energy delivery, the generator's controller, high-energy storage banks and a bi-phasic pulse amplifier can operate simultaneously to create a high-voltage, medium frequency output.

It will be appreciated that a multitude of generator electrical architectures may be employed to execute the energy delivery algorithms. In particular, in some embodiments, advanced switching systems are used which are capable of directing the pulsed electric field circuit to the energy delivering electrodes separately from the same energy storage and high voltage delivery system. Further, generators employed in advanced energy delivery algorithms employing rapidly varying pulse parameters (e.g., voltage, frequency, etc.) or multiple energy delivery electrodes may utilize modular energy storage and/or high voltage systems, facilitating highly customizable waveform and geographical pulse delivery paradigms. It should further be appreciated that the electrical architecture described herein above is for example only, and systems delivering pulsed electric fields may or may not include additional switching amplifier components.

The user interface150can include a touch screen and/or more traditional buttons to allow for the operator to enter patient data, select a treatment algorithm (e.g., energy delivery algorithm152), initiate energy delivery, view records stored on the storage/retrieval unit156, and/or otherwise communicate with the generator108.

In some embodiments, the user interface150is configured to receive operator-defined inputs. The operator-defined inputs can include a duration of energy delivery, 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 (but are not limited to): 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 any combination or subcombination thereof.

As mentioned, in some embodiments the system100also includes a mechanism for acquiring an electrocardiogram (ECG), such as an external cardiac monitor110, in situations wherein cardiac synchronization is desired. Example cardiac monitors are available from AccuSync Medical Research Corporation and Ivy Biomedical Systems, Inc. In some embodiments, the external cardiac monitor110is operatively connected to the generator108. The cardiac monitor110can be used to continuously acquire an ECG signal. External electrodes172may be applied to the patient P to acquire the ECG. The generator108analyzes one or more cardiac cycles and identifies the beginning of a time period during which 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 time period is within milliseconds of the R wave (of the ECG QRS complex) to avoid induction of an arrhythmia, which could occur if the energy pulse is delivered on a T wave. It will be appreciated that such cardiac synchronization is typically utilized when using monopolar energy delivery, however it may be utilized as part of other energy delivery methods.

In some embodiments, the processor154, among other activities, modifies and/or switches between the energy-delivery algorithms, monitors the energy delivery and any sensor data, and reacts to monitored data via a feedback loop. In some embodiments, the processor154is configured to execute one or more algorithms for running 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.

The data storage/retrieval unit156stores data, such as related to the treatments delivered, and can optionally be downloaded by connecting a device (e.g., a laptop or thumb drive) to a communication port. In some embodiments, the device has local software used to direct the download of information, such as, for example, instructions stored on the data storage/retrieval unit156and executable by the processor154. In some embodiments, the user interface150allows for the operator to select to download data to a device and/or system such as, but not limited to, a computer device, a tablet, a mobile device, a server, a workstation, a cloud computing apparatus/system, and/or the like. The communication ports, which can permit wired and/or wireless connectivity, can allow for data download, as just described but also for data upload such as uploading a custom algorithm or providing a software update.

As described herein, a variety of energy delivery algorithms152are programmable, or can be pre-programmed, into the generator108, such as stored in memory or data storage/retrieval unit156. Alternatively, energy delivery algorithms can be added into the data storage/retrieval unit to be executed by processor154. Each of these algorithms152may be executed by the processor154.

It may be appreciated that in some embodiments the system100includes an automated treatment delivery algorithm that dynamically responds and adjusts and/or terminates treatment in response to inputs such as temperature, impedance at various voltages or AC frequencies, treatment duration or other timing aspects of the energy delivery pulse, treatment power and/or system status.

As mentioned, in some embodiments, the cardiac monitor provides a trigger signal to the generator108when it detects the patient's cardiac cycle R-wave. This trigger signal, and the generator's algorithm, reliably synchronize the energy delivery with the patient's cardiac cycle to decrease the potential for arrhythmia due to energy delivery. This trigger is within milliseconds of the peak of the R wave (of the ECG QRS complex) to avoid induction of an arrhythmia, which could occur if the energy pulse is delivered on a T wave, and also to ensure that energy delivery occurs at a consistent phase of cardiac contraction. It will be appreciated that such cardiac synchronization is typically utilized when using monopolar energy delivery, however it may be utilized as part of other energy delivery methods.

In this embodiment, the generator108is connected with an external cardiac monitor110to allow coordinated delivery of energy with the cardiac signal sensed from the patient P.

In some embodiments, the generator180receives feedback from the cardiac monitor110and responds based on the received information. In some embodiments, the generator180receives information regarding the heart rate of the patient and either halts delivery of energy or modifies the energy delivery, such as by selecting a different energy delivery algorithm152. In some embodiments, the generator180halts delivery of energy when the heart rate reaches or drops below a threshold value, such as 30 beats per minute (bpm) or 20 bpm. Optionally, the generator may provide an indicator, such as a visual or auditory indicator, when the heart rate reaches or drops below a lower threshold value, such as providing a flashing yellow light when the heart rate reaches 30 bpm and a solid red light when the heart rate reaches 20 bpm. Such safety measures ensure that the treatment energy is not delivered at an inappropriate time given that low sporadic heart rates may indicate erroneous readings.

In some embodiments, the generator108modifies the energy delivery based on the information from the cardiac monitor110. For example, in some embodiments, energy delivery is provided in a 1:1 ratio when the heart rate is in a predetermined range, such as between 40 bpm and 120 bpm. This involves delivery of PEF energy at the appropriate interval of each heart beat. In some embodiments, the generator108modifies the energy delivery if the heart rate exceeds this range, such as if the heart rate exceeds 120 bpm. In some embodiments, the energy delivery is modified to a 2:1 ratio (two heartbeats:one delivery) wherein PEF energy is delivered at the appropriate interval of every other heart beat. It may be appreciated that various ratios of the form m:n (where m and n are integers) may be utilized, such as 3:1, 3:2, 4:1, 4:3 5:1, etc. 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 that is used for recording during procedures but is also available for pacing. Such pacing may be triggered by the generator108or the cardiac monitor110.

In some embodiments, the generator108halts energy delivery or modifies the 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 generator108modifies energy delivery based on sensed temperature (e.g. on the catheter102, in nearby tissue, in nearby structures, etc.). In some embodiments, energy delivery is modified to a 2:1 ratio, wherein PEF energy is delivered at the appropriate interval of every other heart beat, when the temperature reaches a predetermined threshold value. Such a modification reduces any small thermal effects, thereby reducing sensed temperature. It may be appreciated that various ratios may be utilized, such as 3:1, 3:2, 4:3, 4:1, 5:1, etc.

As mentioned previously, one or more energy delivery algorithms152are programmable, or can be pre-programmed, into the generator108for delivery to the patient P. The one or more energy delivery algorithms152specify electric signals which provide energy delivered to the cardiac tissue which are non-thermal (e.g. below a threshold for thermal ablation; below a threshold for inducing coagulative thermal damage), reducing or avoiding inflammation, and/or preventing denaturation of stromal proteins in the luminal structures. It may be appreciated that the non-thermal energy is also not cryogenic (i.e. it is above a threshold for thermal damage caused by freezing). Thus, the temperature of the target tissue remains in a range between a baseline body temperature (such as 35° C.-37° C. but can be as low as 30° C.) and a threshold for thermal ablation. Thus, targeted ranges of tissue temperature include 30-65° C., 30-60° C., 30-55° C., 30-50° C., 30-45° C., 30-35° C. Thus, lesions in the heart tissue are not created by thermal injury as the temperature of the tissue remains below a threshold for thermal ablation (e.g. 65° C.). In addition, the impedance of the tissue typically remains below a threshold generated by thermal ablation. Charring and thermal injury of tissue changes the conductivity of the heart tissue. This increase in impedance/reduction in conductivity often indicates thermal injury and reduces the ability of the tissue to receive further energy. In some instances, the impedance of the system circuit from the cathode to the anode remains in the range of 25-250Ω, or 50-200Ω during delivery of PEF energy. In general, the algorithms152are tailored to affect tissue to a pre-determined depth and/or volume and/or to target specific types of cellular responses to the energy delivered. However, it may be appreciated that the pulsed electric field energy described herein may be utilized more liberally than other types of energy, such as those that cause thermal injury, without negative effects. For instance, since the energy does not cause thermal injury, tissue can be over-treated to ensure sufficient lesion formation. For example, in a tissue layer that is 2 mm thick, energy sufficient to create a lesion having a depth of 6 mm can be applied to the tissue to ensure a transmural lesion. Typically, the additional energy is dissipated away from nearby critical structures through transverse tissue planes. In particular, the pericardial fluid surrounding the heart serves to dissipate energy, protecting extracardiac structures, such as the esophagus, phrenic nerve, coronary arteries, lungs, and bronchioles, from injury. This is not the case when delivering energy that creates lesions by thermal injury. In those cases, the propagation of conductive thermal energy beyond the targeted myocardial tissue can result in thermal injury to non-targeted extracardiac structures. Excessive thermal injury to the esophagus may result in esophageal ulcers that can degrade to a life-threatening atrio-esophageal fistula. Thermal injury to the phrenic nerve may result in permanent diaphragmatic paralysis leading to permanent shortness of breath and fatigue. Thermal injury to the coronary arteries can result in coronary spasm that can lead to temporary, or even permanent, chest pressure/pain. In addition, thermal lesions in the heart, 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 pathologic process is related to thermal injury to the tissue that induces post-procedure fibrosis and scaring. Stenosis has been described in patients treated with many forms of thermal energy, including radiofrequency energy and cryoablation.

Since the PEF lesions described herein are not created by thermal injury, rates of “false positive” confirmation of electrical conduction blocks are also reduced. Thermal injury may result in acute myocardial edema (i.e. tissue fluid accumulation and swelling). When testing electrical conductivity across an area of thermally ablated tissue, the tissue may appear to block electrical conduction however such blocking may simply be the result of temporary edema. After a period of recovery to allow the swelling to subside, this area of treated tissue will no longer have transmural, non-conduction. In addition, acute edema due to thermal injury also diminishes the ability to re-treat an area of tissue. Once an area of tissue has undergone an amount of thermal injury, the resulting edema changes the resistive and conductive thermal properties of the tissue. Therefore, effects similar to the initial response in the tissue are difficult to obtain. Thus, any attempted re-treatment is less effective both acutely and chronically. These issues are avoided with the delivery of the energy described herein.

FIG.3illustrates a portion of the heart H showing a cut-away of the right atrium RA and left atrium LA in the treatment of atrial fibrillation. The largest pulmonary veins are the four main pulmonary veins (right superior pulmonary vein RSPV, right inferior pulmonary vein RIPV, left superior pulmonary vein LSPV and left inferior pulmonary vein LIPV), two from each lung that drain into the left atrium LA of the heart H. Each pulmonary vein is linked to a network of capillaries in the alveoli of each lung and bring oxygenated blood to the left atrium LA. The left atrial musculature extends from the left atrium LA and envelopes the proximal pulmonary veins. The superior veins, which have longer muscular sleeves, have been reported to be more arrhythmogenic than the inferior veins. In general, the length of the pulmonary vein sleeves varies between 13 mm and 25 mm. Pulmonary vein morphology has been reported to influence arrhythmogenesis. Likewise, cellular electrophysiology and other aspects of the pulmonary veins are associated with arrhythmogenesis and propagation.

A variety of methods are used to determine which tissue is targeted for treatment, such as anatomical indications and cardiac mapping. Typically, a mapping catheter is chosen to desirably fit the pulmonary vein, adapting to the size and anatomical form of the pulmonary vein. The mapping catheter allows recording of the electrograms from the ostium of the pulmonary vein and from deep within the pulmonary vein; these electrograms are displayed and timed for the user. The treatment catheter102is initially placed deep within the pulmonary vein and gradually withdrawn to the ostium, proximal to the mapping catheter. Mapping and treatment then commences.

The current understanding of pulmonary vein electrophysiology is that most of the fibers in the pulmonary vein are circular and do not carry conduction into the vein. The electrical conduction pathways are longitudinal fibers which extend between the left atrium LA and the pulmonary vein. Pulmonary vein isolation is achieved by ablation of these connecting longitudinal fibers. For the left-sided pulmonary veins, pacing of the distal coronary sinus tends to increase the separation of the atrial signal and the pulmonary vein potential making these more electrically visible. The signals from within the pulmonary vein are evaluated. Each individual signal consists of a far field atrial signal, which is generally of low amplitude, and a sharp local pulmonary vein spike. The earliest pulmonary vein spike represents the site of the connection of the pulmonary vein and atrium. If the pulmonary vein spike and the atrial potential are examined, on some of the poles of the mapping catheter, these electrograms are widely separated, at other sites there will be a fusion potential of the atrial and PV signal. The latter indicate the sites of the longitudinal fibers and the potential sites for treatment.

In some embodiments, the tissue surrounding the opening of the left inferior pulmonary vein LIPV is treated in a point by point fashion with the use of the treatment catheter102(with assistance of mapping) to create a circular treatment zone around the left inferior pulmonary vein LIPV, as illustrated inFIG.3. In some instances, specialized navigation software can be used to allow appropriate positioning of the treatment catheter120. The delivery electrode122is positioned near or against the target tissue area, and energy is provided to the delivery electrode122so as to create a treatment area A. Since the energy is delivered to a localized area (focal delivery), the electrical energy is concentrated over a smaller surface area, resulting in stronger effects than delivery through an electrode extending circumferentially around the lumen or ostium. It also forces the electrical energy to be delivered in a staged regional approach, mitigating the potential effect of preferential current pathways through the surrounding tissue. These preferential current pathways are regions with electrical characteristics that induce locally increased electric current flow therethrough rather than through adjacent regions. Such pathways can result in an irregular electric current distribution around the circumference of a targeted lumen, which thus can distort the electric field and cause an irregular increase in treatment effect for some regions and a lower treatment effect in other regions. This may be mitigated or avoided with the use of focal therapy which stabilizes the treatment effect around the circumference of the targeted region. Thus, by providing the energy to certain regions at a time, the electrical energy is “forced” across different regions of the circumference, ensuring an improved degree of treatment circumferential regularity.FIG.4illustrates the repeated application of energy in point by point fashion around the left inferior pulmonary vein LIPV with the use of the treatment catheter102to create a circular treatment zone. As illustrated, in this embodiment each treatment area A overlaps an adjacent treatment area A so as to create a continuous treatment zone. The size and depth of each treatment area A may depend on a variety of factors, such as parameter values, treatment times, tissue characteristics, etc. It may be appreciated that the number of treatment areas A may vary depending on a variety of factors, particularly the unique conditions of each patient's anatomy and electrophysiology. In some embodiments, the number of treatment areas A include one, two, three, four, five, six, seven, eight, nine, ten, fifteen, twenty, twenty five, thirty or more.

When all the electrical connections between the atrium and the vein have been treated, there is electrical silence within the pulmonary vein, with only the far field atrial signal being recorded. Occasionally spikes of electrical activity are seen within the pulmonary vein with no conduction to the rest of the atrium; these clearly demonstrate electrical discontinuity of the vein from the rest of the atrial myocardium.

Additional treatment areas can be created at other locations to treat arrhythmias in either the right or left atrium dependent on the clinical presentation. Testing is then performed to ensure that each targeted pulmonary vein is effectively isolated from the body of the left atrium.

Energy Delivery Algorithms

It may be appreciated that a variety of energy delivery algorithms152may be used. In some embodiments, the algorithm152prescribes a signal having a waveform comprising a series of energy packets wherein each energy packet comprises a series of high voltage pulses. In such embodiments, the algorithm152specifies parameters of the signal such as energy amplitude (e.g., voltage) and duration of applied energy, which is comprised of the number of packets, number of pulses within a packet, and the fundamental frequency of the pulse sequence, to name a few. Additional parameters may include switch time between polarities in biphasic pulses, dead time between biphasic cycles, and rest time between packets, which will be described in more detail in later sections. There may be a fixed rest period between packets, or packets may be gated to the cardiac cycle and are thus variable with the patient's heart rate. There may be a deliberate, varying rest period algorithm or no rest period may also be applied between packets. A feedback loop based on sensor information and an auto-shutoff specification, and/or the like, may be included.

FIG.5illustrates an embodiment of a waveform400of a signal prescribed by an energy delivery algorithm152. Here, two packets are shown, a first packet402and a second packet404, wherein the packets402,404are separated by a rest period406. In this embodiment, each packet402,404is comprised of a first biphasic cycle (comprising a first positive pulse peak408and a first negative pulse peak410) and a second biphasic cycle (comprising a second positive pulse peak408′ and a second negative pulse peak410′). The first and second biphasic pulses are separated by dead time412(i.e. a pause) between each biphasic cycle. In this embodiment, the biphasic pulses are symmetric so that the set voltage416is the same for the positive and negative peaks. Here, the biphasic, symmetric waves are also square waves such that the magnitude and time of the positive voltage wave is approximately equal to the magnitude and time of the negative voltage wave.

The voltages used and considered may be the tops of square-waveforms, may be the peaks in sinusoidal or sawtooth waveforms, or may be the RMS voltage of sinusoidal or sawtooth waveforms. In some embodiments, the energy is delivered in a monopolar fashion and each high voltage pulse or the set voltage416is between about 500V to 10,000V, particularly about 1000V-2000V, 2000V-3000V, 3000V-3500V, 3500V-4000V, 3500V-5000V, 3500V-6000V, including all values and subranges in between including about 1000V, 2000V, 2500V, 2800V, 3000V, 3300V, 3500V, 3700V, 4000V, 4500V, 5000V, 5500V, 6000V to name a few.

It may be appreciated that the set voltage416may vary depending on whether the energy is delivered in a monopolar or bipolar fashion. In bipolar delivery, a lower voltage may be used due to the smaller, more directed electric field. The bipolar voltage selected for use in therapy is dependent on the separation distance of the electrodes, whereas the monopolar electrode configurations that use one or more distant dispersive pad electrodes may be delivered with less consideration for exact placement of the catheter electrode and dispersive electrode placed on the body. In monopolar electrode embodiments, larger voltages are typically used due to the dispersive behavior of the delivered energy through the body to reach the dispersive electrode, on the order of 10 cm to 100 cm effective separation distance. Conversely, in bipolar electrode configurations, the relatively close active regions of the electrodes, on the order of to 10 cm, including 1 mm to 1 cm, results in a greater influence on electrical energy concentration and effective dose delivered to the tissue from the separation distance. For instance, if the targeted voltage-to-distance ratio is 3000 V/cm to evoke the desired clinical effect at the appropriate tissue depth (1.3 mm), if the separation distance is changed from lmm to 1.2 mm, this would result in a necessary increase in treatment voltage from300to about 360 V, a change of 20%.

It may be appreciated that the number of biphasic cycles per second of time is the frequency when a signal is continuous. In some embodiments, biphasic pulses are utilized to reduce undesired muscle stimulation, particularly cardiac muscle stimulation. In other embodiments, the pulse waveform is monophasic and there is no clear inherent frequency. Instead, a fundamental frequency may be considered by doubling the monophasic pulse length to derive the frequency. In some embodiments, the signal has a frequency in the range 50 kHz-1 MHz, more particularly 50 kHz-1000 kHz. It may be appreciated that at some voltages, frequencies at or below 100-250 kHz may cause undesired muscle stimulation. Therefore, in some embodiments, the signal has a frequency in the range of 300-800 kHz, 400-800 kHz or 500-800 kHz, such as 300 kHz, 400 kHz, 450 kHz, 500 kHz, 550 kHz, 600 kHz, 650 kHz, 700 kHz, 750 kHz, 800 kHz. In addition, cardiac synchronization is typically utilized to reduce or avoid undesired cardiac muscle stimulation during sensitive rhythm periods. It may be appreciated that even higher frequencies may be used with components which minimize signal artifacts.

The frequency of the waveform delivered may vary relative to the treatment voltage in synchrony to retain adequate treatment effect. Such synergistic changes would include the decrease in frequency, which evokes a stronger effect, combined with a decrease in voltage, which evokes a weaker effect. For instance, in some cases the treatment may be delivered using 3000 V in a monopolar fashion with a waveform frequency of 600 kHz, while in other cases the treatment may be delivered using 2000 V with a waveform frequency of 400 kHz.

As mentioned, the algorithm152typically prescribes a signal having a waveform comprising a series of energy packets wherein each energy packet comprises a series of high voltage pulses. The cycle count420is half the number of pulses within each biphasic packet. Referring toFIG.5, the first packet402has a cycle count420of two (i.e. four biphasic pulses). In some embodiments, the cycle count420is set between 2 and 1000 per packet, including all values and subranges in between. In some embodiments, the cycle count420is 5-1000 per packet, 2-10 per packet, 2-20 per packet, 2-25 per packet, 10-20 per packet, 20 per packet, 20-30 per packet, 25 per packet, 20-40 per packet, 30 per packet, 20-50 per packet, 30-60 per packet, up to 60 per packet, up to 80 per packet, up to 100 per packet, up to 1,000 per packet or up to 2,000 per packet, including all values and subranges in between.

The packet duration is determined by the cycle count, among other factors. For a matching pulse duration (or sequence of positive and negative pulse durations for biphasic waveforms), the higher the cycle count, the longer the packet duration and the larger the quantity of energy delivered. In some embodiments, packet durations are in the range of approximately 50 to 1000 microseconds, such as 50 μs, 60 μs, 70 μs, 80 μs, 90 μs, 100 μs, 125 μs, 150 μs, 175 μs, 200 μs, 250 μs, 100 to 250 μs, 150 to 250 μs, 200 to 250 μs, 500 to 1000 μs to name a few. In other embodiments, the packet durations are in the range of approximately 100 to 1000 microseconds, such as 150 μs, 200 μs, 250 μs, 500 μs, or 1000 μs.

The number of packets delivered during treatment, or packet count, typically includes 1 to 250 packets including all values and subranges in between. In some embodiments, the number of packets delivered during treatment comprises 10 packets, 15 packets, 20 packets, 25 packets, 30 packets or greater than 30 packets.

E. Rest Period

In some embodiments, the time between packets, referred to as the rest period406, is set between about 0.001 seconds and about 5 seconds, including all values and subranges in between. In other embodiments, the rest period406ranges from about 0.01-0.1 seconds, including all values and subranges in between. In some embodiments, the rest period406is approximately 0.5 ms-500 ms, 1-250 ms, or 10-100 ms to name a few.

In some embodiments, the signal is synced with the cardiac rhythm so that each packet is delivered synchronously within a designated period relative to the heartbeats, thus the rest periods coincide with the heartbeats. It may be appreciated that the packets that are delivered within each designated period relative to the heartbeats may be considered a batch or bundle. Thus, each batch has a desired number of packets so that at the end of a treatment period, the total desired number of packets have been delivered. Each batch may have the same number of packets, however in some embodiments, batches have varying numbers of packets.

In some embodiments, only one packet is delivered between heartbeats. In such instances, the rest period may be considered the same as the period between batches. However, when more than one packet is delivered between batches, the rest time is typically different than the period between batches. In such instances, the rest time is typically much smaller than the period between batches. In some embodiments, each batch includes 1-10 packets, 1-5 packets, 1-4 packets, 1-3 packets, 2-3 packets, 2 packets, 3 packets, 4 packets 5 packets, 5-10 packets, to name a few. In some embodiments, each batch has a period of 0.5 ms-1 sec, 1 ms-1 sec, 10 ms-1 sec, 10 ms-100 ms, to name a few. In some embodiments, the period between batches is variable, depending on the heart rate of the patient. In some instances, the period between batches is 0.25-5 seconds.

Treatment of a tissue area ensues until a desired number of batches are delivered to the tissue area. In some embodiments, 2-50 batches are delivered per treatment, wherein a treatment is considered treatment of a particular tissue area. In other embodiments, treatments 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.

G. Switch Time and Dead Time

A switch time is a delay or period of no energy that is delivered between the positive and negative peaks of a biphasic pulse, as illustrated inFIG.5. In some embodiments, the switch time ranges between about 0 to about 1 microsecond, including all values and subranges in between. In other embodiments, the switch time ranges between 1 and 20 microseconds, including all values and subranges in between. In other embodiments, the switch time ranges between about 2 to about 8 microsecond, including all values and subranges in between.

Delays may also be interjected between each biphasic cycle, referred as “dead-time”. Dead time occurs within a packet, but between biphasic pulses. This is in contrast to rest periods which occur between packets. In other embodiments, the dead time412is in a range of approximately 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 in between. In some embodiments, the dead time412is in the range of 0.2 to 0.3 microseconds. Dead time may also be used to define a period between separate, monophasic, pulses within a packet.

Delays, such as switch times and dead times, are introduced to a packet to reduce the effects of biphasic cancellation within the waveform. In some instances, the switch time and dead time are both increased together to strengthen the effect. In other instances, only switch time or only dead time are increased to induce this effect.

FIG.5illustrated an embodiment of a waveform400having symmetric pulses such that the voltage and duration of pulse in one direction (i.e., positive or negative) is equal to the voltage and duration of pulse in the other direction.FIG.6illustrates an example waveform400prescribed by another energy delivery algorithm152wherein the waveform400has voltage imbalance. Here, two packets are shown, a first packet402and a second packet404, wherein the packets402,404are separated by a rest period406. In this embodiment, each packet402,404is comprised of a first biphasic cycle (comprising a first positive pulse peak408having a first voltage V1and a first negative pulse peak410having a second voltage V2) and a second biphasic cycle (comprising a second positive pulse peak408′ having first voltage V1and a second negative pulse peak410′ having a second voltage V2). Here the first voltage V1is greater than the second voltage V2. The first and second biphasic cycles are separated by dead time412between each pulse. Thus, the voltage in one direction (i.e., positive or negative) is greater than the voltage in the other direction so that the area under the positive portion of the curve does not equal the area under the negative portion of the curve. This unbalanced waveform may result in a more pronounced treatment effect as the dominant positive or negative amplitude leads to a longer duration of same charge cell membrane charge potential. In this embodiment, the first positive peak408has a set voltage416(V1) that is larger than the set voltage416′ (V2) of the first negative peak410.FIG.7illustrates further examples of waveforms having unequal voltages. Here, four different types of packets are shown in a single diagram for condensed illustration. The first packet402is comprised of pulses having unequal voltages but equal pulse widths, along with no switch times and dead times. Thus, the first packet402is comprised of four biphasic pulses, each comprising a positive peak408having a first voltage V1and a negative peak410having a second voltage V2). Here the first voltage V1is greater than the second voltage V2. The second packet404is comprised of pulses having unequal voltages but symmetric pulse widths (as in the first pulse402), with switch times equal to dead times. The third packet405is comprised of pulses having unequal voltages but symmetric pulse widths (as in the first pulse402), with switch times that are shorter than dead times. The fourth packet407is comprised of pulses having unequal voltages but symmetric pulse widths (as in the first pulse402), with switch times that are greater than dead times. It may be appreciated that in some embodiments, the positive and negative phases of biphasic waveform are not identical, but are balanced, where the voltage in one direction (i.e., positive or negative), is greater than the voltage in the other direction but the length of the pulse is calculated such that the area under the curve of the positive phase equals the area under the curve of the negative phase.

In some embodiments, imbalance includes pulses having pulse widths of unequal duration. In some embodiments, the biphasic waveform is unbalanced, 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 greater than the duration of the other direction, so that the area under the curve of the positive portion of the waveform does not equal the area under the negative portion of the waveform.

FIG.8illustrates further examples of waveforms having unequal pulse widths. Here, four different types of packets are shown in a single diagram for condensed illustration. The first packet402is comprised of pulses having equal voltages but unequal pulse widths, along with no switch times and dead times. Thus, the first packet402is comprised of four biphasic pulses, each comprising a positive peak408having a first pulse width PW1and a negative peak410having a second pulse width PW2). Here the first pulse width PW1is greater than the second pulse width PW2. The second packet404is comprised of pulses having equal voltages but unequal pulse widths (as in the first pulse402), with switch times equal to dead times. The third packet405is comprised of pulses having equal voltages but unequal pulse widths (as in the first pulse402), with switch times that are shorter than dead times. The fourth packet407is comprised of pulses having equal voltages but unequal pulse widths (as in the first pulse402), with switch times that are greater than dead times.

FIG.9illustrates an example waveform400prescribed by another energy delivery algorithm152wherein the waveform is monophasic, a special case of imbalance whereby there is only a positive or only a negative portion of the waveform. Here, two packets are shown, a first packet402and a second packet404, wherein the packets402,404are separated by a rest period406. In this embodiment, each packet402,404is comprised of a first monophasic pulse430and a second monophasic pulse432. The first and second monophasic pulses430,432are separated by dead time412between each pulse. This monophasic waveform could lead to a more desirable treatment effect as the same charge cell membrane potential is maintain for longer durations. However, adjacent muscle groups will be more stimulated by the monophasic waveform, compared to a biphasic waveform.

FIG.10illustrates further examples of waveforms having monophasic pulses. Here, four different types of packets are shown in a single diagram for condensed illustration. The first packet402is comprised of pulses having identical voltages and pulse widths, with no switch times (because the pulses are monophasic) and a dead time equal to the active time. In some cases, there may be less dead time duration than the active time of a given pulse. Thus, the first packet402is comprised of three monophasic pulses430, each comprising a positive peak. In instances where the dead time is equal to the active time, the waveform may be considered unbalanced with a fundamental frequency representing a cycle period of 2× the active time and no dead time. The second packet404is comprised of monophasic pulses430having equal voltages and pulse widths (as in the first packet402), with larger dead times. The third packet405is comprised of monophasic pulses430having equal voltages and pulse widths (as in the first packet402), and even larger dead times. The fourth packet407is comprised of monophasic pulses430having equal voltages and pulse widths (as in the first packet402), with yet larger dead times.

In some embodiments, an unbalanced waveform is achieved by delivering more than one pulse in one polarity before reversing to an unequal number of pulses in the opposite polarity.FIG.11illustrates further examples of waveforms having such phase imbalances. Here, four different types of packets are shown in a single diagram for condensed illustration. The first packet402is comprised of four cycles having equal voltages and pulse widths, however, opposite polarity pulses are intermixed with monophasic pulses. Thus, the first cycle comprises a positive peak408and a negative peak410. The second cycle is monophasic, comprising a single positive pulse with no subsequent negative pulse430. This then repeats. The second packet404is comprised of intermixed biphasic and monophasic cycles (as in the first packet402), however the pulses have unequal voltages. The third packet405is comprised of intermixed biphasic and monophasic cycles (as in the first packet402), however the pulses have unequal pulse widths. The fourth packet407is comprised of intermixed biphasic and monophasic pulses (as in the first packet402), however the pulses have unequal voltages and unequal pulse widths. Thus, multiple combinations and permutations are possible.

FIG.12illustrates an example waveform400prescribed by another energy delivery algorithm152wherein the pulses are sinusoidal in shape rather than square. Again, two packets are shown, a first packet402and a second packet404, wherein the packets402,404are separated by a rest period406. In this embodiment, each packet402,404is comprised three biphasic pulses440,442,444. And, rather than square waves, these pulses440,442,444are sinusoidal in shape. One benefit of a sinusoidal shape is that it is balanced or symmetrical, whereby each phase is equal in shape. Balancing may assist in reducing undesired muscle stimulation. It may be appreciated that in other embodiments the pulses have decay-shaped waveforms.

Energy delivery may be actuated by a variety of mechanisms, such as with the use of a button164on the catheter102or a foot switch168operatively connected to the generator104. Such actuation 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 the tissue maintains the temperature at or in the tissue below a threshold for thermal ablation. In addition, the doses may be titrated or moderated over time so as to further reduce or eliminate thermal build up during the treatment procedure. Instead of inducing thermal damage, defined as protein coagulation at sites of danger to therapy, the energy dose provide energy at a level which induces treats the condition without damaging sensitive tissues.

Treatment Catheter Designs

The systems and devices described herein may be used with a variety of types and styles of treatment catheters102. In some embodiments, the treatment catheters102are designed to deliver focal therapy and in other embodiments, the treatment catheters102are designed to deliver “one shot” therapy. Focal therapy is considered to be a therapy wherein the energy is delivered in a sequence, such as the repeated application of energy in point by point fashion, such as around a pulmonary vein to create a circular treatment zone, such as previously illustrated inFIG.4, or along a line, curve, etc. One shot therapy is considered to be a therapy wherein the energy is delivered via an energy delivery body or delivery electrode(s) to the entire circumference of the entrance to the pulmonary vein in “one shot”, however such delivery may be repeated if desired. This may optionally include rotation of the energy delivery body or electrode122between “shots” if desired.

Focal Therapy

As mentioned previously, focal therapy is often performed with the use of a delivery electrode122having a cylindrical shape with a distal face, such as illustrated inFIGS.2A-2B. Here the distal face is flat and circular. In some embodiments, the distal face of the delivery electrode122has a diameter of 2-3 mm. In such embodiments, when the treatment catheter102is positioned perpendicularly to the tissue, the distal face is able to cover a portion of tissue having a diameter of 2-3 mm. However, a larger portion of tissue may be covered with alternative device designs described herein. Such larger coverage may provide larger lesion sizes with a single application.

FIGS.13A-13Cillustrate an embodiment of a treatment catheter502configured for focal delivery that optionally covers a larger area of tissue than a cylindrically shaped delivery electrode typically found on conventional RF catheters. Here, the catheter502comprises an elongate shaft520having at an energy delivery body near its distal end524, wherein the energy delivery body comprises at least one delivery electrode522. In particular, in this embodiment, the catheter502includes a plurality of electrodes that are arranged to form a continuous shape (i.e. a continuous outer rim) and therefore, optionally, a continuous lesion. A continuous lesion can be formed by energizing the plurality of the electrodes, either simultaneously or non-simultaneously, however it may be appreciated that in some embodiments a subset (including just one) of the plurality of electrodes may be energized if desired so as to create a lesion that is less than the continuous shape. It may also be appreciated that in such instances a continuous lesion may be ultimately created by manipulation of the catheter502, such as by rotation or repositioning, if it is not desired to create a continuous lesion in the initial position.

FIG.13Aprovides a side view of the catheter502, wherein the at least one delivery electrode522comprises four loop-shaped electrodes: a first electrode530, a second electrode532, a third electrode534and a fourth electrode536. Each of the plurality of electrodes530,532,534,536is comprised of a wire508that is formed or shaped into a petal or loop shape having a narrower shape near the shaft520and a larger, wider shape extending away from the shaft520. Thus, the electrodes530,532,534,536fan out or extend outwardly from the shaft520in a flower bloom shape, as shown in the perspective view ofFIG.13B. In this embodiment, the sides540of each of the loop shapes are disposed adjacent to each other and are joined together. Thus, the first electrode530is joined on one side to the adjacent second electrode532and on the opposite side to the adjacent fourth electrode536. This provides stability to the overall design, maintaining the relative position of the electrodes530,532,534,536throughout delivery and use. In some embodiments, the sides540are joined with a material that insulates the sides540so as to prevent conduction of energy therethrough. This concentrates energy delivery through the distal edges542of each of the loop shapes which is configured to contact the tissue.

FIG.13Cprovides a top-down view of the electrodes530,532,534,536pressed against a surface. As shown, the distal edges542of each loop shape contact the surface and together form a ring or circular shape, wherein the side540appear as “spokes” to the “wheel”. When the distal edges542are pressed against tissue and energy is delivered therethrough. Typically, the resulting lesion is larger than the width of the wire508. Therefore, any small gaps between the loop shapes will not diminish the lesion since the resulting lesion overwhelms any effect of small gaps. In some embodiments, the wire508has a diameter of 0.0075 inches and the resulting lesion has a width of 12 mm (i.e. measured across the width of the wire). Thus, in some embodiments, the lesion has a ring shape, circular shape or donut shape. It may be appreciated that in some embodiments, the lesion is large enough to connect through the center of the ring shape so that the lesion appears to be a solid circle. In some embodiments, the catheter502includes an additional central electrode548, such as illustrated inFIGS.13A-13C. The central electrode548extends distally from the central or longitudinal axis of the shaft520. In some embodiments, the central electrode548does not extend longitudinally to the plane of the distal edges542when in the relaxed position, as illustrated inFIGS.13A-13B. In such embodiments, the central electrode548contacts the surface of the tissue when the distal edges542are pressed against the surface of the tissue, splaying the loops apart so that they flatten against the tissue as inFIG.13C. Delivery of energy through the central electrode548in this position creates a central lesion which assists in creating a continuous lesion within the footprint of the loop shaped electrodes530,532,534,536.

FIGS.14A-14Dillustrate delivery of the embodiment of the catheter502ofFIGS.13A-13C. It may be appreciated that the wire508may be comprised of a variety of materials, such as nitinol or drawn filled tube (e.g. 10% platinum/nitinol), to name a few. In this embodiment, the wire508is flexible so as to collapse within a delivery sheath550, as illustrated inFIG.14A. This allows the distal end of the catheter502to be successfully advanced to the target tissue site. Typically, the delivery sheath550has an inner diameter in the range of 2.5 mm to 3.5 mm. Incremental exposure of the electrodes530,532,534,536can be achieved by advancement of the catheter502within the delivery sheath550or the delivery sheath550may be retracted to reveal the distal end of the catheter502.FIG.14Billustrates the distal end of the catheter502emerging from the delivery sheath550, wherein the loop shaped electrodes530,532,534,536begin splaying outwardly.FIG.14Cillustrates the catheter502further emerged from the delivery sheath550, wherein the loop shaped electrodes530,532,534,536expand further radially outward from the longitudinal axis552of both the catheter502and the delivery sheath550.FIG.14Dillustrates full exposure of the loop shaped electrodes530,532,534,536wherein the loop shaped electrodes530,532,534,536are able to recoil to their fullest relaxed expansion. It may be appreciated that pressing the loop shaped electrodes530,532,534,536against a surface may further expand the loop shaped electrodes530,532,534,536to create an even larger footprint. In some embodiments, the largest diameter is 9-15 mm which may create a lesion with a similar or larger diameter due to electric field effects.

In some embodiments, the overall lesion size created by the footprint of the treatment catheter502ofFIGS.13A-13Cis larger than the lesion size created by the footprint of the solid tipped treatment catheter102ofFIGS.2A-2B.FIG.15provides a visual illustration of the respective end effectors adjacent to each other in contact with tissue. Here, the solid tipped treatment catheter102has a delivery electrode122having a circular face of 3 mm in diameter. The treatment catheter502has a delivery electrode522comprises four loop-shaped electrodes wherein together the electrodes530,532,534,536form a circular face of 9-10 mm in diameter. This larger footprint is at least three times the size of the smaller footprint. In some instances, the larger footprint is up to six times the size of the smaller footprint. Thus, the difference in size between the delivery electrodes and therefore footprints is typically in the range of 3-6 times. Since the delivery electrode122of the solid tipped treatment catheter102typically has the same diameter as its shaft, the size of the delivery electrode522in its expanded configuration has the same relationship to the shaft of the treatment catheter502as it does to the solid tipped treatment catheter102(i.e. the delivery electrode in its expanded configuration is 3-6 times the diameter of the shaft of the treatment catheter502). This larger diameter footprint can provide a number of advantages. In some instances, the larger footprint allows the user to perform a complete treatment protocol with less lesions. For example, when circling a pulmonary vein with the use of a solid tipped treatment catheter102, as illustrated inFIG.4, the user may create 35 lesions to complete the full circle lesion. However, when performing this same procedure with the treatment catheter502ofFIGS.13A-13C, the user may create the full circle lesion with 12 lesions. It may be appreciated that the treatment catheter502may be configured to have footprints of a variety of different diameters, and such diameters will proportionally correspond to the number of lesions desired to create a complete circle. Such logic follows other shaped lesions, such as line lesions and other types of treatments. Often times, the larger the lesion, the lesser the number of lesions is utilized to perform a treatment. This typically reduces the treatment time and leads to shorter procedures. Another advantage of the loop-shaped electrode design is the ability to create a larger footprint while maintaining healthy tissue within the center of the footprint. Thus, when ring shaped lesions are created surrounding healthy tissue, more of the healthy cardiac tissue is maintained than if the lesion were a solid disk shape. Adjacent ring-shaped lesions are able to block conduction through the cardiac tissue as effectively as solid disk-shaped lesions while maintaining a higher percentage of healthy tissue. In some embodiments, the ring shape maintains 25% more healthy tissue.

It may be appreciated that, in some embodiments, the overall diameter or footprint size may be controlled by adjusting the deployment of the loop shaped electrodes530,532,534,536from the delivery sheath550. For example, a smaller diameter may be achieved by only advancing the loop shaped electrodes530,532,534,536partially from the sheath550, such as inFIGS.14B-14C. Likewise, a larger diameter may be achieved by full advancement of the loop shaped electrodes530,532,534,536from the sheath550. In addition, a variety of catheters502may be designed having energy delivery electrodes522of differing maximum diameter to suit a variety of needs.

It may also be appreciated that the overall diameter or footprint size may be configured so that the delivery electrode522is able to provide one-shot therapy. Again, one shot therapy is considered to be a therapy wherein the energy is delivered via the delivery electrode522to the entire treatment area, such as the circumference of the entrance to the pulmonary vein, in “one shot”, however such delivery may be repeated if desired. This may optionally include rotation of the electrode122between “shots” if desired. In such embodiments, the overall diameter may be in the range of 22 to 33 mm.

It may be appreciated that the energy delivery body or energy delivery electrode522of the treatment catheter502may have any suitable number of loop-shaped electrodes, including two, three, four, five, six, seven, eight, nine, ten or more. Likewise, the electrodes may be energizable together or independently. When the electrodes are energized independently, the electrodes may be energized sequentially or in various patterns. Likewise, in some embodiments a subset (including just one) of the plurality of electrodes may be energized. This provides a wide variety of options to create desired lesions.

FIG.16illustrates another embodiment of a treatment catheter602configured for focal delivery, that optionally covers a larger area of tissue than a cylindrically shaped delivery electrode typically found on conventional RF catheters, or for one shot therapy. This embodiment is similar to the embodiment ofFIGS.13A-13Cin that the catheter602includes a plurality of loop-shaped electrodes that are arranged to form a continuous shape (i.e. a continuous outer rim) and therefore, optionally, a continuous lesion. In this embodiment, the delivery electrode622comprises six loop-shaped electrodes (rather than four): a first electrode630, a second electrode632, a third electrode634, a fourth electrode636, a fifth electrode638and a sixth electrode640. However, it may be appreciated that any number of electrodes may be utilized, such as up to 10-12 electrodes. Again, a continuous lesion can be formed by energizing the plurality of the electrodes, either simultaneously or non-simultaneously, however it may be appreciated that in some embodiments a subset (including just one) of the plurality of electrodes may be energized if desired so as to create a lesion that is less than the continuous shape. It may also be appreciated that in such instances a continuous lesion may be ultimately created by manipulation of the catheter602, such as by rotation or repositioning, if it is not desired to create a continuous lesion in the initial position.

As shown inFIG.16, each of the plurality of electrodes630,632,634,636,638,640fan out or extend outwardly from the shaft620in a flower bloom shape upon actuation. In this embodiment, the sides642of each of the loop shapes are disposed adjacent to each other and are joined together. Thus, the first electrode630is joined on one side to the adjacent second electrode632and on the opposite side to the adjacent sixth electrode640.

It may be appreciated that the overall diameter of the energy delivery body or delivery electrode622may be configured for focal therapy, for one shot therapy or for both.FIG.16illustrates an embodiment sized for one shot therapy wherein the overall diameter or footprint size is 30 mm, as indicated by the ruler measurement. It may be appreciated that such diameters are typically in the range of 22 to 33 mm for one shot therapy. Likewise,FIG.17illustrates the embodiment ofFIG.16positioned against a laboratory benchtop model of the entrance to the pulmonary vein PV. As shown, together the outer rims of the electrodes630,632,634,636,638,640extend around the circumference of the model entrance to the pulmonary vein so as to provide one shot therapy. It may be appreciated that the dimensions may be adjusted for focal delivery, either by progressive deployment (similar toFIGS.14A-14D) or by generation of a delivery electrode622having a smaller overall diameter, such as is in the range of 9-15 mm. Combination use for focal and one shot therapy will be described herein.

FIGS.18A-18Billustrate the delivery electrode622deployed from a delivery sheath650so that the electrodes630,632,634,636,638,640extend substantially perpendicular to a longitudinal axis of the delivery sheath650. In this configuration, the external rims of the electrodes630,632,634,636,638,640have expanded to reach their maximum diameter or footprint size.FIG.18Billustrates the delivery electrode622positioned against a flat surface, such as representing a tissue plane, which illustrates that the electrodes630,632,634,636,638,640are able to lay substantially flat against the surface.

Further extension of the electrodes630,632,634,636,638,640from the sheath650allows the petal shaped electrodes630,632,634,636,638,640to curve downward so that the external rims of the electrodes630,632,634,636,638,640are disposed proximally of the distal tip of the sheath650, as illustrated inFIG.19. This is achieved by pre-formed curvatures of the sides640which are allowed to recoil toward their pre-formed shape upon further release. The pre-curvature causes the sides640to arc distally and then bend proximally so that the overall shape of the delivery electrode622resembles an umbrella or a mushroom cap. In this configuration, the delivery electrode622is preferentially arranged to deliver energy to surfaces within a lumen, such as within a pulmonary vein PV. Here, positioning of the delivery electrode622against an entrance of a pulmonary vein PV allows the external rim of the electrodes630,632,634,636,638,640to reside along the circumference of the pulmonary vein PV while the sides642extend into the pulmonary vein PV, along the inner lumen of the pulmonary vein PV. In some embodiments, the sides642are insulated so that such positioning provides stability while energy is delivered via the outer rim of the electrodes630,632,634,636,638,640. In other embodiments, the sides642are not insulated so that such positioning allows delivery of energy to portions of the inner lumen of the pulmonary vein PV via the sides642. This may assist in creating larger or more complex lesions.

Further deployment of the electrodes630,632,634,636,638,640exaggerates this shape wherein the sides640are allowed to bend or arc even further, as illustrated inFIG.20. In this configuration, the delivery electrode622is preferentially arranged to deliver focal energy to a surface of tissue by positioning the sides642against the surface. In such an arrangement, the delivery electrode622may be used so that the outer rims of the electrodes630,632,634,636,638,640are not in contact with the tissue and the energy is delivered to the tissue via the sides642. Due to the rounded curvature of the sides642. the delivery electrode622is able to be “rolled” along the tissue, such as having a ball shape wherein the curved surfaces are able to engage the tissue by tilting the shaft620(within the sheath650) of the catheter602. This provides unlimited engagement positions and high flexibility in energy delivery. Thus, this embodiment can transition between configurations to provide either one shot therapy or focal therapy; therefore it is particularly suited for combination use.

It may be appreciated that the embodiment ofFIGS.16-20can optionally deliver via the external rims of the electrodes630,632,634,636,638,640, through the sides642of the pedal shapes or through both, either simultaneously, alternatively or in any combination. Thus, a ring or donut shaped lesion can be created or a solid circular shape lesion can be created, each of various sizes.

FIG.21illustrates an embodiment of a treatment catheter702configured for focal delivery rather than one shot delivery or combination delivery. Here, the lesions formed have a solid circular shape and are therefore primarily suitable for treating tissue surfaces, such as in a point-by-point fashion. This is due to the shape and configuration of its delivery electrode722.FIG.22illustrates an embodiment of the treatment catheter702wherein the energy delivery body or delivery electrode722comprises a plurality of trowel shaped electrodes730,732,734,736extending from a shaft720. Each trowel shaped electrode has a substantially triangular shape wherein a tip738of the triangular shape resides near the center of the formed lesion, the sides740of the triangular shape extend radially outwardly from the center of the formed lesion and the base742of the triangular shape extends along the periphery of the formed lesion. In this embodiment, the tip738is a free end and the base742is attached to the catheter702by a support744. Thus, the tips738of the trowel shaped electrodes730,732,734,736are able to flex distally and proximally to accommodate structural variations in the surface of the tissue against which the delivery electrode722is placed. The tips738and sides740of the trowel shaped electrodes730,732,734,736also help generate a continuous lesion, rather than a donut shaped lesion.

FIG.23illustrates a side view of an embodiment of a treatment catheter702similar to that ofFIGS.21-22. Here, only two trowel shaped electrodes730,732are visible. As shown, the trowel shaped electrodes730,732align along a plane perpendicular the shaft720. The plane is spaced distally from the distal end of the shaft720determined by the length of the supports744. In some embodiments, irrigation is provided by an irrigation lumen760such as extending from the distal end of the shaft720. This allows delivery of irrigation fluid in the area of lesion formation.

It may be appreciated that any suitable number of trowel shaped electrodes may be present, typically three, four, five, six, seven, eight or more. It may also be appreciated that the trowel shaped electrodes may be independently activated, activated together or activated in any combination, such as in pairs, groups or in a sequential pattern of individual or grouped electrodes.

It may also be appreciated that any portion of the trowel shaped electrodes may be insulated to focus energy delivery through a particular area. In this embodiment, the supports744are insulated so as to direct energy through the triangular shaped portions of the trowel shaped electrodes. It may also be appreciated that various sensors, such as microsensors for contact feedback or electroanatomic mapping systems, may be positioned along the trowel shaped electrodes. In this embodiment, such sensors are disposed along the bases744, however sensors may be positioned along any suitable portion.

FIG.24illustrates another embodiment of a treatment catheter802. Here the delivery electrode822comprises a plurality of trowel shaped electrodes830,832,834,836extending from a shaft820. Again, each trowel shaped electrode has a substantially triangular shape wherein a tip838of the triangular shape resides near the center of the formed lesion, the sides840of the triangular shape extend radially outwardly from the center of the formed lesion and the base842of the triangular shape extends along the periphery of the formed lesion. However, in this embodiment, the base842is a free end and the tip838is attached to the catheter802by a support844. In some embodiments, the supports844are pre-curved so as to bias the radially outwardly from the shaft820. Typically, the supports844are comprised of material that provide flexibility and springiness so as to allow the supports844to bend toward the shaft820and then recoil upon release to the pre-curved configuration. This provides the ability to move the trowel shaped electrodes830,832,834,836, such as to create different sized lesions. In this embodiment, the supports844extend along at least a portion of the shaft820, such as within longitudinal grooves852along the shaft820. Likewise, in this embodiment a sheath850is advanceable over the shaft820and the grooves852, holding the supports844within the grooves852. Upon retraction of the sheath850, the supports844are able to recoil toward their pre-curved configuration, moving the trowel shaped electrodes830,832,834,836radially outwardly as shown. It may be appreciated that the amount of movement may be determined by the amount of retraction of the sheath850. Maximum retraction allows maximum expansion of the trowel shaped electrodes830,832,834,836so as to create a maximum sized lesion. Smaller lesions may be created by incrementally advancing the sheath850so as to desirably position the trowel shaped electrodes830,832,834,836.

It may be appreciated that any suitable number of trowel shaped electrodes may be present, typically three, four, five, six, seven, eight or more. It may also be appreciated that the trowel shaped electrodes may be independently activated, activated together or activated in any combination, such as in pairs, groups or in a sequential pattern of individual or grouped electrodes.

It may also be appreciated that any portion of the trowel shaped electrodes may be insulated to focus energy delivery through a particular area. In this embodiment, the supports844are insulated so as to direct energy through the triangular shaped portions of the trowel shaped electrodes. It may also be appreciated that various sensors, such as microsensors for contact feedback or electroanatomic mapping systems, may be positioned along the trowel shaped electrodes. In this embodiment, such sensors are disposed along the bases844, however sensors may be positioned along any suitable portion.

FIG.25illustrates another embodiment of a treatment catheter902. Here the delivery electrode922comprises a single petal, paddle or loop shaped electrode930having a narrower shape near the shaft920and a larger, wider shape extending away from the shaft920. In this embodiment, the electrode930resides in a plane aligned with a longitudinal axis910of the shaft920. However, in this embodiment, the electrode930is comprised of a flexible material which allows the electrode930to bend into a variety of planes relative to the longitudinal axis910including perpendicular to the longitudinal axis910. Bending of the electrode930allows the electrode930to be positioned against a variety of tissue surfaces from a variety of different approaches. For example, the electrode930is not limited to approaching a target tissue from a substantially perpendicular approach but can approach a target tissue from a parallel approach. Thus, the catheter902may be advanced along tissue in a plane parallel to the tissue until the electrode930is positioned adjacent the target tissue. The shaft920may then be angled away from the tissue so that the electrode930engages the tissue. The shaft920may then be further angled away from the tissue to increase engagement and/or contact force of the electrode930with the target tissue. This may be particularly useful when approaching tissue within a lumen, such as a pulmonary vein.

In this embodiment, the catheter902further comprises a sensing loop950that is similar in shape to the single petal, paddle or loop shaped electrode930but is smaller so as to reside inside the loop shape of the electrode930, as illustrated inFIG.25. In this embodiment, the sensing loop950has similar flexibility to the electrode930so it can act in symmetry with the electrode930. Thus, in this embodiment the sensing loop950and the electrode930are connected by a joiner952to ensure that they remain substantially in the same plane. The sensing loop950is comprised of one or more sensors954, such as microsensors for contact feedback or electroanatomic mapping systems.

FIGS.26A-26Billustrate another embodiment of a treatment catheter1002having a paddle shaped delivery electrode1022. Here the delivery electrode1022comprises a single hammerhead paddle shaped electrode1030having a narrower shape near the shaft1020and a wider, hammerhead shape distal from the shaft1020. In addition, the electrode1030includes a plurality of crossbeams1024internal to the overall hammerhead shape which provide support for the hammerhead paddle shape and provide additional areas through which to deliver energy so as to create a more solid lesion. Again, in this embodiment, the electrode1030resides in a plane aligned with a longitudinal axis1010of the shaft1020, and the electrode1030is comprised of a flexible material which allows the electrode1030to bend into a variety of planes relative to the longitudinal axis1010including perpendicular to the longitudinal axis1010. In this embodiment, such bending is achieved with the use of a pullwire1050extending at least partially through the shaft1020and connected with a portion of the electrode1030. Pulling the pullwire1050, as illustrated inFIG.26B, bends the electrode1030into a plane that is at an angle to the longitudinal axis1010. Thus, the electrode1030is able to be desirably arranged prior to contact with the target tissue. This separates positioning from contact force applied during delivery of energy.

FIGS.27-30illustrates another embodiment of a treatment catheter1112. This embodiment is primarily configured for focal delivery of energy to tissue surfaces, such as in a point-by-point fashion. This is due to the shape and configuration of its delivery electrode1122.FIG.27illustrates an embodiment of the treatment catheter1112wherein the delivery electrode1122comprises two semi-circular loop electrodes1130,1132which together form a circular or oval shape which is perpendicular to the shaft1120. The electrodes1130,1132are connected to the shaft1120by supports1144which are typically insulated so as to direct the energy to the semi-circular electrodes1130,1132. In this embodiment, the delivery electrode1122further includes an additional set of two semi-circular inner loops1134,1136which together form a circular or oval shape having a small diameter than the two semi-circular loop electrodes1130,1132. Thus, the two semi-circular inner loops1134,1136reside “inside” the two semi-circular loop electrodes1130,1132, both of which reside on planes which are substantially perpendicular the shaft1120. In this embodiment, the two semi-circular loop electrodes1130,1132and the two semi-circular inner loops1134,1136have an overall cupped or concave shape.FIG.28provides a side view of the embodiment ofFIG.27which illustrates the cupped shape. Likewise,FIG.29provides another side view which illustrates the position of the inner loops1134,1136and loop electrodes1130,1132relative to each other. Thus, the inner loops1134,1136and loop electrodes1130,1132arc in the distal direction so that advancement of the catheter1112toward a target tissue location allows the loop electrodes1130,1132to contact the tissue first followed by the inner loops1134,1136. This ensures contact of the loop electrodes1130,1132with the tissue. In addition, in some embodiments the inner loops1134,1136provide additional stability. For example, in some embodiments the loop electrodes1130,1132are comprised of a flexible material that allows the loop electrodes1130,1132to bend proximally, so as to form a less concave shape (e.g. a more shallow cupped shape, a more flattened shape or a more convex shape) and conform to the target tissue area. In some embodiments, the inner loops1134,1136are comprised of a stiffer material than the loop electrodes1130,1132so as to act as an anchor during placement, providing more confidence to the user. In addition, the stiffer material resists bending more than the loop electrodes1130,1132which limits the bending of the inner loop electrodes1130,1132. In some instances, this is beneficial in avoiding perforation of tissue.

FIG.30illustrates an end view of the delivery electrode1122of the embodiment ofFIGS.27-29. As shown, the loop electrodes1130,1132are insulated along the supports1144and exposed along the outer rim of the overall circular shape. In this embodiment, the inner loops1134,1136include a plurality of microsensors1160spaced along the rims of the overall circular shape. In some embodiments, the microsensors1160are configured for contact feedback, visualization under fluoroscopy or sensing for electroanatomic mapping systems. In other embodiments, the microsensors1160function as electrodes so as to deliver energy in the formation of a lesion. It may be appreciated that in some embodiments, the functionality of the microsensors1160switch back and forth between various options, such as delivering energy during delivery of energy through the loop electrodes1130,1132and sensing between periods of energy delivery. It may also be appreciated that in some embodiments the inner loops1134,1136are comprised of continuous conductive wires so as to provide energy delivery in a manner similar to the loop electrodes1130,1132.

It may be appreciated that any suitable number of loop electrodes1130,1132may be present, typically one, two, three, four, five, six, seven, eight or more. It may also be appreciated that the loop electrodes1130,1132may be independently activated, activated together or activated in any combination, such as in pairs, groups or in a sequential pattern of individual or grouped electrodes. Likewise, any suitable number of inner loops1134,1136may be present, typically one, two, three, four, five, six, seven, eight or more. Further, any suitable number of microsensors1160may be present, such as one, two, three, four, five, six, seven, eight, nine, ten or more. It may be appreciated that the inner loops1134,1136and/or microsensors1160may be independently activated, activated together or activated in any combination, such as in pairs, groups or in a sequential pattern of individual or groups. In some instances, energy delivery via the inner loops1134,1136assists in generating solid lesions rather than donut shaped lesions. Further, it may be appreciated that loop electrodes1130,1132and inner loops1134,1136may be independently activated, activated together or activated in any combination, such as in pairs, groups or in a sequential pattern of individual or grouped electrodes. It may also be appreciated that the loop electrodes1130,1132may include microelectrodes through which energy is delivered rather than via a conductive wire.

As mentioned, the delivery electrode1122is typically sized in configured to deliver focal energy. In such embodiments, the loop electrodes1130,1132form a circular shape having a diameter in the range of 8 to 14 mm. In other embodiments, the delivery electrode1122is configured to provide one-shot delivery. In such embodiments, the loop electrodes1130,1132form a circular shape having a diameter in the range of 22 to 33 mm.

FIGS.31A-31Dillustrate an embodiment of a treatment catheter1202configured for one shot delivery rather than focal delivery. Here, the treatment catheter1202includes a shaft1220that extends into a lumen, such as a pulmonary vein, during placement of the delivery electrode1222. Given this arrangement, the delivery electrode1222is configured to provide energy circumferentially around the lumen, either interiorly, exteriorly or both, with “one-shot” of energy delivery. It may be appreciated that this may be repeated as desired.

In this embodiment, the energy delivery body or delivery electrode1222comprises a mesh basket that is configured to move at least between a collapsed configuration, an expanded configuration and a partially inverted configuration.FIG.31Aillustrates the delivery electrode1222collapsed around the shaft1220upon which it is mounted so that it is able to be housed within a sheath1250.FIG.31Billustrates the delivery electrode1222in an expanded configuration. This may be achieved by retracting the sheath1250or advancing the shaft1220. In some embodiments, the delivery electrode1222is self-expanding upon release from the sheath1250. In other embodiments, the mesh basket is coupled with an additional shaft that is movable in relation to the shaft1220wherein advancement of the additional shaft expands the mesh basket.

In some embodiments, the mesh basket is comprised of a plurality of wires that are energizable in unison, such as to provide energy delivery in a monopolar fashion. It may be appreciated that portions of the mesh basket may be insulated so as to focus energy delivery through particular uninsulated portions of the mesh basket. This may also assist in reducing loss of energy to the surrounding blood environment. In other embodiments, the plurality of wires are independently energizable or energizable in groups. This may also be used to provide energy delivery in a monopolar fashion or it may be used to deliver energy in a bipolar fashion.

The energy delivery electrode1222may be utilized in this configuration to deliver energy. For example, the delivery electrode1222may be positioned within a lumen so as to deliver energy circumferentially to the inner surfaces of the lumen. Or the delivery electrode1222may be positioned against the opening of a lumen so that the distal face of the mesh basket delivers energy to the circumference of the opening of the lumen. In either case, the diameter of the delivery electrode1222may be chosen or adjusted to desirably fit the anatomy, such as the pulmonary vein of the specific patient, by controlling expansion of the mesh basket. In addition, the flexibility of the mesh basket allows the delivery electrode1222to adapt to a range of circular and non-circular shaped lumens or portions of the anatomy.

FIGS.31C-31Dillustrate further manipulation of the delivery electrode1222so as to move the delivery electrode1222into a partially inverted configuration. In some embodiments, this is achieved by further advancement of the additional shaft (i.e. beyond expansion of the mesh basket) so that the mesh basket begins to buckle as illustrated inFIG.31C. Further advancement, as illustrated inFIG.31Dpartially inverts the mesh basket so that the distal face of the mesh basket maintains a funnel shape while the proximal face of the mesh basket is inverted. Such inversion provides support for the distal face and assists in maintaining the funnel shape, particularly during placement against tissue and delivery of energy.

FIGS.32A-32Cillustrate an embodiment of a treatment catheter1302similar to that ofFIGS.31A-31D. The treatment catheter1302is again configured for one shot delivery rather than focal delivery. And, in this embodiment, the delivery electrode1322comprises a wire basket that is somewhat similar to the mesh basket ofFIGS.31A-31D. The wire basket has less surface area exposed to blood and therefore more efficient energy delivery. In some embodiments, the wire basket is comprised of a plurality of wires that are energizable in unison, such as to provide energy delivery in a monopolar fashion. It may be appreciated that portions of the wire basket may be insulated so as to focus energy delivery through particular uninsulated portions of the wire basket. This may also assist in reducing loss of energy to the surrounding blood environment. In other embodiments, the plurality of wires are independently energizable or energizable in groups. This may also be used to provide energy delivery in a monopolar fashion or it may be used to deliver energy in a bipolar fashion.

The treatment catheter1302is configured to move at least between a collapsed configuration, an expanded configuration and a partially inverted configuration.FIG.32Aillustrates the delivery electrode1322in a partially inverted configuration.FIG.32Billustrates the delivery electrode1322positioned against the opening of a lumen so that the distal face of the wire basket delivers energy to the circumference of the opening of the lumen.FIG.32Cillustrates the delivery electrode1322advanced into the lumen so that the distal face of the delivery electrode1322is positioned at least partially within the lumen.

Again, the diameter of the delivery electrode1322may be chosen or adjusted to desirably fit the anatomy, such as the pulmonary vein of the specific patient, by controlling expansion of the wire basket. In addition, the flexibility of the mesh basket allows the delivery electrode1322to adapt to a range of circular and non-circular shaped lumens or portions of the anatomy.

FIGS.33A-33Dillustrate an embodiment of a treatment catheter1402similar to that ofFIGS.31A-31DandFIGS.32A-32C. The treatment catheter1402is again configured for one shot delivery rather than focal delivery. And, in this embodiment, the delivery electrode1422comprises a wire basket that is somewhat similar to the mesh basket ofFIGS.31A-31Dand wire basket ofFIGS.32A-32C. Here, the wire basket has even less surface area exposed to blood and therefore provides more efficient energy delivery. This is achieved by the presence of legs or common supports1430on the distal and proximal faces of the wire basket, rather than woven wires. Since these portions typically align with the lumen, contact area is not needed and energy can be focused to the woven portion of the wire basket.

In some embodiments, the wire basket is comprised of a plurality of wires that are energizable in unison, such as to provide energy delivery in a monopolar fashion. It may be appreciated that portions of the wire basket may be insulated so as to focus energy delivery through particular uninsulated portions of the wire basket. This may also assist in reducing loss of energy to the surrounding blood environment. In other embodiments, the plurality of wires are independently energizable or energizable in groups. This may also be used to provide energy delivery in a monopolar fashion or it may be used to deliver energy in a bipolar fashion.

The treatment catheter1402is configured to move at least between a collapsed configuration, an expanded configuration and a flattened configuration.FIG.33Aillustrates the delivery electrode1422collapsed around the shaft1420upon which it is mounted so that it is able to be housed within a sheath (not shown).FIG.33Billustrates the delivery electrode1422in an expanded configuration. This may be achieved by retracting the sheath or advancing the shaft1420so as the reveal the wire basket. In some embodiments, the delivery electrode1422is self-expanding upon release from the sheath. In other embodiments, the wire basket is coupled with an additional shaft1435that is movable in relation to the shaft1420wherein advancement of the additional shaft1435draws the supports1430toward each other, expanding the wire basket.

The energy delivery electrode1422may be utilized in this configuration to deliver energy. For example, the delivery electrode1422may be positioned within a lumen so as to deliver energy circumferentially to the inner surfaces of the lumen. Or the delivery electrode1422may be positioned against the opening of a lumen so that the distal face of the wire basket delivers energy to the circumference of the opening of the lumen. In either case, the diameter of the delivery electrode1422may be chosen or adjusted to desirably fit the anatomy, such as the pulmonary vein of the specific patient, by controlling expansion of the wire basket. In addition, the flexibility of the wire basket allows the delivery electrode1422to adapt to a range of circular and non-circular shaped lumens or portions of the anatomy.

FIGS.33C-33Dillustrate further advancement of the additional shaft1435so as to move the delivery electrode1422into a flattened configuration. Here the supports1430are fully drawn together so as to flatten the wire basket therebetween substantially into a plane perpendicular to the shaft1420, as illustrated inFIG.33C.FIG.33Dprovides a perspective view of the configuration of the wire basket depicted inFIG.33C. Here it can be seen that the wire basket forms loops that extend radially outwardly away from the supports1430. The loops are able to deliver energy across a larger area than a single wire. The configuration of the loops are optimized to provide maximum coverage in an expanded position while still being able to be collapsed against the shaft for delivery through a small introducer lumen.

It may be appreciated that the delivery electrode1422may be positioned against the opening of a lumen, such as a pulmonary vein, such as in a manner as illustrated inFIG.32B. Likewise, the flexibility of the delivery electrode1422allows the delivery electrode1422to be advanced into the lumen so that the distal face of the delivery electrode1422is positioned at least partially within the lumen, such as in a manner as illustrated inFIG.32C.

FIGS.34-38,FIGS.39A-39Billustrate an embodiment of a treatment catheter1502configured for focal delivery. Here, the treatment catheter1502comprises a shaft1504having a distal end1506and an energy delivery body1522disposed near the distal end1506. Here, the energy delivery body1522comprises a plurality of conductive splines1524forming a convex distal face. In addition, in this embodiment, the energy delivery body1522includes a distal tip electrode1526. Here, the distal tip electrode1526is disposed along the center of the convex distal face. This provides additional energy delivery to the tissue upon which the convex distal face is positioned. This assists in avoiding any potential low or missing area of energy delivery, such as would generate a donut shaped lesion in the tissue. Thus, a continuous, circular lesion is created.

It may be appreciated that each spline1524may act as an electrode wherein the splines are energized in unison, independently or in groups. Thus, in some embodiments, the energy is delivered from all or a subset of the plurality of splines1524in unison so that the energy delivery body1522delivers energy in a monopolar fashion with the use of at least one remote return electrode. Likewise, the distal tip electrode1526may additionally be energized in unison with the splines1524so as to deliver energy is unison in a monopolar fashion. In other embodiments, the energy is delivered between selected splines or selected groups of splines so that the energy is delivered in a bipolar fashion. Likewise, combinations of one or more splines1524and the distal tip electrode1526may be energized to deliver energy in a bipolar fashion. Further, energy may be delivered from the tip electrode1526alone, without energy delivery from one or more splines1524, and vice versa wherein energy is delivered from one or more splines1524and not from the tip electrode1526. It may be appreciated that the splines1524may be wires, flat wires, struts, planks, strips or the like. In this embodiment, the splines1524are comprised of shape memory material, such as nitinol flat wire. In this embodiment, the nitinol flat wire has a platinum core for improved visualization under fluoroscopy. In this embodiment, the plurality of splines1522are partially covered by insulative material1528. Here, the insulative material1528is located on the proximal side of the energy delivery body1522so that energy conducted to the plurality of splines1524resists delivery through the insulative material1528, directing the energy to the uninsulated portion of the plurality of splines1522facing distally. Consequently, the energy provided to the energy delivery body1522is focused in the distal direction. Since the distal convex face is positionable against the target tissue area, the energy is efficiently directed toward the target tissue area without loss of energy out the proximal side of the energy delivery body1522. This conserves energy and reduces energy sink to surrounding blood, etc.

In this embodiment, the distal tip electrode1526is comprised of platinum-iridium and has a ball shape. It may be appreciated that other suitable materials may be used and other shapes may be used, such as a flat shape, oblong shape or a pointed shape, to name a few. In some embodiments, the distal tip electrode1526facilitates directing the treatment catheter1502to the target tissue area. This is achieved by using the distal tip electrode1526to detect areas of active cardiac tissue that are still needing to be treated. Thus, by reading the electrogram, the next placement of the catheter can be determined. In some embodiments, the distal tip electrode1526is used for recording data as will be described in later sections.

The energy delivery body1522is transitionable between a collapsed configuration and an expanded configuration.FIG.34illustrates the energy delivery body1522in an expanded configuration. To collapse the energy delivery body1522, a sheath or delivery tube is advanceable over the shaft1504in the distal direction. As the sheath is advanced over the energy delivery body1522, the flexibility of the splines1524allow the splines1524to straighten, thereby causing the profile of the energy delivery body1522to flatten and fit within the sheath. In addition, it may be appreciated that such straightening of the splines1524lengthens the distance between the distal tip electrode1526and the distal end1506of the shaft1504. For this reason, a tip electrode wire1530that conducts energy through the shaft1504to the distal tip electrode1526is slacked when the energy delivery body1522is in the expanded configuration as shown inFIG.34. Such slack allows for lengthening when in the collapsed configuration.

It may be appreciated that the catheter1504is delivered to the target treatment area within the body while the energy delivery body1522is collapsed and held within a sheath, sleeve or delivery device. Upon desired positioning in the body, the energy delivery body1522is then advanced from the sheath (or the sheath is retracted) so that the energy delivery body1522is exposed. Such exposure allows the energy delivery body1522to self-expand to the expanded configuration. It may be appreciated that in other embodiments, the energy delivery body1522may be expanded by other mechanism, such as by retraction of a plunger connected with the distal tip electrode1526or by expansion of a flexible expandable member (e.g., a balloon) within the energy delivery body1522. However, the embodiment ofFIG.34provides an energy delivery body1522that is free of a central shaft creating a hollow rounded cage. This allows for additional flexibility of the energy delivery body1522. For example, when pressing the convex distal face against target tissue, additional force may allow the plurality of splines1524to flex outwardly, increasing the diameter of the convex distal face. Likewise, movement of the shaft1504while keeping the convex distal face stationary, may allow increased force against the tissue in the direction of movement due to flexing of the splines1524. For example, movement of the shaft1504to the right during engagement may increase engagement of the splines1524on the right side of the convex distal face and allow more force against this area of the tissue. In addition, such increased flexibility may also allow the energy delivery body1522to be steered more easily, such as to bend more freely with the use of pullwires or the like.

FIG.35provides a side view of the embodiment of the treatment catheter1502ofFIG.34. Again, the plurality of splines1524are illustrated in an expanded configuration wherein the energy delivery body1522forms a ball-shaped cage having a convex distal face. In this embodiment, the plurality of splines1524come together, spaced around a shaft plug1532within the shaft1504, in an evenly spaced circumferential array. In this embodiment, each of the splines1524are connected to a conductive wire that extends through the shaft1504for connection with the energy generator. In this embodiment, the plurality of splines1524terminate around the distal tip electrode1526by curving and bending inward for mounting on a tip inner1534, as can be seen by referring back toFIG.34. Thus, in this embodiment, the splines1524are evenly spaced in a circumferential array around the tip inner1534. By curving and bending inward around the distal tip electrode1526, a smooth, distal face is formed for positioning against the target tissue.

In this embodiment, the energy delivery body1522includes a sensing electrode1540positioned within the energy delivery body1522so as to avoid contact with the target tissue. In this embodiment, the sensing electrode1540is disposed proximally of the distal tip electrode1526(i.e. behind the distal tip electrode1526) within the rounded cage of the plurality of splines1524. Here, the sensing electrode1540comprises a ring electrode, such as a single 0.030″ ring electrode, extending around the tip inner1534. In this embodiment, additional electrodes1542,1544are disposed along the shaft1504, such as two 0.070″ ring electrodes, proximal to the energy delivery body1522. In this embodiment, the electrodes1540,1542,1544are comprised of platinum-iridium and also serve as marker bands for visualization under fluroscopy.

The sensing electrode1540and the additional electrodes1542,1544are typically used for sensing ECG signals and also for providing information to an electroanatomic mapping system. For example, when sensing ECG signals, a user can verify or confirm location of the treatment catheter1502in the heart based on the sensed ECG signals. When approaching a ventricle, a user may verify such approach by checking that ventricular signals increase in amplitude. Likewise, in some instances, impedance measurements are tracked by the sensing electrode1540and/or the additional electrodes1542,1544. Electroanatomic mapping systems use such impedance measurements to visualize the location of these electrodes1540,1542,1544, and therefore the location of the treatment catheter1502, within the heart.

Referring toFIG.35, this embodiment also includes a steering mechanism. In this embodiment, the steering mechanism comprises a pullring1560disposed along the shaft1504. The pullring1560is connected with one or more pullwires. In this embodiment, the pullring1560is connected to a first pullwire1562aand a second pullwire1562b, wherein the pullwires1562a,1562bare attached to the pullring1560on opposite sides. The pullwires1562a,1562bextend toward the proximal end of the shaft1504so that the distal end1506can be manipulated remotely. Pulling of the first pullwire1562acauses the distal end1506and therefore energy delivery body1522to bend in the direction of the first pullwire1562a(e.g. to the left) and pulling of the second pullwire1562bcauses the distal end1506and therefore energy delivery body1522to bend in the direction of the second pullwire1562b(e.g. to the right). It may be appreciated that any suitable number of pullwires may be present to steer in a variety of directions. Likewise, other steering mechanisms may be used instead of or addition to the steering mechanisms described herein.

FIG.36illustrates a bottom view of the treatment catheter1502ofFIGS.34-35, facing the convex distal face of the energy delivery body1522. As illustrated, in this embodiment, the energy delivery body1522includes ten splines1524, however any suitable number of splines1524may be present including one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or more. Here, a distal portion of each spline1524extends radially outwardly from the distal tip electrode1526before curving back toward the proximal direction to form a ball, sphere or rounded cage shape. Thus, each of these spline surfaces are uninsulated and deliver energy to the tissue. In this embodiment, an angle θ forms between each spline1524, therefore each angle is 36 degrees. It may be appreciated that the angles θ will vary depending on the number of splines1524, however such angles θ are typically in a range of 10-45 degrees, such as 10-20 degrees, 20-30 degrees or 30-45 degrees. With fewer splines1524, such angles θ may increase to 50 degrees, 60 degrees, 70 degrees, 80 degrees or 90 degrees, to name a few.

FIG.37provides another perspective view of the embodiment ofFIG.34. In this view, irrigation ports1570are visible along the distal face of the shaft plug1532. The irrigation ports1570are so positioned so as to deliver irrigation fluid to a proximal end of the energy delivery body1522allowing flow toward a distal end of the energy delivery body1522(i.e. toward the tip inner1534and distal tip electrode1526). Such irrigation assists in reducing any potential blood clot formation along the energy delivery body1522. In some instances, blood clotting may be more likely between elements such as splines1524which are closely spaced and are positioned in a blood-filled field. As illustrated inFIG.37, the distance between the splines1524tapers toward the proximal end of the energy delivery body1522and toward the distal end of the energy delivery body1522. Such areas are more prone to blood clotting due to increased blood stagnation in these areas. Stagnant blood may clot causing risks to the patient. Using a flow of irrigation fluid, such as saline, in and around the splines1524decreases the likelihood of clots forming.

It may be appreciated that desired irrigation fluid flow would be sufficient to reach all or a majority of the potentially stagnant blood-filled areas around the splines1524. In some embodiments, this is achieved with the use of a plurality of irrigation ports1570that are configured to create turbulent flow within the hollow cage of the energy delivery body1522. Although a single irrigation lumen may provide a large enough output of fluid flow to reach the proximal end of the energy delivery body1522, the flow may not be strong enough to reach the distal end of the energy delivery body1522. However, having the single irrigation lumen pass fluid through multiple irrigation ports1570creates turbulence in the flow at the proximal end of the energy delivery body1522and the turbulent flow continues a wide fan of fluid flow through to the distal end of the energy delivery body1522. The wide fan also accounts for coverage of the energy delivery body1522when the energy delivery body1522has been bent or moved laterally during positioning or manipulation. It may be appreciated that such turbulent flow may also be achieve with the use of multiple irrigation lumens. Typically, the number of irrigation lumens is less than the number of irrigation ports so as to deliver adequate flow while creating turbulence.FIG.38provides a close-up illustration of a portion of the treatment catheter1502within the distal end1506of the shaft1504. Here, the shaft1504is removed to reveal the shaft plug1532with splines1524disposed therearound. Conduction wires1525are shown connected with each spline1525. The conduction wires1525extend along the shaft1504in the proximal direction for connection with the generator108so as to deliver the energy to the splines1525. The embodiment ofFIG.38includes two irrigation lumens1580that deliver fluid to the irrigation ports1570. Here, five irrigation ports1570are present. It may be appreciated that a variety of irrigation lumens1580may be present, including one, two, three, four, five, six or more. Likewise, a variety of irrigation ports1570may be present, including one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve or more. However, for turbulent flow, the irrigation ports1570typically outnumber the irrigation lumens1580.

FIGS.39A-39Bprovide additional illustrations of the embodiment ofFIG.34.FIG.39Aprovides an expanded illustration of elements comprising this embodiment of the treatment catheter1502. As shown, this embodiment includes a distal tip electrode1526, a tip inner1534, a tip electrode wire1530, an energy delivery body1522comprising a plurality of splines1524at least partially covered by insulative material1528, a retention band1590, a shaft plug1532, a solder plate1592, a glue potting1594, a pull-ring1560, an irrigation lumen1580, a shaft1504with electrodes1542,1544, and a shaft tip section1596.FIG.39Billustrates the treatment catheter1502ofFIG.39Ain its unexpanded state.

As mentioned previously, the treatment catheter1502is described as a focal therapy device designed to create lesions that are larger than the footprint of a solid tipped treatment catheter, such as illustrated inFIGS.2A-2B, yet smaller than the footprint of a one-shot device. In some embodiments, the shaft1504of the treatment catheter1502is 8 French (2.67 mm) and is delivered with the use of an 8.5 French (2.83 mm) sheath. In such embodiments, the energy delivery body1522is configured to fit within the 8.5 French sheath in its collapsed configuration, thus having an outer diameter of less than 2.83 mm. When the energy delivery body1522is released to its expanded state, the outer diameter typically expands to 8-15 mm which is 3-6 times the diameter of the shaft1504. It may be appreciated that the footprints of such devices may vary in size within this range including 8 mm, 9 mm, 10 mm, 11 mm, 12 mm, 13 mm, 14 mm, 15 mm, 8-10 mm, 9-10 mm, 9-15 mm, 10-15 mm, 12-15 mm, etc.

Sensors and Irrigation

The tissue modification systems100described herein deliver 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 which is inherent to all PEF therapies as it is a byproduct of energy deposition. However, acute, subacute, medium-, and long-term histological data all indicate that there are no substantial indication of thermal damage to the tissue using the systems, devices and methods described herein. Therefore, it is evident that thermal damage (extracellular protein denaturation) is not generated in the cardiac tissue, reducing the chances of adverse events and anatomical deficits such as pulmonary vein stenosis resulting from the treatment. This also eliminates the generation of surface char or thermal injury which impedes energy delivery to underlying tissue, reducing the ability to generate transmural lesions.

However, it may be appreciated that, in some embodiments, the system100includes temperature sensing and/or control measures for various purposes. In some embodiments, temperature is sensed and controlled to ensure that the temperature remains in the range of 30-65° C., 30-60° C., 30-55° C., 30-50° C., 30-45° C., 30-35° C. Thus, lesions are not created by thermal injury as the temperature of the tissue remains below a threshold for thermal ablation. In some embodiments, one or more temperature sensors are used to measure electrode and/or tissue temperature during treatment to ensure that energy deposited in the tissue does not result in any clinically significant tissue heating. For example, in some embodiments, a temperature sensor monitors the temperature of the tissue and/or electrode, and if a pre-defined threshold temperature is exceeded (e.g. 65° C.), the generator alters the algorithm to automatically cease energy delivery or modifies the algorithm to reduce temperature to below the pre-set threshold. For example, in some embodiments, if the temperature exceeds 65° C., the generator reduces the pulse width or increases the time between pulses and/or packets (e.g. delivering energy every other heart beat, every third heart beat, etc.) in an effort to reduce the temperature. This can occur in a pre-defined step-wise approach, as a percentage of the parameter, or by other methods. It may be appreciated that temperature sensors may be positioned on electrodes, adjacent to electrodes, or in any suitable location along the distal portion of the catheter. Alternatively or in addition, sensors may be positioned on one or more separate instruments.

In other embodiments, temperature is sensed to assess lesion formation. This may be particularly useful when generating lesions in anatomy having target tissue areas of differing thicknesses. A rapid rise in temperature indicates that the lesion has penetrated the depth of the tissue and is nearing completion. Sensing such changes in temperature may be particularly useful when generating lesions in thicker tissues or tissues of unknown depth.

In some embodiments, the treatment catheter includes irrigation to assist in controlling the temperature of the delivery electrode or surrounding tissue. In some instances, irrigation cools the delivery electrode, allowing more PEF delivery per time without increasing any potential heat-mediated damage. In some instances, irrigation also reduces or prevents coagulation near the tip of the catheter. It may be appreciated that irrigation may be activated, increased, reduced or halted based on information from one or more sensors, particularly one or more temperature sensors.

Such cooling is achieved by delivering fluid, such as isotonic saline solution, through a lumen in the catheter that exits through one or more irrigation ports along the distal end of the catheter. The fluid may be chilled fluid, room temperature fluid or warmed fluid. The fluid flow can be driven by a variety of mechanisms including a gravity driven drip, a peristaltic pump, a centrifugal pump, etc. In some embodiments, the irrigation has a flow rate of 0.1-10 ml/min, including 1 ml/min, 2 ml/min, 3 ml/min, 4 ml/min, 5 ml/min or more. In some embodiments, the flow rate is sensed by electrical or mechanical flow sensing mechanisms. In some embodiments, the temperature of the fluid is measured, and in other embodiments the temperature of the fluid is modified, such as warmed or cooled, as it is pumped into the treatment catheter, such as based on the measured temperature. In some embodiments, the fluid flow rate is determined based on the measured temperature of the tissue to be treated.

In some embodiments, the pump is in electrical communication with the generator108wherein the fluid flow rate is modified by the generator108based on the status of energy delivery to the treatment catheter102. For example, in some embodiments, fluid flow rate is increased during energy delivery. Likewise, in some embodiments, fluid flow rate is increased a predetermined amount to time prior to energy delivery and/or at a predetermined time(s) during energy delivery. Alternatively or in addition, fluid flow may be controlled on demand by the user. It may be appreciated that the pump may communicate with the generator108to operate at different speeds based on various aspects of the energy delivery algorithm152. In some embodiments, sensing of flowrate and communication with the generator108is used to prevent energy delivery if irrigation is not running. In other embodiments, selection of an energy delivery algorithm152in turn selects a fluid flow rate appropriate for the energy delivery algorithm152. In some embodiments, at least one irrigation port is located along an electrode and/or optionally at least one irrigation port is located along the shaft.

It may be appreciated that any of the catheter designs described herein may include one or more sensors (e.g. microsensors), such as impedance sensors, contact sensors, contact force sensors, electroanatomic mapping sensors, etc. Such sensors may be positioned on electrodes, adjacent to electrodes, or in any suitable location along the distal portion of the catheter. For example, microsensors may be located along one or more loops of a delivery electrode or along a support structure near the delivery electrode. Alternatively or in addition, sensors may be positioned on one or more separate instruments.

It may also be appreciated that although a variety of the delivery electrodes have been described as conductive wires capable of delivering energy therefrom, such designs may utilize individual electrodes (e.g. microelectrodes) spaced along a non-conductive wire. Optionally, such electrodes may be spaced along a conductive wire when the conductive wire is insulated from the electrodes where the electrodes are attached.