Apparatus, system, and method for ablating cardiac tissue

Abstract

To provide an irrigated ablation catheter.SOLUTION: There is provided an ablation catheter system for drug refractory symptomatic paroxysmal atrial fibrillation (PAF). The system can include an elongated body; an electrode assembly comprising a shell configured with an inner chamber and a wall defining a proximal portion and a distal portion, the wall of the distal portion having at least one aperture; and a micro-element extending through the inner chamber between the proximal portion and the distal portion, the micro-element having a distal end received in the at least one aperture, the distal end being at least coextensive with an outer surface of the wall. The system is configured to achieve acute procedural PVI success for all patients of a predetermined patient population suffering from PAF.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] (Cross - reference to related applications) This application is a continuation of U.S. Patent Application No. 12 / 969,684, filed on December 16, 2010, which is the current U.S. Patent No. 9,737,353, issued on August 22, 2017; a continuation of U.S. Patent Application No. 15 / 682,445, filed on August 21, 2017, which is the current U.S. Patent No. 9,993,285, issued on June 12, 2018; a continuation of U.S. Patent Application No. 16 / 005,585, filed on June 11, 2018, which is the current U.S. Patent No. 10,206,733, issued on February 19, 2019; U.S. Patent Application No. 16 / 227,809, filed on February 15, 2019; a divisional application of U.S. Patent Application No. 14 / 058,325, filed on October 21, 2013, which is the current U.S. Patent No. 9,980,652, issued on May 29, 2018; U.S. Patent Application No. 15 / 966,662, filed on April 30, 2018; a divisional application of U.S. Patent Application No. 14 / 886,761, filed on October 19, 2015, which is the current U.S. Patent No. 10,213,856, issued on February 26, 2019; U.S. Patent Application No. 16 / 255,729, filed on January 23, 2019; a divisional application of U.S. Patent Application No. 14 / 279,682, filed on May 16, 2014, which is the current U.S. Patent No. 10,517,667, issued on December 31, 2019; U.S. Patent Application No. 16 / 716,159, filed on December 16, 2019; claiming priority to U.S. Patent Application No. 62 / 286,534, filed on January 25, 2016, which is the current U.S. Patent No. 10,405,920, issued on September 10, 2019; a continuation of U.S. Patent Application No. 15 / 179,090, filed on June 10, 2016; U.S. Patent Application No. 16 / 565,187, filed on September 9, 2019; claiming priority to U.S. Patent Application No. 62 / 286,534, filed on January 25, 2016, which is the current U.S. Patent No. 10,292,763, issued on May 21, 2019; a continuation of U.S. Patent Application No. 15 / 179,129, filed on June 10, 2016; which is the current U.S. Patent No. 10,463,428, issued on November 5, 2019; a continuation of U.S. Patent Application No. 16 / 396,246, filed on April 26, 2019; U.S. Patent Application No. 16 / 592,671, filed on October 3, 2019;This is a continuation-in-part application of U.S. Patent Application No. 16 / 599,924, filed on October 11, 2019, which is a continuation of U.S. Patent Application No. 15 / 179,167, filed on June 10, 2016, which claims priority to U.S. Patent Application No. 62 / 286,534, filed on January 25, 2016, and issued as U.S. Patent No. 10,441,354 on October 15, 2019. This application also claims priority to U.S. Provisional Patent Application No. 62 / 843,213, filed on May 3, 2019, and U.S. Provisional Patent Application No. 62 / 892,464, filed on August 27, 2019. Their contents are hereby incorporated by reference in their entirety as if set forth verbatim.;

[0002] (Field of the Invention) The present disclosure generally relates to methods and devices for invasive medical procedures, and more particularly to catheters, and specifically to infusion ablation catheters.

Background Art

[0003] Ablation of myocardial tissue is well known as a treatment for cardiac arrhythmias. For example, in radiofrequency (RF) ablation, a catheter is inserted into the heart and brought into contact with tissue at a target location. Then, RF energy is applied to the catheter via an electrode to create lesions for the purpose of disrupting arrhythmogenic electrical current pathways within the tissue.

[0004] Irrigation catheters are currently commonly used in ablation procedures. Irrigation provides many advantages, such as cooling the electrodes and tissue, which can prevent overheating of the tissue that could otherwise cause carbonization, clot formation, and even steam bursts if cooling is not performed. However, since tissue temperature is evaluated during ablation procedures to prevent such adverse events, it is important that the detected temperature accurately reflects the tissue temperature and does not reflect only the surface temperature of the tissue, which may be biased by the cooling irrigation fluid from the catheter. Furthermore, generally, more accurate thermal and electrical indicators, such as improved impedance measurements for purposes such as determining the size of the lesion, are provided by contact with deeper tissues.

[0005] Therefore, there is a need for an irrigation ablation catheter with a distal end that can more effectively probe tissue without significantly damaging or fracturing the tissue in order to perform more accurate measurements such as temperature sensing and impedance measurement.

[0006] Furthermore, even in the initial treatment, the pathophysiology of persistent atrial fibrillation (PAF) can be complex and often involves multiple triggers outside the pulmonary vein region, making their identification and treatment difficult. Numerous studies have demonstrated that the success rate of pulmonary vein isolation (PVI) is lower in patients with persistent PAF. Atrial fibrillation (AF) is the most common persistent arrhythmia in humans. AF affects approximately 0.4% to 1% of the general population, with a prevalence that increases with age from <1% in young adults to 8% in patients over 80 years old. Radiofrequency (RF) catheter ablation has produced excellent results in treating many types of ventricular arrhythmias. Its usefulness in the treatment of paroxysmal AF has already been established, and studies have shown a high rate of arrhythmia disappearance. In a non-randomized clinical trial evaluating the effect of contact force on successful outcomes, RF ablation with the THERMOCOOL SMARTTOUCH® SF catheter was associated with elimination of symptomatic atrial arrhythmias in 72.5% of patients at 1 year.

[0007] The 2017 EHRA / ECAS / APHRS / SOLAECE Consensus Statement states that electrical isolation of the pulmonary veins (PVs) from the left atrium is "the basis for the majority of AF ablation procedures." The aim of PV isolation (PVI) is to create a transmural, continuous, and durable RF lesion. The conventional parameters of RF ablation using an irrigated catheter are related to delivering moderate power (20 - 40 W) over a relatively long duration (20 - 40 seconds) in a contact force range of 10 - 20 grams. Still, the occurrence of acute PV reconnection is frequent, occurring at a frequency of 15 - 22% after PVI. The mechanisms underlying PV reconnection are not fully understood, but catheter instability, tissue edema, and reversible non-transmural damage have been suggested as the main causes.

[0008] RF lesion formation results from two thermal heating phases, namely, resistive heating and conductive heating. Resistive heating strongly depends on the RF power that immediately generates a hot spot approximately 2 mm from the tip. This resistive heating phase creates a heat source that passively extends to deeper tissue layers during the conductive heating phase. Conductive heating is time-dependent, and heat is transferred from the hot spot to deeper layers of the myocardium.

[0009] Modifying the relationship between the resistive heating phase and the conductive heating phase by increasing the resistive heating phase to immediately deliver heat to the full thickness of the LA tissue around the PVs could achieve a uniform transmural lesion. By reducing the conductive heating phase, associated tissue damage can be limited. This can be achieved by delivering a large current over a short duration. Therefore, an ablation catheter that solves these and other problems in the art is desired. Summary of the Invention Means for Solving the Problems

[0010] In some embodiments, an ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system comprises a shell configured with an elongated body and a wall defining an inner chamber and proximal and distal portions, the wall of the distal portion having at least one opening, an electrode assembly, and a microelement extending through the inner chamber between the proximal and distal portions and having a distal end received within at least one opening, the distal end having at least the same extent as the outer surface of the wall. This system is configured to achieve acute procedural PVI success for all patients in a given patient population suffering from PAF.

[0011] In some embodiments, an ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system comprises a shell configured with an elongated body and a wall defining an inner chamber and proximal and distal portions, the wall of the distal portion having at least one opening, an electrode assembly, and a microelement extending through the inner chamber between the proximal and distal portions and having a distal end received within at least one opening, the distal end having at least the same extent as the outer surface of the wall. This system is configured to clinically improve all fluids delivered via an intravenous line between PAF and RF ablation by the ablation catheter system.

[0012] In some embodiments, an ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system comprises an electrode assembly comprising a shell configured with an elongate body, an inner chamber, and a wall defining a proximal portion and a distal portion, the wall of the distal portion having at least one opening, and a micro - element extending through the inner chamber between the proximal portion and the distal portion and having a distal end received within at least one opening, the distal end having at least the same extent as the outer surface of the wall. The system is configured to clinically improve safety and efficacy, and as a result, the RF ablation time is at least about 80% less than the ablation time of previously clinically approved catheter systems for treating PAF.

[0013] In some embodiments, an ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system comprises an electrode assembly comprising a shell configured with an elongate body, an inner chamber, and a wall defining a proximal portion and a distal portion, the wall of the distal portion having at least one opening, and a micro - element extending through the inner chamber between the proximal portion and the distal portion and having a distal end received within at least one opening, the distal end having at least the same extent as the outer surface of the wall, and an irrigation pump configured to deliver a continuous infusion of a treatment solution at about 2 milliliters per minute by the elongate body and through the elongate body when RF energy is not being delivered during RF ablation. The system is configured to clinically improve the safety and efficacy of PAF by a contact force acting in the range of about 5 - 30 g between the catheter system and the target site.

[0014] In some embodiments, an ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system includes an electrode assembly comprising a shell configured with an elongated body, an inner chamber, and a wall defining a proximal portion and a distal portion, wherein the wall of the distal portion has at least one opening; a microelement extending through the inner chamber between the proximal portion and the distal portion and having a distal end received within at least one opening, the distal end having at least the same spread as the outer surface of the wall; and a perfusion pump configured to deliver a continuous infusion of a therapeutic solution at about 2 milliliters per minute by and through the elongated body when RF energy is not being delivered between the microelement and RF ablation. The system is configured to clinically improve the safety and efficacy of PAF by significantly shorter total treatment times, ablation times, fluoroscopy times, and RF application times.

[0015] In some embodiments, an ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system includes an electrode assembly comprising a shell configured with an elongated body, an inner chamber, and a wall defining a proximal portion and a distal portion, wherein the wall of the distal portion has at least one opening; a microelement extending through the inner chamber between the proximal portion and the distal portion and having a distal end received within at least one opening, the distal end having at least the same spread as the outer surface of the wall; and a perfusion pump configured to deliver a continuous infusion of a therapeutic solution at about 2 milliliters per minute by and through the elongated body when RF energy is not being delivered between the microelement and RF ablation. The system is configured to achieve zero occurrence of steam pops in both left - atrial ablation and right - atrial ablation using the ablation catheter system at a given perfusion flow rate and a power setting including 90W.

[0016] In some embodiments, the system is configured to clinically improve the treatment of complex cardiac arrhythmias.

[0017] In some embodiments, the size of a given patient population is at least about 50 patients.

[0018] In some embodiments, the system includes an infusion pump for delivering a treatment solution to a treatment site through a catheter system.

[0019] In some embodiments, the system includes a force sensing system for detecting a contact force applied to a treatment site by a catheter system during use.

[0020] In some embodiments, the system is configured for use only in ablation procedures that use an infusion flow and maintain a flow rate of 8 milliliters per minute.

[0021] In some embodiments, clinical safety is defined by the percentage of subjects having any primary adverse event (PAE) occurring within 7 days of an ablation procedure.

[0022] In some embodiments, the clinical efficacy endpoint is defined by the percentage of subjects having no recorded atrial arrhythmia (atrial fibrillation (AF)) episodes for at least about 9 months at 12 months after an ablation procedure.

[0023] In some embodiments, the clinical efficacy endpoint is defined by the percentage of subjects having no recorded atrial tachycardia (AT) episodes for at least about 9 months at 12 months after an ablation procedure.

[0024] In some embodiments, the clinical efficacy endpoint is defined by the percentage of subjects having no recorded atrial flutter (AFL) episodes for at least about 9 months at 12 months after an ablation procedure.

[0025] In some embodiments, clinical safety is defined by the percentage of subjects having a primary adverse event within about 7 days from the ablation procedure.

[0026] In some embodiments, the catheter system is configured to reduce the incidence of serious adverse events for a given patient population during and after ablation of the catheter system, and for up to 3 months after the procedure.

[0027] In some embodiments, the catheter system is configured to clinically improve the success rate of the acute procedure as defined by the percentage of subjects having electrical isolation of the PV at the end of the procedure.

[0028] In some embodiments, the catheter system is configured to clinically improve the success rate of the acute procedure as defined by the percentage of subjects having electrical isolation of the PV using only the ablation mode.

[0029] In some embodiments, the ablation mode is about 90 W at a flow rate of 8 milliliters per minute.

[0030] In some embodiments, the ablation mode exceeds at least about 50 W at a flow rate of 8 milliliters per minute.

[0031] In some embodiments, the ablation mode is about 90 W using an RF generator for a duration of at least about 4 seconds.

[0032] In some embodiments, the catheter system is configured to clinically improve the effectiveness defined by the combination of the percentage of subjects having electrical isolation of the PV at all power settings and the percentage of subjects having electrical isolation of the PV after the first pass isolation.

[0033] In some embodiments, the catheter system is configured to clinically improve the effectiveness defined by combining the percentage of subjects having electrical isolation of the PV at all power settings with the percentage of subjects having electrical isolation of the PV after a waiting period.

[0034] In some embodiments, the catheter system is configured to clinically improve the effectiveness defined by combining the percentage of subjects having electrical isolation of the PV at all power settings with the percentage of subjects having electrical isolation of the PV after adenosine loading.

[0035] In some embodiments, the catheter system is configured to clinically improve the effectiveness defined by the percentage of subjects and the percentage of PVs having touch-ups to exclude ablation of acute reconnection among all target veins and touch-up positions.

[0036] In some embodiments, the catheter system is configured to clinically improve the effectiveness defined by the percentage of subjects having the anatomical location of acute PV reconnection after the first enclosure.

[0037] In some embodiments, the catheter system is configured to clinically improve the incidence rate of unexpected harmful device effects during and following the ablation procedure used with the catheter system.

[0038] In some embodiments, the catheter system is configured to clinically improve the incidence rate of serious adverse events and the incidence rate of hemorrhagic complications within 7 days after the ablation procedure performed by the catheter system.

[0039] In some embodiments, the catheter system is configured to clinically improve the incidence rate of serious adverse events and the incidence rate of hemorrhagic complications 7 to 30 days after the ablation procedure performed by the catheter system.

[0040] In some embodiments, the catheter system is configured to clinically improve the incidence rate of serious adverse events and the incidence rate of hemorrhagic complications at least 30 days after an ablation procedure performed by the catheter system.

[0041] In some embodiments, the incidence rate of hemorrhagic complications is defined as major bleeding.

[0042] In some embodiments, the incidence rate of hemorrhagic complications is defined as clinically relevant non-major bleeding.

[0043] In some embodiments, the incidence rate of hemorrhagic complications is defined as minor bleeding.

[0044] In some embodiments, the catheter system is configured to clinically improve the coagulation rate associated with RF ablation of the catheter system for a predetermined patient population.

[0045] In some embodiments, the catheter system is configured to clinically improve the steam pop rate compared to a previously clinically approved ablation catheter for a predetermined patient population.

[0046] In some embodiments, a conventional clinically approved ablation catheter is configured to perform RF ablation at about 50 W or less at a flow rate of 8 milliliters per minute, and the present catheter system is configured to perform RF ablation at about 90 W at a flow rate of 8 milliliters per minute.

[0047] In some embodiments, the catheter system is configured to clinically improve the lesion dimensions including the maximum depth, maximum diameter, and surface diameter compared to a previously clinically approved ablation catheter for a predetermined patient population.

[0048] In some embodiments, the catheter system is configured to clinically improve the average power used during ablation for a given patient population as compared to a previously clinically approved ablation catheter.

[0049] In some embodiments, the catheter system is configured to clinically improve the maximum electrode temperature used during ablation for a given patient population as compared to a previously clinically approved ablation catheter.

[0050] In some embodiments, the catheter system is configured to clinically improve the impedance drop during ablation for a given patient population as compared to a previously clinically approved ablation catheter.

[0051] In some embodiments, the catheter system is configured to clinically improve RF energy delivery at the target site.

[0052] In some embodiments, the catheter system is configured to clinically improve acute isolation of the pulmonary veins.

[0053] In some embodiments, the catheter system is configured to clinically improve the pacing from the ring electrode and the microelectrodes during the idle state and during RF ablation.

[0054] In some embodiments, the catheter system is configured to clinically improve the temperature feedback during ablation as compared to a previously clinically approved ablation catheter.

[0055] In some embodiments, the chamber is adapted to receive fluid and the chamber has a plurality of irrigation apertures configured to flow the fluid from the inside of the chamber to the outside of the chamber.

[0056] In some embodiments, the distal end of the microelement includes a portion exposed outside the wall of the shell.

[0057] In some embodiments, the microelement has a microelectrode element at its distal end, and at least one wire is attached to the microelectrode element.

[0058] In some embodiments, the microelement is configured for temperature sensing.

[0059] In some embodiments, the system includes a plurality of microelements each having a distal end, and the distal ends of the microelements are arranged in a radial pattern on the distal portion of the electrode about the longitudinal axis of the electrode.

[0060] In some embodiments, the plurality is in the range of about 2 to 6.

[0061] In some embodiments, the plurality is 6.

[0062] In some embodiments, the system includes a first plurality of first microelements configured for impedance sensing and a second plurality of second microelements configured for temperature sensing.

[0063] In some embodiments, the distal ends of the first microelements are arranged in a radial pattern along the outer periphery of the distal portion of the shell about the longitudinal axis of the electrode.

[0064] In some embodiments, the distal ends of the second microelements are also arranged in a radial pattern along the outer periphery with a spacing from the first microelements.

[0065] In some embodiments, the distal ends of the second microelements are arranged in a radial pattern along a different outer periphery of the distal portion of the shell about the longitudinal axis of the electrode.

[0066] In some embodiments, the exposed portion extends at an angle having a distal component and a radial component with respect to the longitudinal axis of the electrode.

[0067] In some embodiments, the exposed portion has a non-invasive form adapted to form micro-indentations in the tissue without tearing the tissue.

[0068] In some embodiments, the system is configured to implement a method that includes selectively positioning a diagnostic catheter at a treatment site within a vasculature, selectively positioning an ablation catheter system at the treatment site according to any of the preceding claims, performing PVI by ablating tissue at the treatment site using the ablation catheter system, and clinically improving all fluids delivered via an intravenous line by the ablation catheter system during an ablation procedure by the ablation catheter system.

[0069] In some embodiments, the system is configured to implement a method that includes inserting an ablation catheter system according to any of the preceding claims into a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor in proximity within the body, ablating the cardiac tissue using the ablation catheter system, and achieving complete pulmonary vein isolation by the ablation catheter system for all patients in a given patient population suffering from PAF.

[0070] In some embodiments, the system comprises inserting an ablation catheter system into the body of a living being in accordance with any of the preceding claims, urging the ablation catheter system to contact the heart tissue within the body, generating ablation energy at a power output level at a certain current level, transmitting the generated energy into the tissue via the ablation catheter system, ablating the heart tissue using the ablation catheter system, and clinically improving safety and efficacy by the ablation catheter system, such that, as a result, the RF ablation time is reduced by at least about 80% compared to the ablation time of previously clinically approved catheter systems for treating PAF, and improving.

[0071] In some embodiments, the system comprises selectively positioning a diagnostic catheter at a treatment site within a vasculature, selectively positioning an ablation catheter system at the treatment site in accordance with any of the preceding claims, performing PVI by ablating tissue at the treatment site using the ablation catheter system, and clinically improving the safety and efficacy of PAF by a contact force acting in the range of about 5 to 30 grams between the ablation catheter system and the target site by the ablation catheter system.

[0072] In some embodiments, the system comprises inserting an ablation catheter system in accordance with any of the preceding claims into a treatment site including heart tissue, the system including at least one electrode and at least one sensor proximally within the body, inserting, ablating the heart tissue using the ablation catheter system, and achieving clinically improved safety and efficacy of PAF by a significantly shorter total treatment time, ablation time, fluoroscopy time, and high-frequency application time.

[0073] In some embodiments, the system includes inserting an ablation catheter system into a living body's body in accordance with any of the previous claims, urging the ablation catheter system to contact the heart tissue within the body, generating ablation energy at a power output level at a certain current level, transmitting the generated energy into the tissue via the ablation catheter system, ablating the heart tissue using the ablation catheter system, and achieving zero occurrence of steam pop in both left atrial ablation and right atrial ablation using the ablation catheter system at a power setting including a predetermined perfusion flow rate and 90 W.

[0074] In some embodiments, a method for performing clinically improved cardiac ablation is disclosed, the method including selectively positioning a diagnostic catheter at a treatment site within a vascular structure, selectively positioning an ablation catheter system at the treatment site in accordance with any of the previous claims, performing PVI by ablating tissue at the treatment site using the ablation catheter system, and clinically improving all fluids delivered via an intravenous line by the ablation catheter system during the ablation procedure.

[0075] In some embodiments, a method for performing RF ablation on cardiac tissue during a pulmonary vein isolation procedure is disclosed, the method comprising inserting into a treatment site comprising cardiac tissue an ablation catheter system according to any of the preceding claims, the system comprising at least one electrode and at least one sensor proximate to the body within the body, inserting, ablating the cardiac tissue using the ablation catheter system, and achieving complete pulmonary vein isolation by the ablation catheter system for all patients in a given patient population suffering from PAF.

[0076] In some embodiments, a method for performing RF ablation on cardiac tissue during a pulmonary vein isolation procedure is disclosed, the method comprising inserting into the body of a living being an ablation catheter system according to any of the preceding claims, actuating the ablation catheter system to contact cardiac tissue within the body, generating ablation energy at a power output level at a certain current level, transmitting the generated energy into the tissue via the ablation catheter system, ablating the cardiac tissue using the ablation catheter system, and clinically improving safety and efficacy by the ablation catheter system, such that as a result, the RF ablation time is at least about 80% less than the ablation time of previously clinically approved catheter systems for treating PAF.

[0077] In some embodiments, a method for performing clinically improved cardiac ablation is disclosed, the method comprising selectively positioning a diagnostic catheter at a treatment site within a vasculature; selectively positioning, at the treatment site, an ablation catheter system according to any of the previous claims; performing PVI by ablating tissue at the treatment site using the ablation catheter system; and clinically improving the safety and efficacy of PAF by the ablation catheter system with a contact force acting in the range of about 5 to 30 grams between the ablation catheter system and the target site.

[0078] In some embodiments, a method for performing RF ablation on cardiac tissue during a pulmonary vein isolation procedure is disclosed, the method comprising inserting, into a treatment site containing cardiac tissue, an ablation catheter system according to any of the previous claims, the system comprising at least one electrode and at least one sensor proximate to and within the body; ablating the cardiac tissue using the ablation catheter system; and achieving clinically improved safety and efficacy of PAF with a significantly shorter total procedure time, ablation time, fluoroscopy time, and RF application time.

[0079] In some embodiments, a method for performing RF ablation on cardiac tissue during a pulmonary vein isolation procedure is disclosed, the method comprising inserting into the body of a living being an ablation catheter system according to any of the preceding claims, actuating the ablation catheter system to contact the cardiac tissue within the body, generating ablation energy at a power output level at a certain current level, transmitting the generated energy into the tissue via the ablation catheter system, ablating the cardiac tissue using the ablation catheter system, and achieving zero occurrence of steam pop in both left atrial ablation and right atrial ablation using the ablation catheter system at a power setting including a predetermined irrigation flow rate and 90W.

[0080] In some embodiments, for a target temperature of 50°C and an ablation duration of 4 seconds, the achieving step further comprises applying an average force of about 7.5 grams to the cardiac tissue by the ablation catheter system during use.

[0081] In some embodiments, for a target temperature of 55°C and an ablation duration of 4 seconds, the achieving step further comprises applying an average force of about 9.1 grams to the cardiac tissue by the ablation catheter system during use.

[0082] In some embodiments, for a target temperature of 60°C and an ablation duration of 4 seconds, the achieving step further comprises applying an average force of about 17.7 grams to the cardiac tissue by the ablation catheter system during use.

[0083] In some embodiments, for a target temperature of 60°C and an ablation duration of 2 seconds, the achieving step further comprises applying an average force of about 13.6 grams to the cardiac tissue by the ablation catheter system during use.

[0084] In some embodiments, the diseased heart is the treatment site of the method.

[0085] In some embodiments, the method includes clinically improving effective electrogram signal attenuation and making the lesion clinically equivalent or better in all four ventricles as compared to a previously clinically approved ablation catheter system.

[0086] In some embodiments, the method includes clinically reducing by about 76.5% the total fluid delivered to the treatment site by an ablation catheter system during cardiac ablation as compared to a previously clinically approved ablation catheter system.

[0087] In some embodiments, the method includes delivering by an ablation catheter system no more than about 382 mL of treatment fluid to the treatment site during an ablation procedure.

[0088] In some embodiments, the method includes clinically reducing by about 50% the total ablation procedure time by an ablation catheter system as compared to a previously clinically approved ablation catheter system.

[0089] In some embodiments, the method includes clinically making the total ablation procedure time by an ablation catheter system no more than about 105.2 minutes.

[0090] In some embodiments, the method includes clinically reducing by about 62% the total ablation time by an ablation catheter system as compared to a previously clinically approved ablation catheter system.

[0091] In some embodiments, the method includes clinically making the total ablation time by an ablation catheter system no more than about 46 minutes.

[0092] In some embodiments, the method includes clinically reducing the total fluoroscopy time of the ablation catheter system by about 80% from a previously clinically approved ablation catheter system.

[0093] In some embodiments, the method includes clinically reducing the total fluoroscopy time by the ablation catheter system to about 6.6 minutes or less.

[0094] In some embodiments, the method includes clinically reducing the total RF application duration of the ablation catheter system by about 83% from a previously clinically approved ablation catheter system.

[0095] In some embodiments, the method includes clinically reducing the total RF application duration by the ablation catheter system to about 8.1 minutes or less.

[0096] In some embodiments, the total treatment time and fluoroscopy time of the ablation catheter system include about 105 minutes and 6.6 minutes, respectively.

[0097] In some embodiments, the method includes placing an esophageal temperature monitoring device and using the temperature monitoring device to monitor the esophageal temperature.

[0098] In some embodiments, the method includes confirming the ACT more than 350 seconds before inserting the ablation catheter system into the left atrium and maintaining it throughout the procedure.

[0099] In some embodiments, the method includes generating an anatomical map of the left atrium before an ablation procedure in the LA.

[0100] In some embodiments, the method includes using an ablation pre-flow delay of at least 2 seconds before RF application.

[0101] In some embodiments, the method includes RF ablation via application of up to 90 W of RF power for up to 4 seconds.

[0102] In some embodiments, the method includes moving an ablation catheter system from a first position of a treatment site to a second position of the treatment site.

[0103] In some embodiments, the step of moving the ablation catheter system includes moving the ablation catheter system by about 4 millimeters when a clinically effective ablation has been achieved.

[0104] In some embodiments, the step of moving the ablation catheter system includes moving the ablation catheter system substantially when a clinically effective ablation has been achieved within 20 seconds as determined by reduction of the electrogram and / or decrease in impedance.

[0105] In some embodiments, the method includes performing ablation of the left atrium and real-time PV isolation using an ablation catheter system.

[0106] In some embodiments, the method includes confirming entry block at all target PVS using a diagnostic catheter.

[0107] In some embodiments, the method includes visualizing a treatment site and an ablation catheter system using fluoroscopy.

[0108] In some embodiments, the method is to minimize the risk of esophageal injury by using an esophageal temperature probe, where a temperature increase is detected within the esophagus and then the tissue at the treatment site is cooled to a predetermined temperature, and includes visualizing the esophagus under fluoroscopy.

[0109] In some embodiments, the ablation duration did not exceed 30 seconds on the posterior wall at the treatment site.

[0110] In some embodiments, the method includes clinically reducing the PVI ablation time of the ablation catheter system between the first RF application and the last RF application to the PV before confirmation of isolation and achievement of circumferential ablation as compared to a previous clinically approved ablation catheter system.

[0111] In some embodiments, the method includes clinically reducing the subject PVI ablation time of the ablation catheter system between the first RF application and the last RF application before all PVIs are completed as compared to a previous clinically approved ablation catheter system.

[0112] In some embodiments, the method includes clinically reducing the total ablation time of the ablation catheter system between the first RF application and the last RF application before all PVIs are completed as compared to a previous clinically approved ablation catheter system.

[0113] In some embodiments, the total ablation time is determined by the total procedure time from the first femoral puncture to the removal of the last catheter.

[0114] In some embodiments, the method includes clinically improving the ablation parameters of the ablation catheter system during the ablation procedure as compared to a previous clinically approved ablation catheter system, including temperature, impedance, power, contact force, and RF duration.

[0115] In some embodiments, the method includes clinically improving the atrial mapping time.

[0116] In some embodiments, the method includes clinically improving the LA catheter dwell time from LA insertion of the ablation catheter to LA removal of the ablation catheter.

[0117] In some embodiments, the method includes perfusing cardiac tissue via an ablation catheter system.

[0118] In some embodiments, the method includes minimizing acute or minimal subendocardial hemorrhage in the ventricles and mitral valve by using an ablation catheter system in eliminating or alleviating persistent atrial fibrillation.

[0119] In some embodiments, the method includes demonstrating that the safety and / or effectiveness of an ablation catheter system for patients in a predetermined patient population is clinically improved, the predetermined patient population being divided into three different arrhythmia subgroups, namely ventricular tachycardia, complex atrial tachycardia or recurrent paroxysmal atrial fibrillation, and persistent atrial fibrillation.

[0120] In some embodiments, the method includes clinically improving the safety and effectiveness of an ablation catheter system for at least one of the left atrium, right atrium, left ventricle, and right ventricle.

[0121] In some embodiments, a method of using an ablation catheter system is disclosed, the method including selectively positioning a diagnostic catheter at a treatment site within a vasculature, selectively positioning an ablation catheter system at the treatment site according to any of the preceding claims, performing PVI by ablating tissue at the treatment site using the ablation catheter system, and clinically improving all fluids delivered via an intravenous line by the ablation catheter system during an ablation procedure by the ablation catheter system.

[0122] In some embodiments, a method of using an ablation catheter system is disclosed, the method including inserting an ablation catheter system according to any of the preceding claims into a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor proximate to the body within the body; ablating cardiac tissue using the ablation catheter system; and achieving complete pulmonary vein isolation by the ablation catheter system for all patients in a given patient population suffering from PAF.

[0123] In some embodiments, a method of using an ablation catheter system is disclosed, the method including inserting an ablation catheter system according to any of the preceding claims into a living body; actuating the ablation catheter system to contact cardiac tissue within the body; generating ablation energy at a power output level at a certain current level; transmitting the generated energy into the tissue via the ablation catheter system; ablating cardiac tissue using the ablation catheter system; and clinically improving safety and efficacy by the ablation catheter system, such that, as a result, the RF ablation time is at least about 80% less than the ablation time of previously clinically approved catheter systems for treating PAF.

[0124] In some embodiments, methods of using an ablation catheter system are disclosed, the methods including selectively positioning a diagnostic catheter at a treatment site within a vasculature, selectively positioning an ablation catheter system at the treatment site according to any of the previous claims, performing PVI by ablating tissue at the treatment site using the ablation catheter system, and clinically improving the safety and efficacy of PAF by a contact force acting in the range of about 5 to 30 grams between the ablation catheter system and the target site by the ablation catheter system.

[0125] In some embodiments, methods of using an ablation catheter system are disclosed, the methods including inserting an ablation catheter system according to any of the previous claims into a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor proximate to the body interior, ablating cardiac tissue using the ablation catheter system, and achieving clinically improved safety and efficacy of PAF by a significantly shorter total treatment time, ablation time, fluoroscopy time, and high-frequency application time.

[0126] In some embodiments, a method of using an ablation catheter system is disclosed, the method including inserting an ablation catheter system according to any of the preceding claims into a body of a living being, urging the ablation catheter system to contact cardiac tissue within the body, generating ablation energy at a power output level at a certain current level, transmitting the generated energy into the tissue via the ablation catheter system, ablating the cardiac tissue using the ablation catheter system, and achieving zero occurrence of steam pop in both left atrial ablation and right atrial ablation using the ablation catheter system at a power setting including a predetermined perfusion flow rate and 90 W.

[0127] In some embodiments, for a target temperature of 50° C. and an ablation duration of 4 seconds, the achieving step further includes applying an average force of about 7.5 grams to the cardiac tissue by the ablation catheter system during use.

[0128] In some embodiments, for a target temperature of 55° C. and an ablation duration of 4 seconds, the achieving step further includes applying an average force of about 9.1 grams to the cardiac tissue by the ablation catheter system during use.

[0129] In some embodiments, for a target temperature of 60° C. and an ablation duration of 4 seconds, the achieving step further includes applying an average force of about 17.7 grams to the cardiac tissue by the ablation catheter system during use.

[0130] In some embodiments, for a target temperature of 60° C. and an ablation duration of 2 seconds, the achieving step further includes applying an average force of about 13.6 grams to the cardiac tissue by the ablation catheter system during use.

[0131] In some embodiments, the diseased heart is the treatment site of the method.

[0132] In some embodiments, the present method of use includes clinically improving effective electrogram signal attenuation and making the lesion clinically equivalent or better in all four ventricles as compared to previous clinically approved ablation catheter systems.

[0133] In some embodiments, the present method of use includes clinically reducing by about 76.5% the total fluid delivered to the treatment site by the ablation catheter system during cardiac ablation as compared to previous clinically approved ablation catheter systems.

[0134] In some embodiments, the present method of use includes delivering by the ablation catheter system up to about 382 mL of treatment fluid to the treatment site during an ablation procedure.

[0135] In some embodiments, the present method of use includes clinically reducing by about 50% the total ablation procedure time by the ablation catheter system as compared to previous clinically approved ablation catheter systems.

[0136] In some embodiments, the present method of use includes clinically achieving a total ablation procedure time of about 105.2 minutes or less by the ablation catheter system.

[0137] In some embodiments, the present method of use includes clinically reducing by about 62% the total ablation time by the ablation catheter system as compared to previous clinically approved ablation catheter systems.

[0138] In some embodiments, the present method of use includes clinically achieving a total ablation time of about 46 minutes or less by the ablation catheter system.

[0139] In some embodiments, the present method of use includes clinically reducing the total fluoroscopy time of the ablation catheter system by about 80% from a previously clinically approved ablation catheter system.

[0140] In some embodiments, the present method of use includes clinically reducing the total fluoroscopy time by the ablation catheter system to about 6.6 minutes or less.

[0141] In some embodiments, the present method of use includes clinically reducing the total RF application duration of the ablation catheter system by about 83% from a previously clinically approved ablation catheter system.

[0142] In some embodiments, the present method of use includes clinically reducing the total RF application duration by the ablation catheter system to about 8.1 minutes or less.

[0143] In some embodiments, the total treatment time and fluoroscopy time of the ablation catheter system included about 105 minutes and 6.6 minutes, respectively.

[0144] In some embodiments, the present method of use includes disposing an esophageal temperature monitoring device and using the temperature monitoring device to monitor the esophageal temperature.

[0145] In some embodiments, the present method of use includes confirming the ACT more than 350 seconds before inserting the ablation catheter system into the left atrium and maintaining it throughout the procedure.

[0146] In some embodiments, the present method of use includes generating an anatomical map of the left atrium before an ablation procedure in the LA.

[0147] In some embodiments, the present method of use includes using an ablation pre-flow delay of at least 2 seconds before RF application.

[0148] In some embodiments, the method of use includes RF ablation via application of up to 90 W of RF power for up to 4 seconds.

[0149] In some embodiments, the method of use includes moving an ablation catheter system from a first position of a treatment site to a second position of the treatment site.

[0150] In some embodiments, the step of moving the ablation catheter system includes moving the ablation catheter system approximately 4 millimeters when a clinically effective ablation has been achieved.

[0151] In some embodiments, the step of moving the ablation catheter system includes moving the ablation catheter system substantially when a clinically effective ablation has been achieved within 20 seconds as determined by reduction of the electrogram and / or decrease in impedance.

[0152] In some embodiments, the method of use includes performing ablation of the left atrium and real-time PV isolation using an ablation catheter system.

[0153] In some embodiments, the method of use includes confirming entry block at all target PVs with a diagnostic catheter.

[0154] In some embodiments, the method of use includes visualizing the treatment site and the ablation catheter system using fluoroscopy.

[0155] In some embodiments, the method of use is to minimize the risk of esophageal injury by using an esophageal temperature probe, where a temperature increase is detected within the esophagus and then the tissue at the treatment site is cooled to a predetermined temperature, and includes visualizing the esophagus under fluoroscopy.

[0156] In some embodiments, the method of use includes that the ablation duration did not exceed 30 seconds on the posterior wall at the treatment site.

[0157] In some embodiments, the method of use includes clinically reducing the PVI ablation time of the ablation catheter system between the first RF application and the last RF application to the PV before confirmation of isolation and achievement of circumferential ablation, as compared to a previously clinically approved ablation catheter system.

[0158] In some embodiments, the method of use includes clinically reducing the subject PVI ablation time of the ablation catheter system between the first RF application and the last RF application before all PVIs are completed, as compared to a previously clinically approved ablation catheter system.

[0159] In some embodiments, the method of use includes clinically reducing the total ablation time of the ablation catheter system between the first RF application and the last RF application before all PVIs are completed, as compared to a previously clinically approved ablation catheter system.

[0160] In some embodiments, the method of use includes that the total ablation time is determined by the total procedure time from the first femoral puncture to the removal of the last catheter.

[0161] In some embodiments, the method of use includes clinically improving the ablation parameters of the ablation catheter system during the ablation procedure, as compared to a previously clinically approved ablation catheter system, including temperature, impedance, power, contact force, and RF duration.

[0162] In some embodiments, the method of use includes clinically improving the atrial mapping time.

[0163] In some embodiments, the method of use includes clinically improving the LA catheter dwell time from LA insertion of the ablation catheter to ablation catheter removal from the LA.

[0164] In some embodiments, the method of use includes perfusing cardiac tissue via an ablation catheter system.

[0165] In some embodiments, the method of use includes minimizing acute or minimal subendocardial hemorrhage in the ventricles and mitral valve by using an ablation catheter system when abolishing or alleviating persistent atrial fibrillation.

[0166] In some embodiments, the method of use includes demonstrating that the safety and / or efficacy of an ablation catheter system for patients in a given patient population has been clinically improved, where the given patient population is divided into three different arrhythmia subgroups, namely ventricular tachycardia, complex atrial tachycardia or recurrent paroxysmal atrial fibrillation, and persistent atrial fibrillation.

[0167] In some embodiments, the method of use includes clinically improving the safety and efficacy of an ablation catheter system for at least one of the left atrium, right atrium, left ventricle, and right ventricle.

[0168] In some embodiments, a system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF) is disclosed. The system includes an elongated body and an electrode assembly coupled to the elongated body, the electrode assembly comprising a shell configured with an inner chamber and a wall defining a proximal portion and a distal portion, the wall of the distal portion having at least one opening, a micro - element extending through the inner chamber between the proximal portion and the distal portion and having a distal end received within at least one opening, the distal end having at least the same extent as the outer surface of the wall. The system is configured with an ablation mode that includes a power setting of about 90 W applied to tissue in about 4 - second pulses with an interruption period of about 4 seconds during application.

[0169] In some embodiments, this ablation mode causes a maximum tissue temperature of about 76°C.

[0170] In some embodiments, the system includes a perfusion pump configured to deliver the infusion of a therapeutic solution by and through the elongated body. The perfusion pump is configured to deliver about 2 milliliters per minute of the therapeutic solution when RF energy is not being delivered during RF ablation. The perfusion pump is configured to deliver about 8 milliliters per minute of the therapeutic solution when RF energy is not being delivered during RF ablation.

[0171] In some embodiments, a force - sensing system is included for detecting the contact force applied to the treatment site by the catheter system during use, and the contact force between the system and the target site ranges from about 5 to 30 grams.

[0172] In some embodiments, the system is configured to achieve a zero incidence rate of steam pop in both left - atrial ablation and right - atrial ablation using the ablation mode.

[0173] In some embodiments, the ablation mode increases the maximum tissue temperature by at least about 13% between a first ablation application and a second ablation application.

[0174] In some embodiments, the ablation mode further deepens the lesion by about 40% between a first ablation application and a second ablation application, and the ablation mode further includes a contact force ranging from about 10 to 30 grams between the ablation catheter system and the target site.

[0175] In some embodiments, the ablation mode further deepens the lesion by about 40% between a first ablation application and a second ablation application, and avoids the formation of carbides, clots, and steam pops.

[0176] In some embodiments, the ablation mode includes a "kissing" ablation approach for each point that produces a continuous and transmural linear lesion line in the atrial wall with minimal overlap of the lesions.

[0177] In some embodiments, the ablation mode includes temperature control and a perfusion link.

[0178] In some embodiments, the electrode assembly comprises one or more ring electrodes and microelectrodes, and the catheter system is configured to clinically improve the pacing from the one or more ring electrodes and microelectrodes during the idle state and during high-frequency ablation.

[0179] In some embodiments, the system is configured to achieve an RF ablation time that is at least about 80% lower compared to the ablation time of a previously clinically approved catheter system for treating PAF.

[0180] In some embodiments, the distal end of the microelement includes an exposed portion outside the wall of the shell, and the microelement is configured for temperature sensing.

[0181] In some embodiments, the micro-elements further include a first plurality of first micro-elements configured for impedance sensing and a second plurality of second micro-elements configured for temperature sensing. The distal ends of the first micro-elements are arranged in a radial pattern along the outer periphery of the distal portion of the shell about the longitudinal axis of the electrode assembly.

[0182] In some embodiments, a method or use is disclosed that includes selectively positioning an ablation catheter system at a treatment site and ablating tissue at the treatment site with an ablation catheter system using a power setting of about 90 W applied to the tissue in about 4-second pulses with an interruption period of about 4 seconds between applications, and achieving a maximum tissue temperature of about 76° C. at the treatment site during the ablation procedure by the ablation catheter system.

[0183] In some embodiments, the step of ablating tissue includes increasing the maximum tissue temperature by at least about 13% between a first ablation application and a second ablation application.

[0184] In some embodiments, the step of ablating tissue includes a "kiss" ablation approach for each point that creates a continuous and transmural linear lesion line in the atrial wall with minimal overlap of the lesions.

[0185] In some embodiments, the step of ablating tissue includes achieving a lesion depth that is further about 40% deeper between a first ablation application and a second ablation application, and the method or use further includes applying a contact force ranging from about 5 to 30 grams to the treatment site by the distal end of the ablation catheter system.

[0186] In some embodiments, the ablation catheter system includes an elongated body, an electrode assembly comprising a shell configured with an inner chamber and a wall, and a microelement extending through the inner chamber between a proximal portion and a distal portion, the distal end of the microelement being received within at least one opening, the distal end having at least the same extent as the outer surface of the wall.

[0187] In some embodiments, the size of a given patient population is at least about 50 patients.

[0188] In some embodiments, the method or use includes delivering a continuous infusion of a therapeutic solution at about 8 milliliters per minute by and through the elongated body when RF energy is not being delivered during RF ablation.

[0189] In some embodiments, the method or use includes moving the ablation catheter system about 4 millimeters when a clinically effective ablation is achieved within 20 seconds as determined by a reduction in the electrogram and / or a decrease in impedance.

[0190] Disclosed is a method or use including delivering an ablation catheter system to a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor proximate to the other, ablating the cardiac tissue with the ablation catheter system at a power setting including a given perfusion flow rate and about 90 W, and achieving an incidence of steam pop of about zero and complete pulmonary vein isolation in both left atrial ablation and right atrial ablation for all patients in a given patient population suffering from PAF with the ablation catheter system.

[0191] In some embodiments, the ablation catheter system comprises an electrode assembly having an elongated body and a shell configured with an inner chamber and a wall, and a microelement extending through the inner chamber between a proximal portion and a distal portion, the distal end of which is received within at least one opening and has at least the same spread as the outer surface of the wall.

[0192] In some embodiments, the step of achieving complete pulmonary vein isolation further includes applying an average force of about 7.5 grams to cardiac tissue by the ablation catheter system during use and achieving a target temperature of about 50°C and an ablation duration of about 4 seconds.

[0193] In some embodiments, the step of achieving complete pulmonary vein isolation further includes applying an average force of about 9 grams to cardiac tissue by the ablation catheter system during use and achieving a target temperature of about 55°C and an ablation duration of about 4 seconds.

[0194] In some embodiments, the step of achieving complete pulmonary vein isolation further includes applying an average force of about 17.7 grams to cardiac tissue by the ablation catheter system during use and achieving a target temperature of about 1360°C and an ablation duration of about 4 seconds.

[0195] In some embodiments, the step of achieving complete pulmonary vein isolation further includes applying an average force of about 13.6 grams to cardiac tissue by the ablation catheter system during use and achieving a target temperature of about 1360°C and an ablation duration of about 2 seconds.

[0196] In some embodiments, the method or method of use includes delivering a treatment fluid having a predetermined perfusion flow rate of about 380 mL or less to a treatment site by the ablation catheter system during an ablation procedure.

[0197] In some embodiments, the step of achieving complete pulmonary vein isolation includes a total ablation treatment time of about 105 minutes or less.

[0198] In some embodiments, the step of achieving complete pulmonary vein isolation includes a total ablation treatment time of about 46 minutes or less.

[0199] In some embodiments, the step of achieving complete pulmonary vein isolation includes a total fluoroscopy time of about 6.5 minutes or less.

[0200] In some embodiments, the step of achieving complete pulmonary vein isolation includes a total RF application duration of about 8 minutes or less.

[0201] In some embodiments, the step of achieving complete pulmonary vein isolation includes a total RF application duration of 30 seconds on the posterior wall of the treatment site.

[0202] In some embodiments, the step of ablating cardiac tissue includes a "kiss" ablation approach for each point that produces a continuous and transmural linear lesion line on the atrial wall while minimizing lesion overlap.

[0203] For the achievement of the above object and related objects, specific exemplary aspects will be described herein in connection with the following description and the accompanying drawings. However, these aspects merely illustrate some of the various ways in which the principles of the claimed subject matter can be used, and the claimed subject matter is intended to encompass all such aspects and their equivalents. Other advantages and novel features will become apparent from the following detailed description when considered in conjunction with the drawings.

Brief Description of the Drawings

[0204] The above and further aspects of the present invention will be further considered with reference to the following description in conjunction with the accompanying drawings, in which like numbers in the various drawings indicate like structural elements and features. The drawings are not necessarily to scale, and instead, emphasis is placed on illustrating the principles of the present invention. The figures depict one or more implementations of the devices of the present invention by way of example and not limitation.

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Best Mode for Carrying Out the Invention

[0205] Representative embodiments of the disclosed technology are detailed herein, but it should be understood that other embodiments are contemplated. Thus, the following description is not intended to limit the scope of the technology disclosed to the details of the structure and arrangement of the components described in the following description or shown in the drawings. The disclosed technology is capable of other embodiments and of being practiced or carried out in various ways.

[0206] It should also be noted that in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. "Comprising," "containing," or "including" means that at least the compound, element, particle, or method step recited is present in the composition or article or method, but does not exclude the presence of other compounds, materials, particles, method steps, even if these other compounds, materials, particles, method steps have the same function as those recited.

[0207] As used herein, the term "about" or "approximately" with respect to any numerical value or range of numerical values indicates a preferred dimensional tolerance that allows a part of a component or a set of components to function in accordance with the intended purpose described herein. More specifically, "about" or "approximately" can refer to a range of values of ±10% of the recited value. For example, "about 90%" can refer to a range of values from 81% to 99%. Further, as used herein, the terms "patient," "host," "user," and "subject" refer to any human or animal subject and are not intended to limit the use of the system or method to use in humans, although the use of the present invention in human patients represents a preferred embodiment.

[0208] When describing exemplary embodiments, terms are used to make the discussion easier to understand. Each term is intended to have its broadest meaning as understood by those skilled in the art and is intended to include all technical equivalents that act in a similar manner to achieve a similar purpose. It should also be understood that a reference to one or more steps of a method does not exclude the presence of additional method steps or method steps intervening between those expressly identified. Each step of a method can be performed in an order different from the order described herein without departing from the scope of the disclosed technology. Similarly, a reference to one or more components in a device or system should be understood not to exclude the presence of additional components or components intervening between those expressly identified.

[0209] The vasculature of a "subject" or "patient" as described herein may be that of a human or any animal. It should be understood that the animal can be of any of a variety of applicable types, including but not limited to mammals, veterinary animals, domestic animals, or pet animals. By way of example, the animal can be an experimental animal (e.g., rat, dog, pig, monkey, etc.) specifically selected to have certain properties similar to those of a human. It should be understood that the subject can be, for example, any applicable human patient.

[0210] As used herein, an "operator" can include a physician, surgeon, or any other individual or delivery instrument involved in the delivery of an RF balloon catheter for the treatment of atrial fibrillation in a patient.

[0211] The term "safety" as used herein with respect to a device, associated delivery system, or method of treatment used for ablation of cardiac tissue refers to a relatively low severity of adverse events, including adverse bleeding events, infusion, or allergic reactions. An adverse bleeding event may be a primary safety endpoint and may include, for example, major bleeding, minor bleeding, and individual elements of a composite endpoint of any bleeding event.

[0212] As used herein, unless otherwise indicated, the term "clinically effective" (used alone or to modify the term "effective") is proven by clinical trials and may mean that the clinical trials meet the approval criteria of the US Food and Drug Administration, the EMEA, or the corresponding national regulatory agency. For example, the clinical trials may be appropriately sized randomized double-blind controlled trials used to clinically demonstrate the effectiveness of the cardiac ablation devices and related systems of the present disclosure. Most preferably, for example, it is most preferred to clinically demonstrate the effectiveness of the device for all target pulmonary veins in order to achieve clinically effective results in patients and / or to achieve pulmonary vein isolation in these affected veins.

[0213] In a preferred embodiment, the solution of the present disclosure is not a method for treating the human or animal body by surgery or therapy, nor a diagnostic method implemented on the human or animal body. For example, if the solution includes clinically improving at least one clinical attribute during use, the clinical attribute may not be related to a method for treating the human or animal body by surgery or therapy, or a diagnostic method implemented on the human or animal body.

[0214] The term "computed tomography" or "CT" as used herein means one or more scans that use a computer-processed combination of many X-ray measurements obtained from different angles to create a cross-sectional (tomographic) image (virtual "slice") of a specific area of the object being scanned, enabling the user to view the inside of the object without cutting. Such CT scans of the present disclosure can refer to X-ray CT, as well as many other types of CT such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT).

[0215] The present disclosure relates to a system and catheter for cardiac catheterization, the catheter having a sensing assembly that provides signals representative of both the position of the catheter and the pressure applied to the distal portion of the catheter when it engages tissue. Compared to conventional position sensing assemblies and pressure sensing assemblies, the sensing assembly of the catheter advantageously has a continuously wired sensing structure configured to reduce the number and / or the length of the leads with respect to a simplified catheter structure that minimizes the risk of lead damage and breakage. FIG. 1 is a schematic depiction of a conventional system 20 for cardiac catheterization known in the art. The system 20 can include an invasive probe in the form of a catheter 28 and a control console 34. The signal processor 36 of the console 34 processes signals from the sensors of the catheter 28 to determine the position coordinates of the distal portion 13, typically including both position coordinates and orientation coordinates. The test catheter 28 and corresponding features of the present disclosure may be understood to include the features more specifically described in Appendix 1, which includes U.S. Pat. Nos. 8,357,152; 8,437,832; 8,535,308; 8,706,193; 8,784,413; 8,818,485; 8,900,228; 9,737,353; 9,445,725; 9,980,652; 10,213,856; 10,517,667; 10,405,920; 10,292,763; 10,441,354; 10,307,206; 10,201,385; and U.S. Patent Application Nos. 14 / 289,802; 15 / 793,433; 15 / 295,296; and 16 / 272,098, each of which is incorporated herein by reference as if set forth in full in its entirety.In connection therewith, similar methods of position detection are described in U.S. Pat. Nos. 5,391,199, 6,690,963, 6,484,118, 6,239,724, 6,618,612, and 6,332,089, International Publication No. 96 / 05768, and U.S. Patent Application Publication Nos. 2002 / 0065455(A1), 2003 / 0120150, and 2004 / 0068178, the entire disclosures of which are hereby incorporated by reference, and in Appendix 1. FIG. 2 shows an overall view of the catheter of the present disclosure used to perform PVI.

[0216] It is important to note that there is published data on ablation at powers higher than standard power settings, usually 45W - 50W, for currently available ablation catheters. However, most of these retrospective studies were performed at a few sites with limited analysis of safety endpoints, and real-time tissue temperature monitoring was not possible with these catheters. On the other hand, another temperature-sensing irrigation catheter with a diamond-impregnated tip has been shown to significantly reduce treatment time. See Iwasawa J, Koruth JS, Petru J, et al., "Temperature-controlled radiofrequency ablation for pulmonary vein isolation in patients with atrial fibrillation," J Am Coll Cardiol 2017;70:542 - 53. However, this catheter is limited to 50W and thus cannot deliver a 4-second test ablation mode lesion, and when the lesions were averaged, they were 18.8 ± 1.9 seconds each with this catheter.

[0217] It is important to note that the test ablation (90W, 4s) described in the present disclosure differs from all previous tests which had a limit of 50W. The test ablation mode referred to in the present disclosure is understood to be 90W at a flow rate of 8 milliliters per minute and may also be referred to as QMODE+. The ability of the new test ablation mode to adjust power based on temperature reduces the potential for overheating of the electrodes and tissue, which in turn can help avoid char formation and steam pops. The safety profile observed with catheter 28 and the corresponding test ablation mode is promising, with a low incidence of PAE and no unexpected adverse device effects. Furthermore, the ability to emphasize only local potentials and not distant potentials makes the microelectrode useful for avoiding high-frequency delivery over scar tissue. The safety of the test ablation will be further evaluated in larger clinical trials. One of the limitations of point-by-point catheter ablation is the longer treatment time associated with forming individual lesions, which has promoted the adoption of balloon-based catheters for PVI. Still, current balloon technology is mostly limited to PV ablation. Current research has demonstrated a reduction in treatment time with test ablation that is shorter than that typically observed with currently commercially available CF and non-CF catheters.

[0218] As shown in FIG. 3A, the catheter 28 includes an elongate catheter body 11, a deflectable intermediate portion 12, a distal portion 13 carrying at least a tip electrode 15 at its distal tip 30, and a control handle 16. The catheter 28 may be an operable multi-electrode lumen catheter having a deflectable tip designed to facilitate electrophysiological mapping of the heart and to transmit radiofrequency (RF) current to the catheter tip electrode for ablation purposes. An operator 26, such as a cardiologist, may insert the catheter 28 through the patient 24's vasculature such that the distal portion 13 of the catheter enters the lumen of the patient's heart 22. The operator advances the catheter such that the distal tip 30 of the catheter engages the endocardial tissue 70 at a desired location or locations. The catheter 28 is connected to a console 34 by a suitable connector at its proximal end. The console may include an RF generator, which supplies high-frequency electrical energy through the catheter to ablate tissue within the heart at the location engaged by the distal portion 13. For ablation, the catheter 28 may be used in conjunction with a dispersive pad (e.g., different electrodes). In this regard, the catheter 28 may include a shaft measuring 7.5F using an 8F ring electrode.

[0219] Catheter 28 may also have a force sensing system that provides real-time measurement of the contact force between the catheter tip and the heart wall. To determine appropriate test ablation mode settings that can be proven to be safe and impart a uniform non-penetrating lesion near the PV periphery, a series of in vivo and in vitro experiments including a thigh muscle preparation model, as well as in vivo beating heart experiments, were conducted in conjunction with the tests of the present disclosure. Its main purpose was to identify and evaluate the optimal ablation settings that enable the maximum power output with the shortest possible duration without carbide or steam pop formation. A range of powers (e.g., 50 - 100 W) and durations (3 - 15 seconds) were studied and analyzed, and according to what the data from these evaluations suggest, by using higher power to promote resistive heating while shortening the duration to limit the effect of conductive heating through adjacent tissues, an optimal balance of efficiency, effectiveness, and safety is achieved. The conclusion from these tests is realized as a test ablation mode using ablation parameters of 90 W (perfusion setting of 8 milliliters per minute) for 4 seconds.

[0220] As shown in FIG. 3B, the distal tip portion 13 may include an electrode assembly 19 and at least one microelement 20 having a non-invasive distal end adapted for direct contact with the target tissue 22. The catheter body 12 may have a longitudinal axis and an intermediate portion 14 on the distal side of the catheter body 12 that can be deflected axially outward in one or two directions from the catheter body 12. There is an electrode assembly 19 having at least one microelement on the distal side of the intermediate portion 14. On the proximal side of the catheter body, there is a control handle 16 that enables the operator to manipulate the catheter, including deflection of the intermediate portion 14.

[0221] The shaft is capable of providing relatively high torque, and the distal tip portion 13 is relatively deflectable while accommodating an electrode assembly 19 having an array of electrodes including a 3.5 mm tip dome with three microelectrodes. All of these electrodes can be used for recording and stimulation purposes. A rocker lever can be used to deflect the tip. The high torque shaft also rotates the plane of the curved tip to facilitate accurate positioning of the catheter tip at the desired site. Three curved configurations designated "D", "F", and "J" are available. The electrode assembly 19 serves to deliver RF energy from an RF generator to the desired ablation site. The electrode assembly 19 and the ring electrode can be made of a noble metal. In some embodiments, the catheter 28 can also include six thermocouple temperature sensors embedded in the 3.5 mm tip electrode.

[0222] RF generator software can be configured for cardiac ablation by generating RF energy for delivery to a site within the heart via the catheter 28. The RF generator can include functions for controlling ablation parameters at the ablation electrodes of the catheter. Ablation parameters such as power, impedance, ablation duration, and temperature can be recorded and exported to a USB device at the end of the procedure. The RF generator can include a console that houses the hardware for providing RF energy delivery. A local monitor can be included along with a user interface. The monitor can include control instructions for the generator and can instruct the console as to which functions to perform. This can also communicate with a workstation. A foot pedal for the user to start and stop ablation can be included.

[0223] At the proximal end of the catheter 28, a saline input port having a standard luer fitting may terminate from the open lumen. This saline port serves to allow the injection of saline for perfusion of the electrode assembly 19. During ablation, heparinized saline may be passed through the internal lumen of the catheter 28 and also through the electrode assembly 19 to perfuse and cool the ablation site as well as the electrode tip. In certain embodiments, a perfusion pump may be used to control the perfusion of saline.

[0224] Referring now to FIG. 4A, which is a cross-sectional view of the distal tip portion 13 of the catheter 28, broken away, according to an embodiment of the present invention. The perfusion assembly 51 mates with the segment 81 of the catheter 28 and one or more electrodes 47 of the assembly 19. The assembly 51 includes an axial lumen 83 that carries the perfusion fluid distally toward the blocked termination end 85. This blocked termination end prevents the perfusion fluid from continuing to advance forward. The flow of the perfusion fluid is indicated by arrow 87. At the termination end 85, a plurality of passages 89 branch out axially transverse to the axial lumen 83 at an angle of 90° and direct the flow outwardly, as indicated by arrow 91. The perfusion fluid enters a lumen 49 that traverses the axis of the catheter 28 and generally heads toward a lateral passage (e.g., passage 61) within the electrode 47.

[0225] If the path of perfusion exits from the lumen 83 aligned with the axis of symmetry 53, the perfusion flow through the passage 61 would undesirably reverse direction. That is, this flow would need to be redirected, and more than 90° of redirection would be required to enter a proximally inclined passage (e.g., passage 61). The advantage of the arrangement of FIG. 4A is that the perfusion flow is more evenly distributed to all the holes of one or more electrodes 47 compared to when the flow exits the assembly 51 forward.

[0226] To control the perfusion of saline, a perfusion pump may be used. The catheter 28 may interface with standard recording equipment and a compatible RF generator via an attached extension cable having appropriate connectors. The catheter 28 may include a positioning sensor embedded in the distal tip portion 13 that transmits position and contact force information to the navigation system. For the purpose of identifying a reference position, an appropriate reference device may be required.

[0227] Referring to FIG. 4B, there is a schematic cross-sectional view of the distal segment of the ablation catheter of FIG. 4A, shown as terminating at the distal tip portion 13, which is formed from a biocompatible conductor such as platinum, palladium, gold, iridium, or an alloy of the foregoing, and has a symmetry axis 70. The cross-section of the distal end shown in FIG. 4B is taken in a plane containing the axis 70. The outer surface of the distal tip portion 13 is divided into three regions: a cylindrical region 78 at the proximal end of the tip, a planar region 82 at the distal end of the tip, and a curved annular region 86 joining the cylindrical region to the planar region.

[0228] In the illustrated embodiment, the distal tip portion 13 is penetrated by a perfusion passage such that the outer surface is perforated by a perfusion opening that terminates the passage. The perfusion fluid may be directed into the perfusion passage via an internal manifold 94 formed at the distal tip. The perfusion fluid for the manifold is provided by a dedicated conduit (not shown) within the lumen.

[0229] At least one cavity is formed within the cylindrical region 78. At least one cavity is formed within the curved annular region 86 of the outer surface. The embodiments described herein include three cavities symmetrically distributed with respect to the axis 70, and the three cavities of the curved annular region 86 are also symmetrically distributed with respect to its axis. Each cavity is configured to receive and mate with each respective microelectrode 120 of the tip electrode 15 described above. Each cavity of the curved annular region 86 is configured to receive and mate with each respective microelectrode 140. The microelectrode 120 is configured to be inserted into each respective cavity within the cylindrical region 78. The microelectrode 140 is configured to be inserted into each respective cavity of the curved annular region 86.

[0230] FIG. 5A shows a graph of power delivery over time by a generator RF at 35 W for a test of the present disclosure with a maximum duration set to 30 seconds. FIG. 5B shows a graph of power delivery over time by a generator RF at 50 W for a test of the present disclosure with a maximum duration set to 30 seconds.

[0231] FIG. 6A shows a graph of power delivery over time by a generator RF at 90 W for a test of the present disclosure with a maximum duration set to 4 seconds. FIG. 6B shows a graph of power delivery over time by a generator RF at 90 W for a test of the present disclosure with a maximum duration set to 4 seconds. The approach shown in FIGS. 6A - 6B is to titrate the power. In this setting, power delivery is at a constant perfusion flow rate of 8 milliliters per minute without modulation, considering the short duration.

[0232] FIG. 7 is a graph showing the biophysical parameters of an exemplary ablation lesion caused by the catheter 28 of the present disclosure. This includes a 2 - second pre - cooling stage followed by a 4 - second ablation lesion. Note the power modulation that is particularly prominent in the last 1.5 seconds of energy delivery to maintain a target temperature of 60°C.

[0233] Figure 8 presents the results of a meta-analysis of the estimated mean safety composite endpoint for a conventional device for PAF. Data from recent clinical trials on devices similar to catheter 28 in the current study were reviewed as a first step to derive performance goals for safety endpoints. A meta-analysis approach was taken to estimate the mean composite endpoint rate. Based on the plot, the upper limit of the 95% confidence interval was estimated to be equal to 9%. The proposed performance goal of 14% reflects an approximate 50% increase in risk from the upper limit of the 95% CI.

[0234] Furthermore, previous studies have reported a low incidence of major complications (0.8%), and at major centers around the world, the incidence associated with catheter ablation has been reported to be less than 5%. The most common complications associated with catheter ablation for AF included cardiac tamponade, which was reported to be approximately 0.2 - 5% mainly in catheter ablation of atrial fibrillation (AF) including the main PVI procedure.

[0235] The general incidence of pericardial fluid retention during AF ablation is approximately 1.2% - 1.3%. Cardiac perforation can result from catheter manipulation or application of high-frequency current. The reported risk of cardiac perforation is in the range of <1% - 2.4%. However, the risk of perforation has been decreasing with the advancement of catheter technology. This potentially life-threatening injury can cause cardiac tamponade and may also require percutaneous pericardial drainage or surgical repair. Marked hemodynamic deterioration can lead to neurological injury or death. An increased risk of cardiac perforation can be associated with the use of saline-irrigated electrode catheters, which is due to the fact that such catheters can create larger and deeper RF lesions. This risk is greatest in thin-walled chambers (i.e., RA, LA, appendages, or RV).

[0236] Pulmonary vein stenosis (PVS) is a well-known complication of radiofrequency catheter ablation for atrial fibrillation. The incidence of severe PVS (>70% diameter reduction) was found to be <1% in a recent study of 976 subjects. In a large systematic review of complications of radiofrequency catheter ablation, an incidence of only 0.5% was reported.

[0237] Furthermore, because the left atrium is anatomically close to the esophagus, catheter ablation on the LA posterior wall can thermally damage the esophagus and ultimately cause esophageal ulcers with a prevalence of 5%, although this rarely progresses to atrial-esophageal fistula (AEF) with devastating consequences. Endoscopic esophageal injury has a prevalence of 2.2 - 21%. Esophageal perforation is a serious complication of atrial fibrillation ablation that occurs in 0.02 - 11% of atrial fibrillation ablation procedures. Delayed diagnosis is associated with an increased incidence and mortality of atrial-esophageal fistula (AEF). The complication rate of esophageal injury varies widely depending on the location of the lesion and the type of lesion found (erythema, necrotic ulcer, perforation, or fistula formation). The incidence of AEF after ablation of AF is assumed to be approximately 0.1% of procedures. Studies using lumen temperature monitoring to identify potentially dangerous heating of the esophagus during ablation have not demonstrated a reduction in the incidence.

[0238] Currently, when isolation of the right PV cannot be obtained during pulmonary vein antrum isolation and RF ablation is performed inside the right PV at the thoracic apex, phrenic nerve paralysis is reported to be <0.5% and permanent paralysis is 0% - 0.4%. In a study published in 2018, a very low rate of PNP of 0.04% was reported among 2,750 procedures. Prior to ablation in the region of the RSPV, researchers are encouraged to implement preventive measures such as assessment of proximity to the phrenic nerve and pacing maneuvers.

[0239] Death is also a rare complication associated with CA technology. The overall incidence of death has been reported to be <0.1% to 0.4%. A worldwide survey published in 2010 showed an overall mortality rate of 0.1%. Another report from an international survey of AF ablation in 162 centers provided details of 32 deaths (0.1%) that occurred during or after AF ablation procedures in 32,569 patients. Among the most frequent causes of death were cardiac tamponade (25% of deaths), stroke (16%), atrio-esophageal fistula (16%), and massive pneumonia (6%).

[0240] High-frequency current can cause coronary artery occlusion either by direct thermal injury, contraction, or thrombosis. Acute coronary artery occlusion is a very rare but potentially life-threatening complication of RFCA. Experience at many centers suggests that the risk of coronary artery occlusion is less than 0.5%. Coronary artery occlusion can result in myocardial infarction (MI), angina, or death. Coronary artery occlusion can be treated by restoring coronary blood flow through pharmacological intervention, catheter, and / or surgical intervention as medically indicated.

[0241] Thrombus formation during the procedure can also be serious and pose a life-threatening risk to the patient. Thrombi can form on the ablation electrode during the application of high-frequency current, regardless of the presence or absence of impedance changes. Thrombi can be dislodged and embolize, causing ischemic stroke, MI, or other occlusive injuries. Although some observational studies have shown that the rate of stroke after catheter ablation is relatively low, it remains unclear whether catheter ablation can reduce the thromboembolic risk.

[0242] The average incidence of thromboembolism associated with AF ablation was approximately 1% - 2%. More recently, the incidence of thromboembolism has been reported to be up to 5% in patients undergoing AF ablation, despite perioperative anticoagulation. The onset of ischemic stroke typically occurs within 24 hours of the AF ablation procedure, and the higher-risk period extends up to the first two weeks after ablation.

[0243] Pulmonary hemorrhage is a rare but serious complication of PVI. Delayed hemoptysis and pulmonary hypertension may occur following pulmonary vein stenosis (PVS) after ablation. Acute pulmonary hemorrhage has also been reported. Mechanical trauma due to catheter manipulation is a possible mechanism of pulmonary hemorrhage. Damage to the heart valves can result from catheter manipulation or application of high-frequency current (risk < 1%). This can cause valvular insufficiency and may, in some cases, require valve replacement surgery.

[0244] Figure 9A is an exemplary temperature distribution display associated with catheter 28 of the tests in the present disclosure. Figure 9B is an exemplary "bull's eye" display associated with each thermocouple reading of catheter 28 of the tests in the present disclosure. The "bull's eye" display provides temperature information to the physician. Any numerical value of temperature from the RF generator can be displayed on the "bull's eye" determined by the preference of the physician to display or not display. The bull's eye graphic provides readings of the relative interface temperature between the tip and the tissue obtained from six thermocouples. This graphic provides the physician with an indication of which part of catheter tip 13 is in contact with tissue 22.

[0245] In addition, the graphic can also provide the physician with an indicator of the stability between the tip and the tissue. For example, if the catheter tip 13 slips, the temperature obtained from the thermocouple changes, which is visually displayed not only on the "bull's eye", but also on the graphic of the tip 13 of the catheter 28. The colors in these displays can change as the temperature of the thermocouple changes. The colors of the graphic in FIG. 9B are depicted here as black and white, but can range from dark blue (lowest temperature) to dark red (highest temperature), and the circular presentation enables the physician to visualize the relative temperatures of the distal and proximal thermocouples within the tip (viewed from the center outwards). The outer halo presents the orientation of the catheter tip in three-dimensional space.

[0246] FIG. 10 is a temperature profile that monitors the maximum temperature measured and used to verify the appropriate response of the temperature profile of the catheter tip 13 during an RF ablation session. The temperature feedback display during ablation is shown in FIG. 10, where six small circles represent six thermocouples (e.g., three distal and three proximal). The inner circle represents the electrode assembly 19, and the outer ring represents the sides of the tip electrodes. Any change in the desired orientation of the tip 13 (e.g., from a perpendicular orientation to the tissue 22) can result in a temperature increase in the corresponding portion of the electrode assembly 19, as indicated by the darker color in the lower quadrant.

[0247] Summary of the investigation The present disclosure will be more clearly understood in the corresponding investigations described in more detail below with respect to the mapping and / or treatment of PAF. FIG. 11 presents an overview of the test protocol of the subject matter of the present disclosure, and this test protocol is attached to this specification in Appendix 2, and all of its contents are incorporated herein by reference as if they were described verbatim herein. All patients considered for RF ablation treatment for drug-refractory recurrent symptomatic PAF were evaluated for test eligibility for each protocol inclusion and exclusion criteria in a test by a researcher or a designated investigator of the research team. The pre-treatment evaluation was performed within 30 days before the index AF ablation treatment, unless otherwise specified.

[0248] The primary objective of this trial was to demonstrate the clinical safety and efficacy when catheter 28 is used with the RF generator of the present disclosure in the treatment of drug-refractory symptomatic paroxysmal atrial fibrillation (PAF) during standard electrophysiological mapping and RF ablation treatment. To succeed in the trial, both endpoints had to be statistically significant with respect to their respective performance goals. The primary safety endpoint was the proportion of subjects having any major adverse event (PAE) occurring within 7 days from the ablation treatment. The PAE rate was compared with the primary target of 14%. The primary efficacy endpoint of this trial was the proportion of patients without confirmed atrial arrhythmia (atrial fibrillation (AF), atrial tachycardia (AT), or atrial flutter (AFL)) episodes at 12 months (i.e., during the 9 months after the blank period, i.e., from day 91 to day 365). Another objective of this trial was to demonstrate safety based on the proportion of subjects with early-onset (within 7 days from the ablation treatment) major adverse events.

[0249] The primary secondary objective of this trial was to evaluate the incidence of (serious) adverse events during the procedure and up to 3 months after the procedure in order to assess the emergency procedure success rate, defined by the percentage of subjects who received electrical isolation of the PV (entry block) at the end of the procedure and the percentage of subjects who received electrical isolation of the PV (entry block) using QMODE+ as the sole ablation strategy. Another secondary efficacy endpoint was the combination of the percentage of subjects who received electrical isolation of the PV (entry block) at all power settings and the percentage of subjects who received electrical isolation of the PV (entry block) after the first pass isolation, after completion of the waiting period and adenosine loading. Another secondary efficacy endpoint was the percentage of subjects and the percentage of PVs with touch-up (i.e., touch-up was used to exclude ablation of acute reconnection) among all target veins and touch-up sites. Another secondary efficacy endpoint was the anatomical location of acute PV reconnection after the first enclosure. Another objective of this trial was to compare the primary efficacy of catheter 28 with the established performance target of 50% as the minimum acceptable success rate for the paroxysmal AF population over 12 months.

[0250] The secondary safety endpoints of this trial included the incidence of device-unexpected adverse effects (UADE), the incidence within 7 days (early onset), >7 days to 30 days (perioperative), and >30 days (late onset) from the first ablation, and the incidence of hemorrhagic complications (ISTH definition) of a) severe bleeding, b) clinically relevant non-severe bleeding, and c) mild bleeding. Another objective of this trial was to evaluate the safety and performance of the electrode catheter 28 of the present disclosure using the test ablation mode compared to a conventional catheter using a power control mode using a well-established canine thigh muscle model.

[0251] Catheter 28 was not used in the test under the test ablation mode without perfusion flow and maintained this higher flow rate. When the researcher deems it impossible to complete PVI in QMODE+, a power control mode sometimes called QMODE herein was used for PVI. In addition, QMODE temperature control was used for all RF applications outside the PV orifice during the test ablation procedure. QMODE included either (a) 25 - 35 W at a flow rate of milliliters per minute or (b) 36 - 50 W at a flow rate of 15 milliliters per minute. QMODE is a relatively high flow rate that starts at a maximum of 2 seconds and a minimum of 2 seconds from the start of RF energy delivery and maintains this higher flow rate for up to 4 seconds after the end of energy application. In this test, QMODE+ was used as the primary mode for PVI. However, when the researcher deemed QMODE+ unable to achieve PVI, catheter 28 in QMODE was used to complete the procedure.

[0252] Catheter 28 was evaluated for clinical safety and performance according to the following objectives, namely, (1) the carbide / clot and steam pop rate of catheter 28 using its test ablation mode compared to a conventional catheter using a power control mode, (2) comparison of the lesion dimensions (maximum depth, maximum diameter, and surface diameter) between catheter 28 and a control catheter, and (3) collection of ablation parameters, namely, average output, maximum electrode temperature, temperature rise, initial impedance, impedance drop, to understand the similarities and differences in behavior when compared to a control catheter.

[0253] A further objective of this test was to evaluate the safety and performance of catheter 28 when simulating a clinical PVI procedure using a test ablation mode (e.g., nMARQ multi-channel RF generator). Also, the overall safety and functional performance of catheter 28 using that test ablation mode were compared to those of the Smart Touch SF control catheter (control catheter 1) used in a power control mode (i.e., Smart Ablate generator). Catheter 28 was evaluated as being able to (1) deliver RF energy to the target site, (2) demonstrate acute isolation of the pulmonary vein, (3) demonstrate clinically acceptable signal quality equivalent to the control, (4) pace from the ring and microelectrodes during the idle state and during ablation, (5) provide significantly better temperature feedback than the control catheter during ablation, and (6) function effectively when used with ancillary devices (e.g., RF generator, QDOT dongle, CoolFlow pump, and CARTO 3 mapping system, etc.).

[0254] A further objective of this test was to evaluate the safety and performance of catheter 28 in a test ablation mode (e.g., about 90 W / 4 s, etc., high power and short duration) using the RF generator of the present disclosure. The overall safety and performance of catheter 28 in the test ablation mode were compared to the safety and performance of control catheter 1 in two different settings (50 W / 10 s or 30 W / 30 s) using an RF generator (e.g., Smart Ablate RF generator), particularly when used with an in vivo canine thigh muscle model. Catheter 28 was evaluated for the test ablation mode with respect to safety and performance, for the following subjects, namely, (1) the safety (e.g., carbide / clot and steam pop rate) of catheter 28 using the test ablation mode compared to control catheter 1 using its power control mode, (2) comparison of the damage dimensions (maximum depth, maximum diameter, and surface diameter) between the test catheter and the control catheter, and (3) average power, maximum electrode temperature, temperature rise, initial impedance, and impedance decrease.

[0255] In the ablation procedure itself, the subject arrived at the electrophysiology laboratory for his / her ablation procedure and received preparation for the procedure according to the hospital's standard protocol (at the discretion of the principal investigator of the clinical trial). The ablation procedure utilized the ablation modes described herein (e.g., QMODE and QMODE+ temperature control mode) to treat subjects with PAF. The test ablation mode of QMODE+ for temperature control was mainly used for PVI. The power control mode of QMODE temperature control was mainly used for AF applications outside the PV ostium and for touch-up of PVI. Figure 12 shows a table summarizing the equipment used in this test.

[0256] Figure 13 shows a table summarizing the effects on AAD and primary efficacy classifications for the tests of the present disclosure. This test investigated class I drugs (e.g., flecainide, propafenone, disopyramide, etc.) and class III drugs (e.g., amiodarone, dronedarone, dofetilide, etc.). The table in Figure 13 shows the corresponding status of the primary efficacy endpoints based on AAD therapy conducted during the blank period and the post-blank period.

[0257] Figure 14 shows a table summarizing the ablation mode and flow rate settings during RF application. The rows with a power setting of 90W correspond to the test ablation mode. The temperature displayed on the RF generator during the test does not necessarily represent the tissue temperature or the electrode-tissue interface temperature. The perfusion pump associated with the catheter 28 being investigated was configured to deliver a continuous infusion of room temperature heparinized saline (1u heparin / 1 milliliter saline) at 2 milliliters per minute when RF energy was not being delivered. The perfusion was increased to a high flow rate starting 2 seconds before the bottom of the start of RF energy delivery. When using catheter 28 in QMODE and QMODE+ in the test, the recommended contact force range of action was 5 - 30g.

[0258] For this test in the test ablation mode, the AF ablation procedure followed the following sequence, namely, (1) diagnostic catheter placement, (2) electrophysiological testing (at the discretion of the researcher), (3) cardioversion in the case of the subject being in AF (at the discretion of the researcher), (4) CARTO® Respiratory Gating Mandatory (unless Jet Ventilation is used), (5) placement of an esophageal temperature monitoring device, (6) confirmation of ACT at ≥ 350 seconds before insertion of catheter 28 into the left atrium and maintenance throughout the procedure, (7) transseptal puncture, and (8) a left atrial anatomical map was recommended / required prior to the ablation procedure in the LA. The anatomical map did not require triggers outside the left atrium (e.g., SVC / CS, etc.). This sequence may include (9) introduction of catheter 28, the introduction of which may include the following steps, namely, tagging each QMODE+ ablation point after each application using the AUTOTAG function of Carto, ensuring catheter stability before starting RF application at a new location, having a flow delay of at least 2 seconds before ablation occur before RF application, ablating via RF power application of up to 90 W (QMODE+) for up to 4 seconds, moving the catheter to a new location (about 4 millimeters) if a clinically effective ablation is achieved, and QMODE+ being used for complete PV isolation. If the researcher considered QMODE+ unable to achieve PVI, catheter 28 in QMODE was used to complete the procedure. Step (9) may also include continuing RF application and movement of catheter 28 until circumferential PVI is completed.

[0259] When the temperature rose above the temperature cutoff (e.g., 65 °C), RF application was immediately stopped. The decision to interrupt RF power delivery at any point during ablation was guided by the judgment of the researcher and by monitoring ablation efficacy parameters including catheter movement, reduction of electrograms, and / or impedance changes. For ablation in the region of the right superior PV, preventive measures such as pacing maneuvers were used to evaluate proximity to the phrenic nerve.

[0260] This sequence may also include: (10) left atrial ablation and real-time PV isolation, (11) a 20-minute waiting period after ablation before pacing maneuvers and / or injection of cardiac therapeutic agents (e.g., adenosine, isoproterenol 2 - 20 micrograms / min) to induce AF / reconnection, (12) confirmation of entry block in all target PVs by Lasso® or PentaRay®, and (13) performance of a fluoroscopic evaluation of the diaphragm.

[0261] This was required to minimize the risk of esophageal injury in this study. This method used one of the following for localization: (1) use of an esophageal temperature probe, (2) visualization of the esophagus by CARTOSOUND® and / or ICE, or (3) visualization of the esophagus using barium swallow. In the case of an increase in esophageal temperature, the following occurred: (1) the tissue was cooled and additional damage was made at the same or nearby locations, (2) if isolation was not achieved, move away from that spot, ablate other areas first, and then return to that spot, (3) QMODE was used at the operator's normally selected posterior wall power and duration as needed, still very carefully monitored for temperature increase and not started until the esophageal temperature returned to baseline, and (4) if the above two steps did not achieve the task, ablate in an area near but slightly away from that area.

[0262] Figure 15 shows a table summarizing the necessary schedule for the treatment and evaluation of subjects in the present disclosure. In this table, the numbered annotations correspond as follows: (1) The initial ablation procedure should be performed within 30 days from consent. (2) Collected to confirm no change in the medical history since the last visit. (3) AEs collected after consent were signed to confirm no change in the medical history since the last visit. (4) If hospitalization resulted from the AE outcome, health economic data collection was required. (5) Quality of life tool (AFEQT) (6) Pregnancy test must be performed only on premenopausal women within 24 hours of the procedure. (7) Subjects should undergo imaging diagnosis for the presence of LA thrombus. (8) Imaging TTE to determine atrial size (if the subject has undergone an imaging diagnostic procedure for atrial size evaluation within the last 6 months, a pre-treatment imaging diagnostic evaluation is not required). (9) After the procedure, all subjects should undergo a TTE procedure to evaluate the pericardium for pericardial fluid retention and / or pericarditis. (10) Concurrent medications: only heart-related (antiarrhythmic drugs, anticoagulation regimen, etc.). (11) PV imaging (CT / MRA) of subjects with symptoms undergoes follow-up observation for 7 days in the 1 month after ablation. (12) Health economic data for hospitalization (UB04), ER visit, and outpatient visit if applicable. (13) TTM: All symptomatic cardiac episodes should be recorded and transmitted at the time the event occurs. (14) 12-month visit or the last visit completed. (15) In some cases, virtual visit or in-person visit. (16) Required only for in-person visit. (17) In the case of stroke, a modified Rankin score is assessed to evaluate the degree of disability of the subject suffering from the stroke. (18) A standardized neurological evaluation (including cranial nerves, motor and sensory functions, and gait evaluation) is performed. If this neurological evaluation reveals new abnormalities, the patient should also undergo a formal neurological diagnosis and examination using appropriate imaging diagnosis (i.e., DW-MRI) used to confirm the suspected diagnosis. (19) All subjects who undergo repeated ablation procedures with catheter 28 during the blanking period are either suggestive of PV stenosis or are in the middle of a CT / MRA PV analysis procedure.

[0263] In this trial, a "harmful event" was considered to be any adverse clinical sign, unintended disease or injury, or adverse clinical sign (including abnormal laboratory findings) that occurred during the clinical trial, regardless of whether it was related to the test device or ablation procedure. For the purposes of this trial, harmful events were considered to occur as follows: namely, the event was essentially vascular, cardiovascular, or neurological; the event was a serious harmful event; the causal relationship was related to catheter 28 and its ablation procedure; or the cause was essentially unknown.

[0264] In contrast, the following clinical events, namely, any medical condition present at the time of examination as long as the condition of the subject of the trial did not deteriorate at any time during the trial, asymptomatic minimal / trace pericardial fluid retention, recurrence of existing AF / AFL, and AF / AFL / recurrence requiring pharmacological cardioversion at any time during the entire trial period, excluding the new onset of left atrial fibrillation occurring after ablation, and repeat ablation for AF or existing AFL / AT were not considered harmful events of this clinical trial. However, any complications related to the repeated ablation procedure were considered AEs.

[0265] Figures 16, 17, 18, and 19 show a summary of the primary harmful events determined in the trial of the present disclosure. As shown in those figures, the primary AEs in this trial were one of the events listed in Figures 16 to 19. Those events occurred within 7 days from the AF ablation procedure using catheter 28 used with the RF generator described in this specification, with the exceptions of atrial-esophageal fistula and PV stenosis, which could also be considered primary harmful events if they occurred more than 7 days and within 90 days from the ablation procedure.

[0266] Serious adverse events (SAEs) in this trial were considered any event that met one or more of the following criteria: led to death, life-threatening illness or injury, or permanent impairment of body structure or function; led to a significant deterioration in the health of the subject; required hospitalization or prolongation of an existing hospitalization; or resulted in medical or surgical intervention to prevent permanent impairment of body structure or function; fetal distress, fetal death, or congenital anomaly or birth defect.

[0267] Figure 20 is a table summarizing the intensity or severity of the trials of the present disclosure, by which the intensity or severity of AEs is defined. Intermittent AEs are classified according to their maximum severity. Continuous AEs that change in severity are reported as new AEs.

[0268] In the power control mode, the workflow functions as follows. When the temperature rises rapidly, the RF application is immediately stopped. For atrial ablation, an RF power range of 15 to 50 watts (W) was used. At anatomical locations other than the LA posterior wall or CS, the maximum allowable power did not exceed 50 W, and the duration of ablation did not exceed continuous ablation of 60 seconds at a given location. Catheter 28 was moved or dragged to a new location when a clinically effective ablation was achieved (e.g., reduction of electrogram and / or impedance decrease).

[0269] During ablation of the posterior wall and coronary sinus, the following preventive measures were taken. When close to the LA posterior wall and esophagus, ablation was initiated using the standard workflow for the posterior wall. Catheter 28 was moved or dragged to a new location if clinically effective ablation was achieved within 20 seconds (e.g., decrease in electrogram and / or impedance drop). The maximum power used for ablation of the posterior wall and coronary sinus did not exceed 35 W, except when using the test ablation mode. The temperature change of the esophagus was monitored by the intracavitary esophageal probe or method used to move the esophagus. The duration of ablation did not exceed 30 seconds for the posterior wall.

[0270] Treatment data collection was performed using anonymized (or de-identified) generator files, anonymized (or de-identified) CARTO (registered trademark) data files, treatment worksheets, and subject medical files. Treatment data documents were stored for research analysis in the subject's CRF, anonymized (or de-identified) backup generator files, and backup CARTO (registered trademark) data files. Information collected during the treatment included, but was not limited to, RF application mode (QMODE+ / QMODE / others) for each lesion, number of RF applications using catheter 28 (total / QMODE+ / QMODE) and non-research catheters, duration of RF application using catheter 28 (total / QMODE+ / QMODE) and non-research catheters, PVI ablation time (time from the first RF application to the last RF application to the PV until isolation was confirmed and circumferential ablation was achieved), subject's PVI ablation time (time from the first RF application to the last RF application until all PVIs were completed), subject's total ablation time (time from the first RF application to the last RF application in the subject), ablation parameters for each RF application (position, temperature, impedance, power, contact force, RF duration, ablation index, lesion information on CARTO (registered trademark)), number of ablation occurrences on the generator regarding the first and last RF applications for each target (left PV target, right PV target, and targets outside the PV area), ablation parameters for touch-up application (position, RF application mode, amount of touch-up application, duration, and related generator file number), total treatment time (from the first femoral puncture to the last catheter removal), atrial mapping time, fluoroscopy time and dose, LA catheter dwell time (from LA insertion of the ablation catheter to LA removal of the ablation catheter), ECG data, total fluid delivered via the ablation catheter and venous line, fluid output and net fluid input, strategies used to minimize the risk of esophageal injury, and abnormal esophageal temperature rise.

[0271] Subjects in this trial were required to complete follow-up visits over 12 months (365 days) following the initial ablation procedure. The follow-up schedule was based on 30-day months. Follow-up visits were scheduled according to the following time frames, namely, 7 days (day 7, days 7 - 10), 1 month ± 7 days (1 month, days 23 - 37), 3 months ± 14 days (3 months, days 76 - 104), 6 months ± 30 days (6 months, days 150 - 210), and 12 months ± 30 days (12 months, days 335 - 395). The follow-up visit schedule was not reset if the subject underwent repeated AF ablation procedures.

[0272] Prior to discharge, a physical examination including a standardized neurological evaluation (including cranial nerves, motor and sensory functions, and gait evaluation) was performed before discharge. If the neurological evaluation showed new abnormal findings compared to those performed at baseline, formal neurological diagnosis and examinations using appropriate imaging (e.g., DW-MRI) were conducted to confirm a suspected diagnosis of stroke. The NIH Stroke Scale (NIHSS) was performed by a certified healthcare provider before discharge. Other pre-discharge events included detecting the occurrence of arrhythmias, electrocardiogram (12-Lead ECG), and transthoracic echocardiogram (TTE) for pericardial evaluation regarding possible pericardial fluid retention and / or pericarditis. If significant pericardial fluid retention was identified, the subject was followed until the symptoms resolved. Ablation procedures were recorded until the end of follow-up, including the type and name of medications, related instructions, start and end dates of prescriptions, etc., so cardiac-related concomitant medications (AAD, anticoagulation regimen, etc.) were prescribed.

[0273] Patient Selection The criteria regarding patient selection, methods, personnel, facilities, and training specified in this trial were aimed at minimizing the risks to subjects undergoing this procedure. Subjects were carefully pre-screened before enrollment to ensure compliance with the trial subject criteria and exclusion criteria.

[0274] The selection criteria for the investigation included the following.

[0275] · Symptomatic paroxysmal AF with AF episodes recorded on a single electrocardiogram · Physician's notes indicating recurrent self-terminating AF within 6 months prior to registration and within 7 days. Evidence may include electrocardiogram (ECG), transtelephonic monitoring (TTM), Holter monitor, or telemetry strip. · Failure of at least one antiarrhythmic drug (AAD) (class I or III), as demonstrated by recurrent symptomatic AF, contraindications, or intolerance to AAD. · 18 years of age or older. · Signed patient consent documentation (ICF). · Ability and willingness to comply with all pre, post, and follow-up examination requirements and visit requirements.

[0276] The exclusion criteria for the investigation included the following. · History of surgical or catheter ablation procedures for atrial fibrillation. · AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac causes. · Administration of amiodarone to the patient at any time within the past 3 months prior to registration. · Previously diagnosed with persistent or long-standing AF and / or continuous AF lasting more than 7 days · CABG surgery within the past 6 months (180 days). · Surgical / percutaneous procedures for valvular heart disease (i.e., ventriculotomy, atriotomy, valve repair or replacement, and presence of prosthetic valve). · Any carotid artery stenting or carotid endarterectomy within the past 6 months. · LA thrombus recorded on imaging (within 48 hours prior to the test ablation procedure). · Recorded LA size > 50 mm (parasternal long-axis view). · Recorded LVEF < 40%. · Contraindication to anticoagulant therapy (e.g., heparin) · History of blood coagulation or bleeding disorders · MI / PCI within the past 2 months (60 days). · Recorded thromboembolic events (including TIA) within the past 12 months (365 days) · Rheumatic heart disease · Uncontrolled heart failure or NYHA functional class III or IV · Severe mitral regurgitation (regurgitant volume of 60 mL / beat or more, regurgitation rate of 50% or more, and / or effective regurgitant orifice area of 0.40 cm 2 or more) · Scheduled heart transplantation or other heart surgery within the next 12 months (365 days) · Unstable angina · Active systemic infection or sepsis · Diagnosis of atrial myxoma or presence of an atrial septal baffle or patch · Presence of an implanted ICD / CRT-D · Severe pulmonary diseases causing chronic symptoms (e.g., restrictive lung disease, systolic or chronic obstructive pulmonary disease, etc.) or other pulmonary or respiratory diseases or dysfunctions · Severe gastroesophageal reflux disease (GERD; active ingredient requiring significant intervention not including OTC medications) · Major congenital anomalies or medical problems that, in the investigator's opinion, would make enrollment in this study impossible · Pregnant women (proven by pregnancy test in premenopausal women), lactating women, or women of childbearing age planning to become pregnant during the course of the study · Enrollment in an investigational study evaluating another device, biological product, or drug · Presence of an intramural thrombus, tumor, or other abnormality that would prevent vascular access or catheter manipulation · Presence of an inferior vena cava filter · Contraindications to the devices (TTE, CT, etc.) used in the study as indicated in their respective instructions for use · Estimated life expectancy of less than 12 months

[0277] Investigation results In this trial, catheter 28 was evaluated and compared to the achievement criteria of historical controls using 185 evaluable subjects. Figure 21 is a table summarizing the AE results evaluated in the trial of the present disclosure. Figure 22 is a graph summarizing the patient characteristics and medical history in the trial of the present disclosure. Figure 23 is a graph summarizing the acute pulmonary vein reconnection in the trial of the present disclosure. Figure 24 is a graph summarizing the major adverse events in the safety population of the trial of the present disclosure.

[0278] First and importantly, in preclinical trials, ablation with catheter 28 was shown to result in RF times that were less than 80% compared to conventional ablation. Accordingly, in the trial of the present disclosure, all 52 patients received ablation and completed follow-up. PVI was achieved in all patients using catheter 28 alone, with treatment times and fluoroscopy times of 105.2 ± 24.7 minutes and 6.6 ± 8.2 minutes, respectively. Most patients (n = 49; 94.2%) were in sinus rhythm at 3 months. Two PAEs were reported, one being a pseudoaneurysm and one being an asymptomatic thromboembolism. There were no deaths, strokes, atrial-esophageal fistulas, PV stenoses, or unexpected adverse device effects. Six patients had SCL confirmed and were all classified as asymptomatic without clinical or neurological deficits. Consistent with most of the PAF population, the registered patients were relatively young (62.0 ± 12.0 years), approximately two-thirds were male, the overall proportion of comorbidities was moderate (63.0% had hypertension, 18.5% had congestive heart failure), and the anteroposterior left atrial diameter was moderately enlarged (39.3 ± 5.2 mm). Of the 52 participants who received ablation, PVI was performed on all, and only 1 patient received additional ablation (left atrial roof, and the line between the left inferior PV and the right inferior PV). A second ablation for PAF was not required during the follow-up interval. The total number of high-frequency applications was 108.3 ± 42.5 at CF 16.9 ± 6.7 grams (minimum 8.1 grams and maximum 36 g) and power 85.4 ± 6.7 W.

[0279] Figure 25 is a graph summarizing the treatment parameters in the test of the present disclosure. As shown in the figure, the total treatment time understood as the time from the first puncture to the removal of the last catheter, including a 20-minute waiting time and an adenosine or isoproterenol load, was 105.2 ± 24.7 minutes (range 68.0 to 177.0 minutes). Of this total treatment time, the mapping time was 9.5 ± 5.3 minutes, the fluoroscopy time was 6.6 ± 8.24 minutes, the total PV ablation time was 44.3 ± 22.4 minutes, the total ablation time (from the time of the first high-frequency application to the time of the last high-frequency application) was 46.0 ± 21.3 minutes, and the left atrial residence time (time from catheter insertion into the left atrium to removal from the left atrium) was 81.7 ± 20.2 minutes. For the 50 patients in whom data were collected, the volume of fluid delivered by the ablation catheter was 382.4 ± 299.1 mL.

[0280] Figure 26 is a graph summarizing the treatment results in the test of the present disclosure. As shown in the figure, the treatment results of catheter 28 evaluated in this test are significantly improved compared to other previous multi-center tests. Important treatment parameters are shown for both this test and previous multi-center tests. The THERMOCOOL AF trial investigated a saline-irrigated radiofrequency ablation catheter, the SMART-AF trial investigated a saline-irrigated force-sensing ablation catheter, and the SMART-SF trial investigated a saline-irrigated enhanced force-sensing ablation catheter.

[0281] Figures 27A - 27B are tables summarizing the results of a comparative procedure between the catheter of the present disclosure and a previously clinically approved device. With respect to the fluid delivered by the ablation catheter during the procedure of this test, the catheter 28 of the present disclosure recorded a total average flow rate of 382.4 mL delivered, which is an improvement of approximately 57.4% (i.e., approximately 898.4 mL) over Smart Touch SF, an improvement of approximately 79.7% (i.e., approximately 1879.6 mL) over Smart Touch AF, and an improvement of approximately 57.4% (i.e., approximately 898.4 mL) over THERMOCOOL. With respect to the total procedure time by the ablation catheter during the procedure of this test, the catheter 28 of the present disclosure recorded an average total procedure time of approximately 105.2 minutes, which is an improvement of approximately 41.9% (i.e., approximately 181.1 minutes) over Smart Touch SF, an improvement of approximately 52.8% (i.e., approximately 222.7 minutes) over Smart Touch AF, and an improvement of approximately 49.9% (i.e., approximately 210.1 minutes) over THERMOCOOL.

[0282] Regarding the total ablation time by the ablation catheter during the treatment of this test, the catheter 28 of the present disclosure recorded an average total ablation time of about 46 minutes, which is an improvement of about 55.9% (i.e., about 104.3 minutes) compared to Smart Touch SF, an improvement of about 62.1% (i.e., about 121.5 minutes) compared to Smart Touch AF, and an improvement of about 58.3% (i.e., about 110.3 minutes) compared to THERMOCOOL. Regarding the total fluoroscopy time during the treatment of this test, the catheter 28 of the present disclosure recorded an average total fluoroscopy time of about 6.6 minutes, which is an improvement of about 64.5% (i.e., about 18.6 minutes) compared to Smart Touch SF, an improvement of about 84.1% (i.e., about 41.5 minutes) compared to Smart Touch AF, and an improvement of about 86.7% (i.e., about 49.7 minutes) compared to THERMOCOOL. Regarding the total RF ablation time during the treatment of this test, the catheter 28 of the present disclosure recorded an average total RF ablation time of about 8.1 minutes, which is an improvement of about 83.6% (i.e., about 49.5 minutes) compared to Smart Touch SF, an improvement of about 86.6% (i.e., about 60.6 minutes) compared to Smart Touch AF. The previously known figures for the total RF ablation time of THERMOCOOL were unknown. Compared with previous tests using CF and non-CF catheters, catheter 28 clearly showed significantly shorter total treatment time, total ablation time, total fluoroscopy time, and total high-frequency application time, as well as less perfusion fluid load.

[0283] Figure 28 is a table summarizing the results of ablation by setting at all locations of the test. Figure 29 is a table summarizing the results of ablation by setting at all locations of the test. Specifically, this table shows information regarding the first-pass isolation versus acute reconnection in the test ablation mode using catheter 28 during the treatment of this test.

[0284] The primary efficacy endpoint (PVI confirmed after adenosine or isoproterenol challenge) was achieved in all patients using catheter 28. In 78.8% (41 / 52) of cases, PVI was achieved using only the test ablation mode. PV reconnection after adenosine / isoproterenol was promoted with further damage in 26.9% of patients (14 / 52) and in 5.0% of veins (22 / 444), mostly progressing posteriorly. The initial lesion was created by a combination of test ablation and standard ablation in five veins and by test ablation in only 17 other veins showing acute reconnection. There were no applications made with the non-test catheter. At the 3-month follow-up visit, 49 patients (94.2%) were in sinus rhythm, two patients were in AF, and one was in atrial flutter.

[0285] Two PAEs (2 / 52, 3.8%) were reported, one was a femoral pseudoaneurysm (classified as SADE and treated successfully with thrombin injection), and the other was an asymptomatic thromboembolism (two new microemboli present on MRI at discharge and reconfirmed 1 and 5 months after the procedure). There were no deaths, strokes, atrial-esophageal fistulas, PV stenoses, or unexpected adverse device effects. An additional SADE (esophageal ulcerative bleeding) was observed by endoscopy on day 1 after the procedure and treated medically.

[0286] Among 51 patients who underwent MRI after ablation, SCL was found in 6 patients (6 / 51, 11.7%). Four of these patients received anticoagulation without interruption for at least 3 weeks before ablation, 1 patient received warfarin but it was interrupted the day before the procedure, and 1 patient did not use anticoagulation therapy. All lesions were classified as asymptomatic cerebral embolisms on the premise that there were no clinical or neurological deficits (evaluated by NIHSS, mRS, and MoCA). In 5 patients with 1 new microembolism, the lesions resolved within 1 month. The reported incidence of post-ablation cerebral lesions has varied widely in previous studies, but these lesions are typically not associated with neuropathy and most disappear on repeated MRI 1 - 3 months after ablation.

[0287] The success of the acute procedure (defined as confirming entry block in all treated PVs) was achieved in all 52 patients who underwent ablation. Only 2 cases of PAE were reported (pseudoaneurysm and asymptomatic thromboembolism), and there were no reported deaths, or instances of atrial-esophageal fistula, stroke / cardiovascular accident, transient ischemic attack, PV stenosis, phrenic nerve paralysis, or cardiac tamponade.

[0288] The ability to ablate safely at very high power and for a short duration has several theoretical advantages. First, the contact stability between the catheter and the tissue is thought to be an important factor contributing to clinical success. A sufficient minimum CF is necessary to enable contact so that recurrent arrhythmias are not long-lasting, but a CF that is too high may cause immediate complications such as steam pops or thrombi due to atrial perforation. During the test ablation, since lesions are created in a very short time before stability is considered, the adverse effects of CF instability can be reduced. In fact, in preclinical trials, the quality of the lesions appears more homogeneous compared to standard ablation. Naturally, the greater the degree of instability, the more the effectiveness of further test ablation modes can be reduced or impaired by the lesions caused by catheter 28.

[0289] Second, an important safety consideration for AF ablation is to minimize damage to collateral tissue. In preclinical models, it has been suggested that test ablation minimizes conductive heating and resultant damage to collateral tissue such as the esophagus and, in some cases, minimizes the risk of atrial-esophageal fistula. The absence of atrial-esophageal fistula was promoted in this study. Indeed, the single case of esophageal ulcerative bleeding observed in this study reveals that care must be maintained to ensure that the complication rate does not increase even with the use of the test ablation mode strategy.

[0290] The overall incidence of thrombus observed using catheter 28 in the test ablation mode was clinically similar to control catheter 1 and was shown to be significantly less compared to control catheter 2. The overall incidence of steam pop observed using catheter 28 in the test ablation mode was clinically equivalent compared to control catheters 1 and 2. Lesion characteristics were clinically similar between catheter 28 and the control catheters. The overall performance of catheter 28 in the test ablation mode was clinically similar to or better than control catheters 1 and 2 in the power control ablation mode.

[0291] The overall safety and performance, including endpoints such as thrombus and steam pop of catheter 28 when used in the test ablation mode, were shown to be clinically similar compared to control catheters 1 and 2 when used in the power control mode. The maximum ablation parameters identified for catheter 28 in the test ablation mode were tested and evaluated to be clinically safe and clinically effective based on the results of this test.

[0292] No carbides / clots were observed on catheter 28. The overall incidence of steam pops observed using catheter 28 (0 in the RA, 5 / 9 in the LV, 0 at all other locations) was lower compared to control catheter 1 (0 in the RA, 3 / 36 between PVIs, 5 / 12 on the LA wall, 5 / 6 in the LV, 1 / 7 in the RV). Importantly, the incidence of steam pop occurrence in both left atrial ablation and right atrial ablation using catheter 28 in the test ablation mode in the test setting was zero.

[0293] In this study, when used in its test ablation mode, catheter 28 was able to produce clinically effective electrogram signal attenuation and clinically equivalent or better lesions compared to control catheter 1 in all four cardiac chambers. The generator used in connection with catheter 28 was also shown to be able to successfully modify the irrigation flow based on the electrode temperature response and power settings of catheter 28 to maintain the temperature limits when used in the test ablation mode. Catheter 28 using the test ablation mode with temperature targets and flow settings was shown to meet all acceptance criteria. The overall functionality and clinical safety of catheter 28 using the test ablation mode were proven to be clinically equivalent or better than those of control catheter 1.

[0294] In this study, when tested in both vertical and parallel orientations, there was no significant difference in the overall incidence of clots observed with catheter 28 using the test ablation mode compared to control catheter 1 in the power control mode. In conclusion, this study of catheter 28 demonstrated its clinical feasibility and associated safety.

[0295] In the second test, the catheter 28 of the present disclosure was evaluated in a temperature-controlled 90W-4 second ablation mode applied to the thigh muscle and beating heart models in six dogs having an average body weight of about 21.9 kilograms, as shown in FIG. 30A. In this test, as shown in FIG. 30B, an optical temperature sensor was placed in the thigh muscle of each patient about 3 mm below the catheter tip to compare the tissue temperature trend and heating pattern between one ablation and two ablations. The depth of the lesion was measured according to RF application. Various sized lesion tags were used to test and examine the integrity of the RA linear lesions and any gaps between the lesions in the beating heart of the dog.

[0296] In the second test, it was observed that two 90W-4S applications with a 4-second interruption period caused a further tissue temperature increase ranging from 67.5°C to 76.3°C, as seen in FIG. 31A. The second test also resulted in lesions deeper than 40% in both the beating heart and thigh muscle, as seen in FIG. 31B, without any observed carbonization, clotting, or steam pops. Also, overall pathology showed that when using 2 mm RF tags, overlapping continuous RF damage lines were generated. A gap was detected in the damage line when using 4 mm RF tags, and similarly, when using 3 mm tags, continuous damage lines were formed with minimal overlapping lesions. Therefore, in the second test, it was concluded that when using 3 mm lesion tags and a point-by-point "sealing" ablation approach, 90W-4S formed continuous and transmural linear damage lines on the atrial wall with minimal overlap of the lesions. Intentionally overlapping 90W-4S applications intentionally formed deeper lesions.

[0297] FIG. 32 depicts a schematic overview of a method 3200 according to the present disclosure. The method 3200 can include selectively positioning a diagnostic catheter at a treatment site within a vasculature structure (3210), selectively positioning an ablation catheter system at the treatment site according to any of the previous claims (3220), performing PVI by ablating tissue at the treatment site using the ablation catheter system (3230), and clinically improving all fluids delivered via an intravenous line by the ablation catheter system during an ablation procedure by the ablation catheter system (3240).

[0298] FIG. 33 depicts a schematic overview of a method 3300 according to the present disclosure. The method 3300 can include inserting an ablation catheter system according to any of the previous claims at a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor proximate within the body (3310), ablating the cardiac tissue using the ablation catheter system (3320), and achieving complete pulmonary vein isolation by the ablation catheter system for all patients in a given population of patients suffering from PAF (3330).

[0299] FIG. 34 depicts a schematic overview of a method 3400 according to the present disclosure. The method 3400 includes inserting an ablation catheter system according to any of the preceding claims into a body of a living being (3410), actuating the ablation catheter system to contact heart tissue within the body (3420), generating ablation energy at a power output level at a certain current level (3430), transmitting the generated energy into the tissue via the ablation catheter system (3440), ablating the heart tissue using the ablation catheter system (3450), and clinically improving safety and efficacy by the ablation catheter system (3460), resulting in improving such that the RF ablation time is at least about 80% less compared to the ablation time of previously clinically approved catheter systems for PAF.

[0300] FIG. 35 depicts a schematic overview of a method 3500 according to the present disclosure. The method 3500 may include selectively positioning a diagnostic catheter at a treatment site within a vasculature (3510), selectively positioning an ablation catheter system according to any of the preceding claims at the treatment site (3520), performing PVI by ablating tissue at the treatment site using the ablation catheter system (3530), and clinically improving safety and efficacy of PAF by a contact force acting in a range of about 5 to 30 grams between the ablation catheter system and a target site by the ablation catheter system (3540).

[0301] FIG. 36 depicts a schematic overview of a method 3600 according to the present disclosure. The method 3600 may include inserting (3610) an ablation catheter system according to any of the previous claims into a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor proximate to the body within; ablating (3620) the cardiac tissue using the ablation catheter system; and achieving (3630) clinically improved safety and efficacy for PAF with a significantly shorter total treatment time, ablation time, fluoroscopy time, and RF application time.

[0302] FIG. 37 depicts a schematic overview of a method 3700 according to the present disclosure. The method 3700 may include inserting (3710) an ablation catheter system according to any of the previous claims into a body of a living being; actuating (3720) the ablation catheter system to contact cardiac tissue within the body; generating (3730) ablation energy at a power output level at a certain current level; transmitting (3740) the generated energy into the tissue via the ablation catheter system; ablating (3750) the cardiac tissue using the ablation catheter system; and achieving (3760) zero occurrence of steam pop in both left atrial ablation and right atrial ablation using the ablation catheter system at a power setting including a predefined irrigation flow rate and 90 W.

[0303] FIG. 38 depicts a schematic overview of a method 3800 according to the present disclosure. The method 3800 may include selectively positioning (3810) an ablation catheter system at a treatment site; and ablating (3820) tissue at the treatment site with the ablation catheter system using a power setting of about 90 W applied to the tissue in about 4-second increments with an interruption period of about 4 seconds during the application.

[0304] FIG. 39 depicts a schematic overview of a method 3900 according to the present disclosure. Method 3900 may include delivering (3910) an ablation catheter system to a treatment site including cardiac tissue, the system including at least one electrode and at least one sensor proximate to the other, ablating (3920) the cardiac tissue with the ablation catheter system at a power setting including a predetermined irrigation flow rate and about 90 W, and achieving (3930) an occurrence rate of about zero steam pops and complete pulmonary vein isolation in both left atrial ablation and right atrial ablation with the ablation catheter system for all patients in a given patient population suffering from PAF.

[0305] The methods, systems, and devices of the present disclosure have illustrated a clinically effective and / or safe mapping catheter system for use in patients having a particular condition such as PAF. The particular configuration, material selection, and size and shape of the various elements may be changed according to the particular design specifications or constraints required by the system or method constructed according to the principles of the disclosed technology. Such changes are intended to be encompassed within the scope of the disclosed technology. Accordingly, the embodiments disclosed herein are considered to be illustrative rather than limiting in every respect. Thus, while particular forms of the present disclosure have been illustrated and described above, various modifications may be made without departing from the spirit and scope of the present disclosure, and it will be apparent that any change within the meaning and range of the equivalents thereof is intended to be embraced by the present disclosure.

[0306] 〔Embodiments〕 (1) An ablation catheter system for drug - refractory symptomatic paroxysmal atrial fibrillation (PAF), an elongated body, an electrode assembly coupled to the elongated body, the electrode assembly comprising a shell configured with an inner chamber and a wall defining a proximal portion and a distal portion, the wall of the distal portion having at least one opening, A microelement extending through the inner chamber between the proximal portion and the distal portion, having a distal end received within the at least one opening, the distal end having at least the same extent as the outer surface of the wall, the microelement; The system is configured to comprise an ablation mode including a power setting of about 90 W applied to tissue in about 4-second increments with an interruption period of about 4 seconds during application. (2) The system according to embodiment 1, wherein the ablation mode is configured to cause a maximum tissue temperature of about 76°C. (3) The system according to embodiment 1, further comprising a perfusion pump configured to deliver an infusion of a treatment solution by and through the elongated body. (4) The system according to embodiment 3, wherein the perfusion pump is configured to deliver a treatment solution at about 2 milliliters per minute when high-frequency energy is not being delivered during high-frequency ablation. (5) The system according to embodiment 3, wherein the perfusion pump is configured to deliver a treatment solution at about 8 milliliters per minute when high-frequency energy is not being delivered during high-frequency ablation.

[0307] (6) The system according to embodiment 1, further comprising a force sensing system for detecting a contact force applied to the treatment site by the catheter system during use, the contact force between the system and the target site ranging from about 5 to 30 grams. (7) The system according to embodiment 1, wherein the system is configured to achieve a zero incidence rate of steam pops in both left atrial ablation and right atrial ablation using the ablation mode. (8) The system according to embodiment 1, wherein the ablation mode is configured to increase the maximum tissue temperature by at least about 13% between a first ablation application and a second ablation application. (9) The ablation mode is configured to deepen the damaged area by about 40% between the first ablation application and the second ablation application, and the ablation mode further includes a contact force ranging from about 10 to 30 grams between the ablation catheter system and the target site, the system according to Embodiment 1. (10) The ablation mode is configured to deepen the damaged area by about 40% between the first ablation application and the second ablation application, and to avoid the formation of carbides, clots, and steam pops, the system according to Embodiment 1.

[0308] (11) The ablation mode is configured for a point-by-point "kiss" ablation approach that minimizes overlap of the damaged areas and creates continuous and transmural linear damage lines in the atrial wall, the system according to Embodiment 1. (12) The ablation mode includes temperature control and a perfusion link, the system according to Embodiment 1. (13) The electrode assembly includes one or more ring electrodes and microelectrodes, and the catheter system is configured to clinically improve the pacing from the one or more ring electrodes and microelectrodes during the idle state and during high-frequency ablation, the system according to Embodiment 1. (14) The system is configured to achieve a high-frequency ablation time that is at least about 80% lower than the ablation time of a previously clinically approved catheter system for treating PAF, the system according to Embodiment 1. (15) The distal end of the microelement includes an exposed portion outside the wall of the shell, and the microelement is configured for temperature sensing, the system according to Embodiment 1.

[0309] (16) The microelement further includes a first plurality of first microelements configured for impedance sensing and a second plurality of second microelements configured for temperature sensing, the system according to Embodiment 1. (17) The system according to embodiment 16, wherein the distal ends of the first micro-elements are arranged in a radial pattern along the outer periphery of the distal portion of the shell, centered on the longitudinal axis of the electrode assembly. (18) A system comprising: an elongated body; an electrode assembly coupled to the elongated body, the electrode assembly comprising an inner chamber and a wall defining a proximal portion and a distal portion, the wall having at least one opening; a micro-element extending through the inner chamber between the proximal portion and the distal portion; The system is configured to have an ablation mode that includes a power setting of about 90 W applied to tissue in about 4-second increments to achieve an incidence of steam pop generation of approximately zero and complete pulmonary vein isolation in both left atrial ablation and right atrial ablation. (19) The system according to embodiment 18, wherein the ablation mode is configured to produce a continuous and transmural linear lesion line in the atrial wall with a minimal overlap of lesions, with a "kiss" ablation approach point by point. (20) The system according to embodiment 18, wherein the ablation mode is configured to cause a maximum tissue temperature of about 76°C.

Claims

1. An ablation catheter system for pulmonary vein isolation in drug - refractory symptomatic paroxysmal atrial fibrillation (PAF), comprising: an elongated body; an electrode assembly coupled to the elongated body, the electrode assembly comprising a shell configured with an inner chamber and a wall defining a proximal portion and a distal portion, the wall of the distal portion having at least one opening; a micro - element extending through the inner chamber between the proximal portion and the distal portion, the micro - element having a distal end received within the at least one opening, the distal end having at least the same spread as the outer surface of the wall; an RF generator; a processor; and comprising: The processor of the system is configured to create a continuous and transmural linear lesion line in the atrial wall and minimize the overlap of lesions at each point constituting the linear lesion line, with a 4 - second interruption period between applications and a 4 - second interval, including a power setting of 90 W applied from the RF generator to the tissue of the atrial wall, and is configured with an ablation mode.

2. The system according to claim 1, wherein the ablation mode is configured to cause a maximum tissue temperature of 76°C.

3. The system according to claim 1, further comprising a perfusion pump configured to deliver the infusion of a therapeutic solution by and through the elongated body.

4. The system according to claim 3, wherein the perfusion pump is configured to deliver a therapeutic solution at 2 milliliters per minute when high - frequency energy is not being delivered during high - frequency ablation.

5. The system according to claim 1, further comprising a force - sensing system for detecting the contact force applied to the atrial wall by the system during use, wherein the contact force between the system and the target site ranges from 5 to 30 grams.

6. The system according to claim 1, wherein the system is configured to achieve a zero incidence rate of steam pops using the ablation mode.

7. The system according to claim 1, wherein the ablation mode is configured to increase the maximum tissue temperature by at least 13% between a first ablation application and a second ablation application.

8. The ablation mode is configured to make the damaged part 40% deeper between the first ablation application and the second ablation application, and the ablation mode further includes a contact force ranging from 10 to 30 grams between the system and the target site, the system according to claim 1.

9. The ablation mode is configured to make the damaged part 40% deeper between the first ablation application and the second ablation application, and to avoid the formation of carbides, clots, and steam pops, the system according to claim 1.

10. The distal end of the microelement includes an exposed portion outside the wall of the shell, and the microelement is configured for temperature sensing, the system according to claim 1.

11. The microelement further includes a first plurality of first microelements configured for impedance sensing and a second plurality of second microelements configured for temperature sensing, the system according to claim 1.

12. The distal ends of the first microelements are arranged in a radial pattern along the outer periphery of the distal portion of the shell around the longitudinal axis of the electrode assembly, the system according to claim 11.

13. An ablation catheter system for pulmonary vein isolation in drug - refractory symptomatic paroxysmal atrial fibrillation (PAF), An elongated body, An electrode assembly coupled to the elongated body, the electrode assembly comprising an inner chamber and a wall defining a proximal portion and a distal portion, the wall having at least one opening, A microelement extending through the inner chamber between the proximal portion and the distal portion, An RF generator, A processor, Including, The processor of the system is configured to have an ablation mode that produces a continuous and transmural linear damage line in the atrial wall and includes a 90 W power setting applied from the RF generator to the tissue of the atrial wall at 4 - second intervals with a 4 - second interruption period during the application to minimize the overlap of the damaged parts at each point constituting the linear damage line.

14. The ablation mode is configured to cause a maximum tissue temperature of 76°C, the system according to claim 13.

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