CN113038895A - System for ablating cardiac tissue - Google Patents

Abstract

The presently disclosed subject matter includes systems, devices, and methods for treating paroxysmal atrial fibrillation in a predetermined patient population, the method including ablating one or more pulmonary vein-targeted tissue with one or more of a plurality of electrodes of an independently controlled multi-electrode radio frequency balloon catheter, the balloon catheter including a plurality of electrodes for radio frequency ablation that are independently controllable; determining a predictor of single-freeze Pulmonary Vein Isolation (PVI) success rate based on ablation parameters of the balloon catheter; and achieving a single cryo-isolation PVI success rate in isolation of all targeted pulmonary veins of a predetermined patient population based on the predictor and the ablation tissue step.

Description

System for ablating cardiac tissue

Priority and cross-reference to related applications

The present application claims priority from 35 USCs 119 and 365 (and paris convention) to: U.S. provisional patent application No. 62/731,525 (attorney docket No. BIO6040USPS 1; 253757.000003), filed on 14.9.2018; U.S. provisional patent application No. 62/754,275 (attorney docket No.: BIO6039USPSP 1; 253757.000002), filed on 11/1/2018; U.S. provisional patent application No. 62/771,896 (attorney docket No. BIO6079USPSP 1; 253757.000004), filed on 27.11.2018; U.S. provisional patent application No. 62/886,729 (attorney docket No. BIO6039USPSP 3; 253757.000013), filed on 14/8/2019; and U.S. provisional patent application No. 62/889,471 (attorney docket No. BIO6039USPSP 4; 253757.000014), filed on 20/8/2019; and U.S. provisional patent application No. 62/873,636 (attorney docket No. BIO6039USPSP 2; 253757.000008), filed on 12.7.2019; and U.S. patent application serial No. 16/569608 (attorney docket No. BIO6079 USNP; 1253757.000010), filed on 12.9.9.2019. The contents of these prior U.S. patent applications in this paragraph are incorporated by reference herein in their entirety as if shown verbatim.

Technical Field

The present disclosure relates to medical devices designed to treat cardiac arrhythmias.

Background

When a region of cardiac tissue abnormally conducts electrical signals to adjacent tissue, an arrhythmia, such as Atrial Fibrillation (AF), may occur. This disrupts the normal cardiac cycle and leads to arrhythmia. There are certain procedures for treating cardiac arrhythmias that involve surgically destroying the origin of the arrhythmia-causing signal and destroying the conduction pathway for such signal. By applying energy through a catheter to selectively ablate cardiac tissue, it is sometimes possible to stop or alter the propagation of unwanted electrical signals from one part of the heart to another. The ablation method breaks the unwanted electrical path by forming a non-conductive ablation lesion.

In this regard, it is understood that AF is the most common persistent arrhythmia in humans. Its incidence in the general population is anywhere from 0.4% to 1%, and prevalence increases with age to about 10% in patients over 80 years of age. The main clinical benefit of AF ablation is to improve quality of life due to the elimination of arrhythmia-related symptoms such as palpitations, fatigue, or intolerance of effort.

However, due to differences in human anatomy, ostial and tubular regions in the heart have a wide variety of sizes. Thus, conventional balloons or inflatable catheters, while having sufficient structural support to be in effective circumferential contact with tissue, may not have the necessary flexibility to accommodate different shapes and sizes. In particular, ablation electrodes that provide greater surface contact may lack sufficient flexibility. Furthermore, precision wires (such as those of electrode leads and/or thermocouple wires) and their solder joints require support and protection from breakage and damage during both assembly and use within a patient. In addition, because the balloon configuration is radially symmetric and the plurality of electrode elements surround the balloon configuration, orienting the balloon electrode assembly under fluoroscopy also presents challenges.

Disclosure of Invention

Accordingly, the inventors of the present disclosure have recognized a need for a balloon or catheter having an inflatable member with contact electrodes that can contact more tissue areas while maintaining sufficient flexibility to accommodate different anatomies and tighter spatial constraints of the ostium and pulmonary veins. The inventors have recognized that there is a need for a balloon catheter to carry an electrode assembly with accommodation for the ostium and pulmonary veins that can be manufactured from a universal flex circuit. The following balloon catheters are also needed: it can have a variety of functions, including diagnostic and therapeutic functions, such as ablation, pacing, navigation, temperature sensing, electrical potential sensing and impedance sensing, and is suitable for use with other catheters, including lasso catheters or focal catheters.

The solution of the present disclosure solves these and other problems in the art.

The subject matter of the present disclosure is to treat paroxysmal and/or drug refractory atrial fibrillation using a multi-electrode radio frequency balloon catheter and a multi-electrode diagnostic catheter to achieve at least one of a predetermined clinical effectiveness and an acute effectiveness for a predetermined population size. The inventors believe that there are theoretical advantages to combining a multi-electrode rf balloon catheter with the multi-electrode diagnostic catheter of the present disclosure, including a high probability of single-shot pulmonary vein isolation with minimal collateral damage to non-pulmonary vein structures, but without the drawbacks of excessive heating or cooling of surrounding tissue. In some examples, a multi-electrode rf balloon of a multi-electrode rf balloon catheter is configured to deliver directionally tailored energy using multiple electrodes, thereby optimizing safety and/or efficacy. In particular, examples of the present disclosure are suitable for isolating atrial pulmonary veins when treating a subject with paroxysmal atrial fibrillation.

In some examples, a method or use for treating paroxysmal atrial fibrillation in a predetermined patient population is disclosed. The method or use may include ablating one or more pulmonary vein-targeted tissues with one or more of a plurality of electrodes of an independently controlled multi-electrode radio frequency balloon catheter, the balloon catheter including a plurality of electrodes for radio frequency ablation that are independently controllable; determining a characteristic of single-freeze Pulmonary Vein Isolation (PVI) success rate based on an ablation parameter of a balloon catheter; and achieving a single cryo-isolation PVI success rate in isolation of all targeted pulmonary veins of a predetermined patient population based on the characteristics and the ablating tissue step.

In some examples, the step of achieving a single cryo-isolated PVI success rate includes further ablating one or more tissues targeting the pulmonary veins with one or more of the plurality of electrodes based on the characteristic.

In some examples, the step of achieving a single cryo-isolated PVI success rate includes ceasing further ablation of tissue with the multi-electrode radio frequency balloon catheter based on the characteristic.

In some examples, the step of achieving a single cryo-isolated PVI success rate comprises achieving a success rate of at least about 91.7% by ablating with a pre-ablation average initial impedance of less than about 95 Ω.

In some examples, the step of achieving a single cryo-isolated PVI success rate comprises achieving a success rate of at least about 91.7% by ablating with a highest pre-ablation initial impedance of less than about 100 Ω.

In some examples, the step of achieving a single cryo-isolated PVI success rate comprises achieving a success rate of at least about 87% by ablating with a pre-ablation initial anterior wall impedance of less than about 95 Ω.

In some examples, the step of achieving a single cryo-isolated PVI success rate comprises achieving a success rate of at least about 85% by ablating with a pre-ablation minimum initial anterior wall impedance of between about 80 Ω to 90 Ω.

In some examples, the step of achieving a single cryo-isolated PVI success rate comprises achieving a success rate of at least about 88% by ablating with a pre-ablation highest initial anterior wall impedance of about 110 Ω.

In some examples, the step of achieving a single cryo-isolated PVI success rate comprises achieving a success rate of at least about 87.5% by ablating with a pre-ablation initial anterior wall impedance change impedance range of less than about 20 Ω.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which limits the maximum initial temperature among the electrodes of the balloon catheter to less than about 31 ℃.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which allows for a minimum anterior wall impedance approximately between about 80 Ω to 90 Ω.

In some examples, the step of achieving a single freeze isolated PVI success rate comprises achieving a success rate of at least about 90% by ablating with an average initial impedance of less than about 95 Ω and a highest initial impedance of less than about 110 Ω.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which is the initial temperature and initial impedance at the lesion site immediately prior to the ablation step.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which is a relatively low initial temperature (about 31 degrees celsius or less) immediately prior to the ablation step. The term "relatively low initial temperature" includes temperatures below body temperature, and in one embodiment, includes temperatures of about 31 degrees celsius or less.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which is an initial temperature in a relatively low range at the lesion site immediately prior to the ablation step, with the highest and lowest impedances measured initially (prior to ablation) from the electrodes being no more than 20 to 30 ohms (and preferably 20 ohms or less) apart (i.e., the impedances measured from all electrodes differ from each other by only 20 to 30 ohms (or less than 30 ohms)).

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which is an initial impedance having a relatively high value with a relatively narrow range.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which is an absolute value of an impedance reading within a predetermined range.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate before and during ablation, which is the electrode temperature before and during ablation.

In some examples, the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being an average initial temperature, and wherein the average initial temperature is approximately less than about 28 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed initial temperature, and wherein the distributed initial temperature is approximately greater than about 31 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed initial temperature, and wherein the distributed initial temperature is approximately greater than about 30 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed initial temperature, and wherein the distributed initial temperature is approximately greater than about 29 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature slope, and wherein the pre-ablation minimum temperature slope is approximately greater than about 0.75 ℃/s, and the single cryo-isolation PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature, and wherein the pre-ablation minimum temperature is approximately greater than about 6 ℃, and the single cryo-isolation PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single freeze-isolation PVI success rate prior to ablation, the predictor being a pre-ablation maximum initial temperature, and wherein the pre-ablation maximum initial temperature is approximately less than about 31 ℃, and the single freeze-isolation PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a pre-ablation initial temperature variation, and wherein the pre-ablation initial temperature variation is approximately less than about 3 ℃, and the single cryo-isolation PVI success rate is approximately at least about 95%.

In some examples, the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation initial impedance variation, and wherein the pre-ablation initial impedance variation comprises an optimal range of approximately less than about 20 Ω, and the single freeze isolated PVI success rate is approximately at least about 88.5%.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a pre-ablation minimum impedance dip, and wherein the pre-ablation minimum impedance dip is approximately greater than about 12 Ω, and the single cryo-isolation PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a pre-ablation impedance dip change, and wherein the pre-ablation impedance dip change is approximately greater than about 20 Ω and the single cryo-isolation PVI success rate is approximately at least about 85%.

In some examples, the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation minimum impedance reduction percentage, and wherein the pre-ablation minimum impedance reduction percentage is approximately greater than or equal to about 12%, and the single freeze isolation PVI success rate is approximately at least about 90%.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a pre-ablation impedance drop percentage change, and wherein the pre-ablation impedance drop percentage change is less than about 20 Ω, and the single cryo-isolation PVI success rate is approximately at least about 85%.

In some examples, the single freeze isolation PVI success rate is approximately about 92% when the number of electrodes having an initial impedance deviation from the average is zero.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, which is the difference in impedance between the anterior and posterior walls.

In some examples, the difference is approximately less than about 20 Ω for a predetermined patient population, and the single-freeze PVI success rate is approximately at least about 85%.

In some examples, the difference is approximately less than about 20 Ω for a predetermined patient population of at least 25 patients, and the single-freeze PVI success rate is approximately at least about 85%.

In some examples, the difference is approximately between 20 Ω to 30 Ω for a predetermined patient population, and the single-freeze PVI success rate is approximately at least about 78%.

In some examples, the difference is approximately between 20 Ω to 30 Ω for a predetermined patient population of at least 75 patients, and the single-freeze PVI success rate is approximately at least about 78%.

In some examples, the difference is approximately between 30 Ω to 40 Ω for a predetermined patient population, and the single-freeze PVI success rate is approximately at least about 75%.

In some examples, the difference is approximately between 30 Ω to 40 Ω for a predetermined patient population of at least 60 patients, and the single-freeze PVI success rate is approximately at least about 75%.

In some examples, the difference is approximately between 40 Ω to 50 Ω for a predetermined patient population, and the single-freeze PVI success rate is approximately at least about 67%.

In some examples, the difference is approximately between 40 Ω to 50 Ω for a predetermined patient population of at least 34 patients, and the single-freeze PVI success rate is approximately at least about 67%.

In some examples, the difference is approximately between 50 Ω to 60 Ω for a predetermined patient population, and the single-freeze PVI success rate is approximately at least about 35%.

In some examples, the difference is approximately between 50 Ω to 60 Ω for a predetermined patient population of at least 11 patients, and the single-freeze PVI success rate is approximately at least about 35%.

In some examples, the difference is approximately greater than about 60 Ω for a predetermined patient population, and the single-freeze PVI success rate is approximately at least about 33%.

In some examples, the difference is approximately greater than about 60 Ω for a predetermined patient population of at least 9 patients, and the single-freeze PVI success rate is approximately at least about 33%.

In some examples, the balloon catheter is a full circumferential full electrode combustion ablation catheter.

In some examples, the step of ablating the tissue lasts 60 seconds.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation average initial impedance is the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation initial impedance change is the predictor.

In some examples, the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the post-ablation minimum impedance falls to the assessment factor.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation impedance drop varies as the evaluation factor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein post-ablation average temperature slope is the evaluation factor.

In some examples, the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein a post-ablation minimum temperature slope is a predictor factor.

In some examples, the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation average temperature rise is the assessment factor.

In some examples, the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation coldest temperature rises to the assessment factor.

In some examples, the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the post-ablation minimum impedance reduction percentage is the assessment factor.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein a post-ablation impedance drop percentage varies as the evaluation factor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation minimum impedance falls to the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation initial temperature change is the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation maximum initial impedance is the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation average initial anterior wall impedance is the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation lowest anterior wall impedance is the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation maximum anterior wall impedance is the predictor.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation anterior wall impedance variation is the predictor.

In some examples, the impedance value is an impedance value among the electrodes of the front wall.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～～4.367-0.420ΔT₀-0.0486ΔZ₀

wherein Δ T₀Is the initial impedance change and Δ Z ₀Is the initial temperature change.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～26.78-0.576T_0max-0.0632Z_0max

wherein T is_0maxIs the maximum initial temperature and Z_0maxThe highest initial impedance.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～27.70-0.540T_0max-0.0959Z_0max

wherein T is_0maxIs the maximum initial temperature and Z_0maxThe highest initial impedance.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～9.31-0.408ΔT₀-0.0544Z_0max

wherein Δ T₀Is an initial temperature change and Z_0maxThe highest initial impedance.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～22.61-0.622T_0max-0.0626ΔZ₀

wherein T is_0maxIs the maximum initial temperature and Δ Z₀Is the initial impedance change.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～11.53-0.439ΔT₀-0.0856Z_0mean

wherein Δ T ₀Is an initial temperature change and Z_0meanIs the average initial impedance.

In some examples, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～26.52+0.013ΔT₀-0.594T_0max-0.0122ΔZ₀-0.0535Z_0maxwherein Δ T₀For initial temperature change, T_0maxAt the maximum initial temperature,. DELTA.Z₀Is an initial impedance change, and Z_0maxThe highest initial impedance.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～1.562+0.2856ΔT_min-0.0629ΔZ_drop

wherein Δ T_minIs the lowest temperature rise and Δ Z_dropIs the impedance drop change.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～-0.644+0.170ΔT_min+0.107Z_drop％_min

wherein Δ T_minIs the lowest temperature rise and Z_drop％_minIs the lowest percent impedance drop.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～0.339+0.187ΔT_min+0.0737Z_drop％_min-0.0368ΔZ_drop％

wherein Δ T_minAt the lowest temperature rise, Z_drop％_minIs the minimum percent impedance drop, and Δ Z_drop% is the percent change in impedance drop.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～1.043+0.777T′_min+0.171ΔT_min+0.0479Z_drop-min-0.0589ΔZ_drop

Wherein T'_minIs the lowest temperature slope, Δ T_minAt the lowest temperature rise, Z_drop-minIs the lowest impedance drop, and Δ Z_dropIs the impedance drop change.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～-0.507+0.206ΔT_min+0.083Z_dropmin

wherein Δ T_minIs the lowest temperature rise and Z_dropminThe minimum impedance drop.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～1.248+0.2486ΔT_min-0.0594ΔZ_drop+0.0419Z_dropmin

wherein Δ T_minIs the lowest temperature rise and Z_dropminThe minimum impedance drop.

In some examples, the characteristic is an evaluation factor of single cryo-isolation PVI success rate after ablation, and wherein the evaluation factor is determined by:

Y～1.174+0.2515ΔT_min-0.0564ΔZ_drop％

wherein Δ T_minIs the lowest temperature rise and Δ Z_dropIs the percent change in impedance drop.

In some examples, the method or use includes the step of displaying graphical representations of the individually controllable electrodes and the ablation parameters.

In some examples, one ablation parameter includes an impedance measured proximate each electrode.

In some examples, the measured impedance includes an impedance measured prior to ablation.

In some examples, the measured impedance includes an impedance measured after ablation.

In some examples, the measured impedance includes an impedance measured before ablation and an impedance measured after ablation.

In some examples, one ablation parameter includes a temperature measured proximate each electrode.

In some examples, one ablation parameter includes a maximum temperature measured proximate each electrode during ablation.

In some examples, one ablation parameter includes a temperature rise measured from the beginning of ablation to the end of ablation.

In some examples, methods or uses for treating paroxysmal atrial fibrillation in a plurality of patients are disclosed. The method or use may include delivering a multi-electrode radio frequency balloon catheter and a multi-electrode diagnostic catheter to one or more targeted pulmonary veins; ablating one or more tissues targeting the pulmonary veins using a multi-electrode radio frequency balloon catheter; diagnosing one or more targeted pulmonary veins using a multi-electrode diagnostic catheter; and achieving at least one of a predetermined clinical and acute effectiveness of the protocol based on using the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter in the isolation of the one or more targeted pulmonary veins.

In some examples, acute efficacy is defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge.

In some examples, acute effectiveness is further defined by a success rate of greater than 90% for multiple patients.

In some examples, acute effectiveness is further defined by a success rate of greater than 95% for multiple patients.

In some examples, the confidence type 1 error rate of acute and clinical effectiveness of all targeted veins is controlled at a level of about 5%. The method or use may include determining whether the procedure is clinically successful for a plurality of patients if both the acute effectiveness indication and the clinical effectiveness indication are controlled at a level of about 5%.

In some examples, the acute effectiveness is at least 80% for a plurality of at least 80 patients, 130 patients, and/or 230 patients.

In some examples, acute efficacy is further defined by confirming whether there is an entry block in all targeted pulmonary veins with the use of a focal ablation catheter after an adenosine and/or isoproterenol challenge.

In some examples, acute efficacy is further defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge without the use of a focal ablation catheter.

In some examples, the procedure is administered to a plurality of patients diagnosed with symptomatic paroxysmal atrial fibrillation.

In some examples, the predetermined effective rate is defined by the average number of rf applications per patient and the rf time required to isolate all pulmonary veins. The diagnosing step further comprises: electrophysiological mapping of the heart.

In some examples, the multi-electrode diagnostic catheter further includes a high torque shaft having a halo-shaped tip section that includes multiple pairs of electrodes that are visible under fluoroscopy.

In some examples, the predetermined acute effectiveness is defined by the absence of an ulcer in a plurality of patients after the procedure.

In some examples, the predetermined acute effectiveness is defined by a complication rate of approximately 13% or less of esophageal erythema experienced by a plurality of patients after the procedure.

In some examples, the predetermined acute effectiveness is defined by a complication rate of about 25% or less of a plurality of patients experiencing a new asymptomatic cerebral embolic lesion after the procedure.

In some examples, the predetermined acute effectiveness is defined by a complication rate of about 20% or less of a plurality of patients experiencing a new asymptomatic cerebral embolic lesion after the procedure.

In some examples, wherein the predetermined acute effectiveness is defined by a complication rate of about 5% to 9% or less of the plurality of patients experiencing the primary adverse event about 7 days or more after the procedure.

In some examples, inclusion criteria for multiple patients include a diagnosis of symptomatic paroxysmal atrial fibrillation and the ability of the patient to comply with uninterrupted on-schedule anticoagulation requirements.

In some examples, the predetermined acute effectiveness is defined by a total protocol time.

In some examples, the population size to achieve the predetermined success rate is at least 80 patients, 130 patients, 180 patients, and/or 230 patients.

In some examples, the predetermined acute effectiveness is defined by a total radio frequency application time.

In some examples, the predetermined acute effectiveness is defined by a total dwell time of the multi-electrode radio frequency balloon catheter.

In some examples, the predetermined acute effectiveness is defined by the total time to isolate all targeted pulmonary veins.

In some examples, the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radio frequency balloon catheter at each location of all targeted pulmonary veins.

In some examples, the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radio frequency balloon catheter to each patient.

In some examples, the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radio frequency balloon catheter to each targeted vein.

In some examples, a multi-electrode radio frequency balloon catheter includes a compliant balloon incorporating a plurality of electrodes configured to deliver radio frequency energy to tissue of a pulmonary vein and sense a temperature at each electrode.

In some examples, clinical effectiveness is defined by the incidence of early onset of one or more adverse events within a predetermined time of a protocol being conducted.

In some examples, the predetermined time is at least 7 days.

In some examples, the one or more adverse events include: death, atrial-esophageal fistula, myocardial infarction, cardiac packing/perforation, thromboembolism, stroke, TIA (transient ischemic attack), phrenic nerve paralysis, pulmonary vein stenosis, and large vessel access bleeding.

In some examples, the one or more adverse events include: the incidence of individual adverse events from the primary composite event; the incidence of serious adverse device effects; the incidence of severe adverse events within 7 days, at least 7 days to 30 days, and at least 30 days after the protocol; the incidence of non-serious adverse events; the incidence of asymptomatic and symptomatic cerebral embolism as determined by MRI assessment before and after ablation; and the frequency, anatomical location and size (diameter and volume) of cerebral emboli assessed by MRI at baseline, post-ablation and during follow-up.

In some examples, about 8% of the plurality of patients experienced one or more adverse events, including: NIHSS (national institute of health stroke scale) scores at baseline, post-ablation, and during follow-up; a summary of MoCA (montreal cognitive assessment) scores and mRS (modified Rankin scale) scores at baseline, 1 month, and during further follow-up; the hospitalization rate for cardiovascular events; a percentage (%) of pulmonary vein isolation supplemental ablation (touch-up) by a focal catheter among the one or more targeted veins; percent (%) of subjects with non-PV triggering using focal catheter ablation; (ii) percentage (%) of subjects with no recorded symptomatic Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left side) Atrial Flutter (AFL) episodes (> 30 seconds of episodes from day 91 to day 180 on arrhythmia monitoring device); percent (%) of subjects with no recorded Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left-sided) Atrial Flutter (AFL); one or more episodes lasting 30 seconds or more on the arrhythmia monitoring device from day 91 to day 180 after the protocol; and one or more protocol parameters including total protocol and ablation time, balloon dwell time, radio frequency application time, number of radio frequency applications, fluoroscopy time and dose.

In some examples, the acute safety rate includes a complication incidence of 10% or less and is defined by the incidence of asymptomatic cerebral embolic lesions upon discharge electromagnetic resonance imaging (MRI).

In some examples, acute effective rates include a complication rate of about 0% and are defined by the presence of esophageal injury erythema.

In some examples, the acute effective rate is 100% and is defined by electrically isolating all targeted pulmonary veins without the use of a focal ablation catheter.

In some examples, an acute effective rate is defined by determining an absence of recorded atrial fibrillation, atrial tachycardia, or atypical atrial flutter onset based on electrocardiographic data over an entire validity assessment period (1 year).

In some examples, acute effective rate is defined by pulmonary vein isolation supplemental ablation of a focal catheter among all targeted pulmonary veins.

In some examples, the predetermined clinical effectiveness rate is defined by a complication rate of 10% or less associated with the incidence of symptomatic and asymptomatic cerebral embolism after ablation as compared to before ablation.

In some examples, a multi-electrode diagnostic catheter is configured for electrophysiological recording and stimulation of an atrial region of the heart, and is used in conjunction with a multi-electrode radio frequency balloon catheter.

In some examples, methods or uses of administering a protocol for treating paroxysmal atrial fibrillation in a plurality of patients are provided. The method or use includes delivering a multi-electrode radiofrequency balloon catheter and a multi-electrode diagnostic catheter to one or more targeted pulmonary veins; and ablating all tissue targeting the pulmonary veins using the multi-electrode radio frequency balloon catheter; diagnosing all targeted pulmonary veins using a multi-electrode diagnostic catheter; and isolating all predetermined adverse event rates targeting the pulmonary veins using the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter during and about 6 months after the procedure.

In some examples, methods or uses are provided for treating paroxysmal atrial fibrillation in a plurality of patients. The method or use includes assessing the number and size of all targeted pulmonary veins and anatomical structures of the left atrium; puncturing the transseptal space; selectively positioning a multi-electrode esophageal temperature monitoring device in the vasculature relative to all targeted pulmonary veins; selectively positioning a multi-electrode radio frequency balloon catheter in the vasculature relative to all targeted pulmonary veins; selectively positioning a multi-electrode diagnostic catheter in the vasculature relative to all targeted pulmonary veins; ablating all tissue targeting the pulmonary veins using a multi-electrode radio frequency balloon catheter; confirming isolation of all targeted pulmonary veins using a multi-electrode diagnostic catheter; confirming the presence of entry blockages in all targeted pulmonary veins; based on confirming the presence of the entry block, a predetermined clinical effectiveness and/or acute effectiveness of the procedure is achieved that is associated with isolating all targeted pulmonary veins according to the procedure.

In some examples, all targeted pulmonary veins are mapped using a diagnostic catheter.

In some examples, the exclusion criteria for the plurality of patients include at least one of: atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac causes; previous surgical or catheter ablations for atrial fibrillation; ablation is expected to be received outside all targeted pulmonary vein ostia and CTI regions; previously diagnosed as having sustained, long-term atrial fibrillation and/or >7 days of continuous atrial fibrillation, or cardioversion pre-symptoms >48 hours; any Percutaneous Coronary Intervention (PCI) was performed within the last 2 months; valve repair or replacement and the presence of a prosthetic valve; any carotid stenting or endarterectomy was performed; coronary artery bypass grafting, heart surgery, heart valve surgery, or percutaneous surgery has been performed within the past 6 months; left atrial thrombus was recorded on baseline imaging; the anterior-posterior diameter of the left atrium is larger than 50 mm; the diameter of any pulmonary vein is greater than or equal to 26 mm; left ventricular ejection fraction less than 40%; anticoagulation contraindications; a history of blood clotting or bleeding abnormalities; myocardial infarction occurred within the past 2 months; thromboembolic events were recorded over the past 12 months; rheumatic heart disease; waiting for a heart transplant or other heart surgery for the next 12 months; unstable angina pectoris; acute disease or active systemic infection or sepsis; diagnosing as an atrial myxoma or an atrial septum or patch; there are implanted pacemakers, implanted cardioverter defibrillators, tissue-embedded or ferrous metal fragments; a major lung disease or any other disease or dysfunction of the lung or respiratory system that produces chronic symptoms; major congenital abnormalities; gestation or lactation; in an investigative study evaluating another device, biological agent, or drug; pulmonary vein stenosis; the presence of an intramural thrombus, tumor or other abnormality that obstructs vascular access or manipulation of the catheter; presence of an IVC filter; the presence of a disorder that obstructs vascular access; life expectancy shorter than 12 months or with other disease processes that may limit survival to shorter than 12 months; contraindications for the use of MRI contrast agents; the presence of ferrous metal debris in the patient; or an unresolved preexisting neurological deficit.

In some examples, a multi-electrode radio frequency balloon catheter includes a compliant balloon having a plurality of electrodes configured to deliver radio frequency energy to all tissue targeted to the pulmonary veins and to sense a temperature at each electrode. In some examples, the plurality of electrodes are circularly oriented to circumferentially contact the pulmonary vein ostium. In some examples, the method or use includes visualization, stimulation, recording, and ablation using a plurality of electrodes. In some examples, each electrode is configured such that the amount of power delivered to each electrode is independently controlled. In some examples, the multi-electrode radio frequency balloon catheter further comprises a proximal handle, a distal tip, and an intermediate section disposed between the proximal handle and the distal tip. In some examples, the proximal handle is a deflecting thumb knob that allows for unidirectional deflection, a balloon advancement mechanism, and a luer fitting for balloon inflation and irrigation. In some examples, the multi-electrode radio frequency balloon catheter further comprises a high torque shaft configured for rotation to facilitate precise positioning of the catheter tip to a desired site; and a deflectable end section of unidirectional weave.

In some examples, the method or use further comprises controlling perfusion of the multi-electrode radio frequency balloon catheter with a perfusion pump.

In some examples, the method or use further comprises administering uninterrupted anticoagulation therapy at least 1 month prior to the protocol.

In some examples, if a patient is receiving warfarin/coumarin therapy, the patient must have an International Normalized Ratio (INR) of ≧ 2 for at least 3 weeks prior to the procedure.

In some examples, if a patient is receiving warfarin/coumarin therapy, it must be confirmed that the patient has an International Normalized Ratio (INR) of ≧ 2 within 48 hours prior to the procedure.

In some examples, the method or use further comprises continuing anticoagulation therapy prior to the procedure.

In some examples, the method or use further comprises administering a transseptal puncture; confirm an activated clotting time target of ≧ 350 seconds prior to insertion of the multi-electrode radiofrequency balloon catheter into the left atrium, and maintain the target throughout the procedure; introducing a multi-electrode radio frequency balloon catheter; introducing a multi-electrode circular diagnostic catheter; ablating pulmonary veins with a multi-electrode radio frequency balloon catheter; determining pulmonary vein isolation in real time by using a multi-electrode circular diagnostic catheter; and confirming whether access in the pulmonary vein is blocked.

In some examples, the method or use further comprises, the multi-electrode circular diagnostic catheter comprising: an elongated body having a longitudinal axis; a distal assembly located distal to the elongate body, the distal assembly having a helical form comprising a proximal collar and a distal collar, the proximal and distal collars being angularly oriented relative to the longitudinal axis of the elongate body, and a shape memory support member extending at least through the proximal collar; at least one irrigated ablation ring electrode mounted on the proximal collar; a control handle proximal to the elongate body; and a contraction wire having a proximal end in the control handle and a distal end anchored in the proximal collar, the control handle including a first control member configured to actuate the contraction wire to contract the proximal collar, wherein the proximal collar has a first flexibility and the distal collar has a second flexibility, and the second flexibility is greater than the first flexibility.

In some examples, a method or use is provided for treating paroxysmal atrial fibrillation in a plurality of patients by applying energy to subject cardiac tissue proximate the esophagus, phrenic nerve, or lung, the method or use comprising the steps of: achieving at least one of a predetermined clinical effectiveness and an acute effectiveness of the procedure based on using a multi-electrode radio-frequency balloon catheter and a multi-electrode diagnostic catheter in the isolation of the one or more targeted pulmonary veins by positioning an expandable member proximate the left atrium, the expandable member of the multi-electrode radio-frequency balloon catheter having a longitudinal axis and including a plurality of electrodes disposed about the longitudinal axis, each electrode being independently energizable, the plurality of electrodes including a first electrode having a first radiopaque marking and a second electrode having a second radiopaque marking different from the first radiopaque marking; viewing an image of the expandable member and the first and second radiopaque markings in the left atrium; determining an orientation of the first and second radiopaque markings relative to a portion of a left atrium of the subject that is closest to an esophagus, phrenic nerve, or lung; moving one of the first and second radiopaque markers to a portion of the left atrium closest to the esophagus, phrenic nerve, or lung; energizing one or more electrodes indexed proximate to one of the radiopaque markers proximate to the portion proximate to the esophagus, phrenic nerve, or lung at a lower energization setting than the other electrodes to create a transmural lesion in the left atrium with little or no effect on adjacent anatomical structures; and electrophysiological recording and stimulation of the atrial region of tissue proximate the esophagus, phrenic nerve, or lung using a multi-electrode diagnostic catheter.

In some examples, a clinically effective device for treating atrial fibrillation in a group of patients is disclosed. The device may include an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion. The end probe may include: a first inflatable membrane coupled to the tubular member; a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane; at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and a second inflatable membrane enclosing a portion of the at least one guidewire between the second inflatable membrane and the first inflatable membrane. The device may achieve a predetermined pulmonary vein isolation efficiency rate in the group of patients.

In some examples, a clinically effective apparatus is disclosed for administering a protocol for performing cardiac electrophysiology ablation of atrial pulmonary veins and treatment of drug-refractory relapsed symptomatic pulmonary atrial fibrillation. The device may include an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion. The end probe may include: a first inflatable membrane coupled to the tubular member; a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane; at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and a second inflatable membrane enclosing a portion of the at least one lead between the second inflatable membrane and the first inflatable membrane such that each electrode of the plurality of electrodes is independently controlled to achieve a predetermined effectiveness rate of pulmonary vein isolation.

In some examples, a clinically effective apparatus is disclosed for administering a protocol for performing cardiac electrophysiology ablation of atrial pulmonary veins and treatment of drug-refractory relapsed symptomatic pulmonary atrial fibrillation. The device may include an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion. The end probe may include: a first inflatable membrane coupled to the tubular member; a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane; at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and a second inflatable membrane encapsulating a portion of the at least one lead between the second inflatable membrane and the first inflatable membrane such that each electrode of the plurality of electrodes is independently controlled to achieve pulmonary vein isolation and a safety endpoint of at least 97% within seven (7) days of successful pulmonary vein isolation.

In some examples, a clinically effective apparatus is disclosed for administering a protocol for performing cardiac electrophysiology ablation of atrial pulmonary veins and treatment of drug-refractory relapsed symptomatic pulmonary atrial fibrillation. The device may include an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion. The end probe may include: a first inflatable membrane coupled to the tubular member; a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane; at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and a second inflatable membrane encapsulating a portion of the at least one lead between the second inflatable membrane and the first inflatable membrane such that each electrode of the plurality of electrodes is independently controlled to achieve pulmonary vein isolation and a safety endpoint of at least 90% within seven (7) days of successful pulmonary vein isolation.

In some examples, the predetermined effectiveness rate includes a complication rate of 10% or less and is defined by the presence or absence of an asymptomatic cerebral embolic lesion upon discharge electromagnetic resonance imaging (MRI).

In some examples, the predetermined effective rate includes a complication rate of about 0% and is defined by the presence or absence of esophageal injury erythema.

In some examples, the predetermined effective rate is about 100% and is defined by electrically isolating all targeted pulmonary veins without the use of a focal ablation catheter.

In some examples, the predetermined effectiveness rate is defined by determining an absence of recorded atrial fibrillation, atrial tachycardia, or atypical atrial flutter episode based on electrocardiographic data over an entire effectiveness evaluation period. In some examples, the validity assessment period is about one year.

In some examples, the predetermined effective rate is defined by pulmonary vein isolation supplemental ablation of the focal catheter among all targeted pulmonary veins.

In some examples, the predetermined effectiveness rate is defined by non-PV triggering using focal catheter ablation during an index procedure.

In some examples, the predetermined effectiveness rate includes a long-term effectiveness rate.

In some examples, the predetermined effective rate is defined by the average number of rf applications per patient and the rf time required to isolate all pulmonary veins.

In some examples, the predetermined effective rate is defined by an average number of radio frequency applications per vein and a radio frequency time required to isolate a common pulmonary vein.

In some examples, the predetermined effective rate is defined by an average number of rf applications per patient and the rf time required to isolate a common pulmonary vein.

In some examples, the predetermined effectiveness rate is defined by determining a complication rate of symptomatic and asymptomatic cerebral embolism after ablation as compared to before ablation of 10% or less.

In some examples, the predetermined effectiveness rate is defined by assessing the presence of an embolism-associated neurological deficit using at least one of a NIHSS assessment and a mRS assessment.

In some examples, the end probe is configured for catheter-based cardiac electrophysiology mapping of the atrium.

In some examples, the tip probe is configured for cardiac ablation.

In some examples, an end probe includes: a plurality of electrodes coupled to the first inflatable membrane and configured to deliver radio frequency energy to tissue of the pulmonary vein and sense a temperature at each electrode.

In some examples, the plurality of electrodes are circularly oriented to circumferentially contact the pulmonary vein ostium.

In some examples, the apparatus is further configured for visualization, stimulation, recording, and ablation using a plurality of electrodes.

In some examples, each electrode is configured such that the amount of power delivered to each electrode is independently controlled.

In some examples, the end probe further comprises a proximal handle, a distal tip, and an intermediate section disposed therebetween.

In some examples, the proximal handle is a deflecting thumb knob that allows for unidirectional deflection, a balloon advancement mechanism, and a luer fitting for balloon inflation and irrigation.

In some examples, the end probe further comprises a high torque shaft configured for rotation to facilitate accurate positioning of the catheter tip to a desired site; and a deflectable end section of unidirectional weave.

In some examples, the end probe further includes a first substrate disposed on the membrane, the first substrate including a first form of a first radiopaque marking disposed thereon; and a second substrate disposed on the film, the second substrate including a second radiopaque marking of a second form disposed thereon, the second form being different from the first form.

In some examples, the device further comprises an irrigation pump to provide irrigation fluid to and out of the first inflatable membrane.

In some examples, the validity assessment period is at least 91 days after delivery of the tip probe to the pulmonary vein and ablation of tissue proximate the pulmonary vein with the tip probe.

In some examples, the validity assessment period is less than or equal to one year after delivery of the tip probe to the pulmonary vein and ablation of tissue proximate the pulmonary vein with the tip probe.

In some examples, the predetermined success rate is 60% for a population size of at least 40 patients.

In some examples, the population size to achieve the predetermined success rate is at least 300 patients, 200 patients, 100 patients, or 50 patients.

In some examples, the predetermined success rate is at least 60%.

In some examples, the predetermined success rate is determined by evaluating the patient 7 days after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

In some examples, the predetermined success rate is determined by evaluating the patient 1 month after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

In some examples, the predetermined success rate is determined by evaluating the patient 6 months after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

In some examples, the predetermined success rate is determined by evaluating the patient 12 months after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

In some examples, the predetermined success rate further comprises confirming entry block in the pulmonary vein after at least one of an adenosine challenge and an isoproterenol challenge.

In some examples, a patient suffering from at least one of the following events is considered to have unsuccessful pulmonary vein isolation, including: device or procedure related death; atrial-esophageal fistula, myocardial infarction; cardiac tamponade/perforation; thromboembolism; stroke/cerebrovascular accident (CVA); transient Ischemic Attack (TIA); phrenic nerve paralysis, pulmonary vein stenosis; pericarditis; pulmonary edema; macrovascular access complications/bleeding; and hospitalization (early or long term).

In some examples, patients suffering from at least one of the following events are considered unsuccessful pulmonary vein isolation, whereby these events may include acute procedure failure; after the blanking period (after day 90 post-index protocol), repeated ablation or surgical treatment for AF/AT/atypical (left-sided) AFL; DC cardioversion, continuous AF/AT/AFL on standard 12-lead ECG for AF/AT/atypical (left-side) AFL, even if the duration of recording is shorter than 30 seconds (after 90 days after exponential procedure); prescribing new class I and/or class III AAD for AF during the validity assessment period (91 th to 365 th days after the index protocol), or prescribing during the blanking period and the subsequent 90 elapsed days; during the effectiveness evaluation period, previously failed class I AAD and/or class III AAD (failed at or before screening) are taken at a dose greater than the highest ineffective historical dose for AF; and amiodarone was prescribed after the protocol.

In some examples, the safety endpoint is defined by a patient suffering from a primary adverse event.

In some examples, the at least one risk factor for the patient may be selected as: at least three (3) symptomatic episodes of atrial fibrillation lasting ≧ 1 minute for six (6) months prior to the device; at least one (1) episode of atrial fibrillation recorded as an electrocardiogram (e.g., Electrocardiogram (ECG), holter monitor, telemetry strip, etc.) within twelve (12) months prior to enrollment; disabling at least one (1) class I or class III AAD, as evidenced by recurrent symptomatic atrial fibrillation or intolerable side effects against AAD; an age of less than 18 years, and greater than or equal to 75 years; secondary to electrolyte imbalance; thyroid disease; reversible or non-cardiac causes; and prior surgical or catheter ablation for atrial fibrillation.

In some examples, to calculate the effectiveness, the patient has at least one of the following risk factors: patients who are known to require ablation outside the PV ostium and CTI region; atrial fibrillation previously diagnosed as having sustained or long-lasting atrial fibrillation and/or continuing atrial fibrillation 7 days after the device protocol; any percutaneous coronary intervention was performed within the past 2 months; prosthetic valve repair or replacement is performed, or a prosthetic valve is present; any carotid stenting or endarterectomy performed within the past 6 months; coronary artery bypass grafting, heart surgery or heart valve surgery has been performed within the past 6 months; left atrial thrombi were recorded within 1 day before the device protocol; the anterior-posterior diameter of the left atrium is >50 mm; left ventricular ejection fraction < 40%; anticoagulation contraindications; a history of blood clotting or bleeding abnormalities; myocardial infarction occurred within the past 2 months; thromboembolic events (including transient ischemic attacks) were recorded over the past 12 months; rheumatic heart disease; uncontrolled heart failure or New York Heart Association (NYHA) class III or IV function; waiting for a heart transplant or other heart surgery for the next 12 months; unstable angina pectoris; acute disease or active systemic infection or sepsis; diagnosis of atrial myxoma or presence of atrial septal or patches; there are implanted pacemakers or implantable cardioverter-defibrillators (ICDs); a major lung disease or any other disease or dysfunction of the lung or respiratory system that produces chronic symptoms; major congenital abnormalities; a pregnant woman; in an investigative study evaluating another device, biological agent, or drug; known pulmonary vein stenosis; the presence of an intramural thrombus, tumor or other abnormality that obstructs vascular access or manipulation of the catheter; the presence of an inferior vena cava filter; the presence of a disorder that obstructs vascular access; life expectancy shorter than 12 months or with other disease processes that may limit survival to shorter than 12 months; presenting a contraindication to the device; and the patient had been taking amiodarone at any time during the past 3 months prior to enrollment.

In some examples, if the patient is receiving warfarin/coumarin therapy, the patient must have an international normalized ratio of ≧ 2 for at least 3 weeks prior to the procedure.

In some examples, if the patient is receiving warfarin/coumarin therapy, it must be confirmed that the patient has an INR of ≧ 2 within 48 hours prior to the procedure.

In some examples, wherein anticoagulation therapy is provided prior to the procedure.

In some examples, wherein an activated clotting time of 350 to 400 seconds is targeted prior to insertion of the catheter and throughout the protocol.

In some examples, wherein the activated clotting time level is checked every 15 to 30 minutes during the protocol to ensure an activated clotting time target of 350 to 400 seconds.

In some examples, wherein the multi-electrode circular diagnostic catheter includes an elongate body having a longitudinal axis and a distal assembly located distal to the elongate body. The distal assembly may have a helical form including a proximal collar, a distal collar, and a shape memory support member extending at least through the proximal collar. The proximal and distal collars may be oriented at an angle oblique to the longitudinal axis of the elongate body; at least one irrigated ablation ring electrode mounted on the proximal collar; a control handle proximal to the elongate body; and a contraction wire having a proximal end in the control handle and a distal end anchored in the proximal collar, the control handle including a first control member configured to actuate the contraction wire to contract the proximal collar. The proximal collar may have a first flexibility and the distal collar has a second flexibility, and the second flexibility may be greater than the first flexibility.

To the accomplishment of the foregoing and related ends, certain illustrative aspects are described herein in connection with the following description and the annexed drawings. These aspects are indicative, however, of but a few of the various ways in which the principles of the claimed subject matter may be employed and the claimed subject matter is intended to include all such aspects and their equivalents. Other advantages and novel features may become apparent from the following detailed description when considered in conjunction with the drawings.

Drawings

The above and further aspects of the invention will be further discussed with reference to the following description in conjunction with the accompanying drawings, in which like reference numerals indicate like structural elements and features in the various figures. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. The drawings depict one or more implementations of the present device by way of example only and not by way of limitation.

Fig. 1 is a schematic illustration of a medical procedure using an example meter device of the present disclosure.

Fig. 2 is a top view of an exemplary catheter of the present disclosure having a balloon in an inflated state for use with a lasso catheter.

Fig. 3 is a perspective view of a multi-electrode ablation balloon catheter along with a lasso catheter that may be used in clinical studies.

Fig. 4A is an exploded perspective view of another embodiment of the balloon ablation catheter from fig. 3 showing a base balloon or first inflatable membrane having radial electrode assemblies partially covered by respective second and third inflatable membranes;

fig. 4B illustrates one embodiment of the assembled balloon ablation catheter of fig. 4A;

fig. 5 is a side view of the balloon ablation catheter of fig. 4B;

FIG. 6A is an enlarged side view of a portion of the membrane of FIG. 4A;

fig. 6B illustrates the lateral or circumferential surface area not covered by the hemispherical second and third inflatable membranes of fig. 4B.

Fig. 7 is a photograph of an actual prototype in accordance with one embodiment described and illustrated herein.

Fig. 8 is a photograph of another prototype of the embodiment described and illustrated herein.

Fig. 9 is a side view of the distal end of the catheter of fig. 2 deployed in the area of the pulmonary vein and pulmonary vein ostia.

Fig. 10 is a top plan view of an exemplary diagnostic catheter of the present disclosure.

Fig. 11 is a detailed view of the distal assembly of the diagnostic catheter of fig. 10.

Fig. 12 is a schematic cross-sectional view of a heart showing insertion of the diagnostic catheter according to fig. 10 and 11 into the left atrium.

Fig. 13 shows a schematic overview of the study of the present disclosure.

Fig. 14 shows a table summarizing recommended radiofrequency energy delivery parameters in one example.

Fig. 15 shows a table summarizing the intensity or severity of each AE evaluated according to classification.

Fig. 16 shows a table demonstrating the classification based on AAD treatments administered during and after the washout period in an exemplary study.

Fig. 17 depicts a graphical overview of one method or use according to the present disclosure.

FIG. 18 depicts a graphical overview of one method or use according to the present disclosure.

Figure 19 depicts a graphical overview of one method or use according to the present disclosure.

Fig. 20 depicts a graphical overview of one method or use according to the present disclosure.

Fig. 21 depicts a graphical overview of one method or use according to the present disclosure.

FIG. 22 depicts a graphical overview of one method or use according to the present disclosure.

Figure 23 depicts a graphical overview of one method or use according to the present disclosure.

Figure 24 shows a table summarizing single freeze isolation versus non-isolation for studies according to the present disclosure.

Fig. 25 shows a graph summarizing the initial impedance of studies according to the present disclosure.

Figure 26 shows a graph summarizing temperature rises according to studies of the present disclosure.

Fig. 27 shows a graph summarizing the impedance drops of studies according to the present disclosure.

Fig. 28 shows a graph summarizing the maximum temperatures of studies according to the present disclosure.

Fig. 29A shows a graph summarizing initial impedance changes among full circumference electrodes in the study of the present disclosure.

Fig. 29B shows a table summarizing initial impedance changes among full circumference electrodes in the study of the present disclosure.

Figure 30 shows a graph summarizing single freeze PVI rates in studies of the present disclosure.

Figure 31 shows a graph summarizing the isolation times in the study of the present disclosure.

Fig. 32 shows a graph summarizing the inflation indices in the study of the present disclosure.

Fig. 33 shows a table summarizing predictors having pre-ablation and post-ablation parameters associated with corresponding pearson-related and binary logistic regression values in studies of the present disclosure.

Fig. 34 shows a table summarizing predictors having pre-ablation parameters associated with corresponding pearson-related and binary logistic regression values in studies of the present disclosure.

Fig. 35 shows a table summarizing predictors having post-ablation parameters associated with corresponding pearson-related and binary logistic regression values in studies of the present disclosure.

Fig. 36 shows a table summarizing a ranking of pre-ablation and post-ablation parameters, which are single-freeze predictors observed in the studies of the present disclosure.

Fig. 37 shows a graph summarizing the correlation between the mean initial impedance and the age of the patient in the study of the present disclosure.

Fig. 38 shows a graph summarizing the correlation between the mean initial impedance and the Body Mass Index (BMI) of patients in the study of the present disclosure.

Fig. 39 shows a graph summarizing the correlation between initial temperature and temperature rise in the study of the present disclosure.

Fig. 40 shows a graph summarizing the correlation between initial temperature and temperature slope in the study of the present disclosure.

Fig. 41 shows a graph summarizing the correlation between the initial temperature and the initial impedance in the study of the present disclosure.

Fig. 42 shows a graph summarizing the correlation between initial temperature and resistance drop in the study of the present disclosure.

Fig. 43 shows a graph summarizing the correlation between the initial temperature change and the highest initial temperature in the study of the present disclosure.

Fig. 44 shows a graph summarizing the correlation between the initial temperature change and the impedance drop change in the study of the present disclosure.

Fig. 45 shows a graph summarizing the correlation between the initial temperature change and the temperature rise change in the study of the present disclosure.

Fig. 46 shows a graph summarizing the correlation between initial temperature change and temperature slope change in the study of the present disclosure.

Fig. 47 shows a graph summarizing the correlation between initial impedance and temperature rise in the study of the present disclosure.

Fig. 48 shows a graph summarizing the correlation between initial impedance and temperature slope in the study of the present disclosure.

Fig. 49 shows a graph summarizing the correlation between initial impedance and impedance drop in the study of the present disclosure.

Fig. 50 shows a graph summarizing the correlation between initial impedance and percentage of impedance drop in studies of the present disclosure.

Fig. 51 shows a graph summarizing the correlation between the initial impedance change and the initial temperature change in the study of the present disclosure.

Fig. 52 shows a graph summarizing the correlation between the initial impedance change and the impedance drop change in the study of the present disclosure.

Fig. 53 shows a graph summarizing the correlation between the initial impedance change and the highest initial impedance in the study of the present disclosure.

Fig. 54 shows a graph summarizing the correlation between the initial impedance change and the average initial impedance in the study of the present disclosure.

Fig. 55 shows a graph summarizing the correlation between the initial impedance change and the lowest impedance drop in the study of the present disclosure.

Fig. 56 shows a graph summarizing the correlation between the lowest temperature rise and the lowest impedance drop in the study of the present disclosure.

Fig. 57 shows a graph summarizing the correlation between the lowest impedance drop and the lowest temperature slope in the study of the present disclosure.

Fig. 58 shows a graph summarizing the correlation between the lowest temperature rise and the lowest temperature slope in the study of the present disclosure.

Figure 59 shows a schematic summarizing correlated datasets for single freeze-isolation predictors studied according to the present disclosure.

Figure 60 shows a schematic summarizing correlated datasets for single freeze isolation assessment factors according to a study of the present disclosure.

FIG. 61A illustrates a computer simulation model that performs an exemplary predictor function.

FIG. 61B shows a table summarizing data associated with the simulation of FIG. 61A.

FIG. 61C shows a table summarizing data associated with the simulation of FIG. 61A.

FIG. 62A illustrates a computer simulation model that performs an exemplary predictor function.

FIG. 62B shows a table summarizing data associated with the simulation of FIG. 62A.

FIG. 62C shows a table summarizing data associated with the simulation of FIG. 62A.

FIG. 63A illustrates a computer simulation model that performs an exemplary predictor function.

FIG. 63B shows a table summarizing data associated with the simulation of FIG. 63A.

FIG. 63C shows a table summarizing data associated with the simulation of FIG. 63A.

FIG. 64A illustrates a computer simulation model that performs an exemplary predictor function.

FIG. 64B shows a table summarizing data associated with the simulation of FIG. 64A.

FIG. 64C shows a table summarizing data associated with the simulation of FIG. 64A.

FIG. 65A illustrates a computer simulation model that performs an exemplary predictor function.

FIG. 65B shows a table summarizing data associated with the simulation of FIG. 65A.

FIG. 65C shows a table summarizing data associated with the simulation of FIG. 65A.

FIG. 66A illustrates a computer simulation model that performs an exemplary predictor function.

FIG. 66B shows a table summarizing data associated with the simulation of FIG. 66A.

FIG. 66C shows a table summarizing data associated with the simulation of FIG. 66A.

FIG. 67 shows a table summarizing data associated with another simulation.

FIG. 68A illustrates a computer simulation model that performs an exemplary evaluation factor function.

FIG. 68B shows a table summarizing data associated with the simulation of FIG. 68A.

FIG. 68C shows a table summarizing data associated with the simulation of FIG. 68A.

FIG. 69A illustrates a computer simulation model that performs an exemplary evaluation factor function.

FIG. 69B shows a table summarizing data associated with the simulation of FIG. 69A.

FIG. 69C shows a table summarizing data associated with the simulation of FIG. 69A.

FIG. 70A shows a table summarizing data associated with a simulation of an exemplary evaluation factor algorithm.

FIG. 70B shows a table summarizing data associated with a simulation of the exemplary evaluation factor algorithm of FIG. 70A.

FIG. 71A illustrates a computer simulation model that performs an exemplary evaluation factor function.

FIG. 71B shows a table summarizing data associated with the simulation of FIG. 71A.

FIG. 71C shows a table summarizing data associated with the simulation of FIG. 71A.

FIG. 72A illustrates a computer simulation model that performs an exemplary evaluation factor function.

FIG. 72B shows a table summarizing data associated with a simulation of an exemplary evaluation factor algorithm.

FIG. 72C shows a table summarizing data associated with a simulation of an exemplary evaluation factor algorithm.

FIG. 73A shows a table summarizing data associated with a simulation of an exemplary evaluation factor algorithm.

FIG. 73B shows a table summarizing data associated with a simulation of an exemplary evaluation factor algorithm.

FIG. 74 shows a table summarizing data associated with a simulation of an exemplary evaluation factor algorithm.

Fig. 75A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation average initial temperature in the study of the present disclosure.

Figure 75B shows a binary fit line plot of single freeze isolation probability versus pre-ablation average initial temperature in a study of the present disclosure.

Figure 76A shows a bar graph summarizing the single freeze isolation probability versus the lowest initial pre-ablation temperature in the study of the present disclosure.

Figure 76B shows a binary fit line plot of single freeze isolation probability versus lowest initial temperature before ablation in a study of the present disclosure.

Fig. 77A shows a bar graph summarizing the single freeze isolation probability versus the highest initial pre-ablation temperature in the study of the present disclosure.

Figure 77B shows a binary fit line plot of single freeze isolation probability versus highest initial temperature before ablation in a study of the present disclosure.

Fig. 78A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation initial temperature change in the study of the present disclosure.

Fig. 78B shows a binary fit line plot of single freeze isolation probability versus initial pre-ablation temperature change in a study of the present disclosure.

Fig. 79A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation distributed initial temperature in the study of the present disclosure.

Fig. 79B shows a binary fit line plot of single freeze isolation probability versus pre-ablation distributed initial temperature in a study of the present disclosure.

Fig. 80A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation distributed initial temperature in the study of the present disclosure.

Figure 80B shows a binary fit line plot of single freeze isolation probability versus pre-ablation distributed initial temperature in a study of the present disclosure.

Figure 81A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation distributed initial temperature in the study of the present disclosure.

Figure 81B shows a binary fit line plot of single freeze isolation probability versus pre-ablation distributed initial temperature in a study of the present disclosure.

Fig. 82A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation average initial impedance in studies of the present disclosure.

Figure 82B shows a binary fit line plot of single freeze isolation probability versus pre-ablation mean initial impedance in a study of the present disclosure.

Fig. 83A shows a bar graph summarizing the single freeze isolation probability versus the lowest initial pre-ablation impedance in the study of the present disclosure.

Fig. 83B shows a binary fit line plot of single freeze isolation probability versus lowest initial impedance before ablation in a study of the present disclosure.

Fig. 84A shows a bar graph summarizing the single freeze isolation probability versus the highest initial impedance before ablation in the study of the present disclosure.

Figure 84B shows a binary fit line plot of single freeze isolation probability versus highest initial impedance before ablation in a study of the present disclosure.

Fig. 85A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation initial impedance change in studies of the present disclosure.

Fig. 85B shows a binary fit line plot of single freeze isolation probability versus initial impedance change before ablation in a study of the present disclosure.

Fig. 86A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation initial anterior wall impedance in studies of the present disclosure.

Fig. 86B shows a binary fit line plot of single freeze isolation probability versus initial anterior wall impedance before ablation in a study of the present disclosure.

Fig. 87A shows a bar graph summarizing the single freeze isolation probability versus the lowest initial pre-ablation anterior wall impedance in the study of the present disclosure.

Fig. 87B shows a binary fit line plot of single freeze isolation probability versus lowest initial anterior wall impedance before ablation in a study of the present disclosure.

Fig. 88A shows a bar graph summarizing the single freeze isolation probability versus the highest initial pre-ablation anterior wall impedance in the study of the present disclosure.

Fig. 88B shows a binary fit line plot of single freeze isolation probability versus highest initial anterior wall impedance before ablation in a study of the present disclosure.

Fig. 89A shows a bar graph summarizing the single freeze isolation probability versus the pre-ablation initial anterior wall impedance change in the study of the present disclosure.

Figure 89B shows a binary fit line plot of single freeze isolation probability versus initial anterior wall impedance change before ablation in a study of the present disclosure.

Figure 90A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation average temperature slope in studies of the present disclosure.

Figure 90B shows a binary fit line plot of single freeze isolation probability versus pre-ablation average temperature slope in a study of the present disclosure.

Fig. 91A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation minimum temperature slope in studies of the present disclosure.

Fig. 91B shows a binary fit line plot of single freeze isolation probability versus pre-ablation minimum temperature slope in a study of the present disclosure.

Fig. 92A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation maximum temperature slope in the study of the present disclosure.

Fig. 92B shows a binary fit line plot of single freeze isolation probability versus maximum temperature slope before ablation in a study of the present disclosure.

Fig. 93A shows a bar graph summarizing single freeze isolation probability versus pre-ablation temperature slope change in studies of the present disclosure.

Fig. 93B shows a binary fit line plot of single freeze isolation probability versus pre-ablation temperature slope change in a study of the present disclosure.

Figure 94A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation average temperature rise in studies of the present disclosure.

Figure 94B shows a binary fit line plot of single freeze isolation probability versus pre-ablation average temperature rise in the study of the present disclosure.

Figure 95A shows a bar graph summarizing single freeze isolation probability versus pre-ablation minimum temperature rise in studies of the present disclosure.

Figure 95B shows a binary fit line plot of single freeze isolation probability versus minimum temperature rise before ablation in a study of the present disclosure.

Fig. 96A shows a bar graph summarizing the single freeze isolation probability versus the pre-ablation maximum temperature rise in the study of the present disclosure.

Figure 96B shows a binary fit line plot of single freeze isolation probability versus maximum pre-ablation temperature rise in a study of the present disclosure.

Fig. 97A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation temperature rise change in the study of the present disclosure.

Fig. 97B shows a binary fit line plot of single freeze isolation probability versus pre-ablation temperature rise change in the study of the present disclosure.

Figure 98A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation maximum average temperature in studies of the present disclosure.

Figure 98B shows a binary fit line plot of single freeze isolation probability versus pre-ablation maximum mean temperature in a study of the present disclosure.

Figure 99A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation minimum maximum temperature in studies of the present disclosure.

Figure 99B shows a binary fit line plot of single freeze isolation probability versus pre-ablation lowest maximum temperature in a study of the present disclosure.

Figure 100A shows a bar graph summarizing the single freeze isolation probability versus pre-ablation maximum temperature in the study of the present disclosure.

Figure 100B shows a binary fit line plot of single freeze isolation probability versus pre-ablation maximum temperature in a study of the present disclosure.

Figure 101A shows a bar graph summarizing the single freeze isolation probability versus the maximum pre-ablation temperature change in the study of the present disclosure.

Figure 101B shows a binary fit line plot of single freeze isolation probability versus maximum pre-ablation temperature change in a study of the present disclosure.

Fig. 102A shows a bar graph summarizing single freeze isolation probability versus pre-ablation mean impedance drop in studies of the present disclosure.

Figure 102B shows a binary fit line plot of single freeze isolation probability versus pre-ablation mean impedance drop in a study of the present disclosure.

Fig. 103A shows a bar graph summarizing the single freeze isolation probability versus the pre-ablation lowest value impedance drop in the study of the present disclosure.

Figure 103B shows a binary fit line plot of single freeze isolation probability versus pre-ablation lowest value impedance drop in a study of the present disclosure.

Fig. 104A shows a bar graph summarizing the single freeze isolation probability versus the pre-ablation highest value impedance drop in the study of the present disclosure.

Figure 104B shows a binary fit line plot of single freeze isolation probability versus pre-ablation maximum impedance drop in a study of the present disclosure.

Figure 105A shows a bar graph summarizing single freeze isolation probability versus pre-ablation impedance drop variation in studies of the present disclosure.

Figure 105B shows a binary fit line plot of single freeze isolation probability versus pre-ablation impedance drop change in a study of the present disclosure.

Fig. 106A shows a bar graph summarizing the single freeze isolation probability versus the percentage of the lowest value impedance drop prior to ablation in the study of the present disclosure.

Figure 106B shows a binary fit line plot of single freeze isolation probability versus percentage of lowest value impedance drop prior to ablation in a study of the present disclosure.

Figure 107A shows a bar graph summarizing the single freeze isolation probability versus the pre-ablation percentage change in impedance drop in the study of the present disclosure.

Figure 107B shows a binary fit line plot of single freeze isolation probability versus percent change in pre-ablation impedance drop in a study of the present disclosure.

Fig. 108A shows a bar graph summarizing single freeze isolation probability versus pre-ablation initial impedance deviation from mean in studies of the present disclosure.

Figure 108B shows a binary fit line plot of single freeze isolation probability versus pre-ablation initial impedance deviation from the mean in a study of the present disclosure.

Fig. 109 shows a table summarizing predictors associated with corresponding pearson-related values and binary logistic regression values in studies of the present disclosure.

Fig. 110 shows a table summarizing pre-ablation and post-ablation parameters in a study of the present disclosure.

Figure 111 shows a binary fit line plot of single freeze isolation probability versus pre-ablation lowest anterior impedance in a study of the present disclosure.

Fig. 112 shows a binary fit line plot of single cryo-isolation probability versus pre-ablation impedance change in studies of the present disclosure.

Fig. 113 shows a binary fit line plot of single cryo-isolation probability versus pre-ablation lowest impedance in a study of the present disclosure.

Figure 114 shows a binary fit line plot of single freeze isolation probability versus pre-ablation mean impedance in a study of the present disclosure.

Figure 115 shows a binary fit line plot of single freeze isolation probability versus pre-ablation impedance change in the study of the present disclosure.

Figure 116 shows a binary fit line plot of single freeze isolation probability versus lowest maximum temperature after ablation in a study of the present disclosure.

Figure 117 shows a binary fit line plot of single freeze isolation probability versus minimum impedance drop after ablation in a study of the present disclosure.

Figure 118 shows a binary fit line plot of single freeze isolation probability versus post-ablation mean impedance drop in studies of the present disclosure.

Figure 119 shows a binary fit line plot of single freeze isolation probability versus post-ablation impedance drop change in the study of the present disclosure.

Figure 120A shows a graph summarizing electrode temperature versus time in a study of the present disclosure.

Fig. 120B shows a graph summarizing electrode impedance versus time in a study of the present disclosure.

Fig. 121 shows a table summarizing impedance values and temperature values from single freeze information according to the graphs of fig. 120A to 120B.

Fig. 122 shows a table demonstrating temperature and impedance trends in the electrodes of a balloon catheter in relation to a single freeze versus no isolation comparison for the cases of the study of the present disclosure.

Fig. 123A shows a graph summarizing electrode temperature versus time in a study of the present disclosure.

Fig. 123B shows a graph summarizing electrode impedance versus time in a study of the present disclosure.

Fig. 124 shows a graph summarizing electrode impedance phase versus time in a study of the present disclosure.

Figure 125 depicts a graphical overview of one method or use according to the present disclosure.

FIG. 126 depicts a graphical overview of one method or use according to the present disclosure.

FIG. 127 illustrates an exemplary flow diagram of a subroutine for determining a probability of success.

Fig. 128 shows an exemplary graphical display representing characteristics and identification of electrodes energized during an exemplary ablation.

Detailed Description

Although exemplary embodiments of the disclosed technology are explained in detail herein, it should be understood that other embodiments are also intended to be within the scope of the claimed invention. Accordingly, it is not intended to limit the scope of the disclosed technology to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The disclosed technology is capable of other embodiments and of being practiced or of being carried out in various ways.

It should also be noted that, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. By "comprising" or "containing" or "including" is meant that at least the named compound, element, particle, or method or use step is present in the composition or article or method or use, but does not preclude the presence of other compounds, materials, particles, methods or use steps, even if other such compounds, materials, particles, methods or use steps have the same function as those named.

As used herein, the term "about" or "approximately" for any numerical value or range of numbers indicates a suitable dimensional tolerance that allows a portion or collection of multiple components to perform its intended purpose as described herein. More specifically, "about" or "approximately" may refer to a range of values of ± 20% of the recited value, e.g., "about 90%" may refer to a range of values from 71% to 99%.

In addition, as used herein, the terms "patient," "host," "user," and "subject" refer to any human or animal subject and are not intended to limit the system or method or use to human use, although use of the subject invention in a human patient represents a preferred embodiment.

In describing exemplary embodiments, terminology will be resorted to for the sake of clarity. It is intended that each term adopts its broadest meaning as understood by those skilled in the art and includes all technical equivalents which operate in a similar manner to accomplish a similar purpose. It will also be understood that reference to one or more steps of a method or use does not preclude the presence of additional method or use steps or intermediate method or use steps between those steps expressly identified. The steps of a method or use may be performed in an order different than the order described herein without departing from the scope of the disclosed technology. Similarly, it should also be understood that reference to one or more components in an apparatus or system does not preclude the presence of additional components or intervening components between those expressly identified components.

As discussed herein, the vasculature of a "subject" or "patient" may be that of a human or any animal. It is to be understood that the animal can be of any of a variety of suitable types, including but not limited to mammals, veterinary animals, livestock animals, or companion animals, and the like. For example, the animal can be an experimental animal (e.g., rat, dog, pig, monkey, etc.) specifically selected to have certain characteristics similar to those of a human. It will be appreciated that the subject may be, for example, any suitable human patient.

As discussed herein, an "operator" may include a doctor, surgeon, or any other individual or delivery meter device associated with delivering a multi-electrode radio frequency balloon catheter for treating drug refractory atrial fibrillation to a subject.

As used herein, "NIHSS score" refers to the american national institute of health stroke scale or NIH stroke scale (NIHSS), and is a tool used by healthcare providers to objectively quantify the damage caused by stroke. NIHSS consists of 11 items, each item scoring a particular capability between 0 and 4. For each item, a score of 0 generally indicates that the particular capability is functioning properly, while a higher score indicates a degree of impairment. The individual scores for each item are summed to calculate the total NIHSS score for the patient. The maximum possible score was 42 and the minimum score was 0.

As discussed herein, "mRS" refers to the modified Rankin scale (mRS), which is a common scale used to measure the degree of disability or dependence in the daily activities of persons suffering from stroke or other neurological disabilities. The mRS scale ranges from 0-6, from asymptomatic health to death. An mRS score of 0 indicates no symptoms were observed. An mRS score of 1 is understood as meaning that no significant disability is observed and that the patient is able to perform all routine activities despite certain symptoms. An mRS score of 2 is considered a mild disability, and the patient is able to take care of his business without assistance, but is unable to perform all previous activities. An mRS score of 3 is understood to be moderately disabled, so the patient may need some help, but can walk without assistance. An mRS score of 4 is understood to mean moderate severe disability, a patient is unable to meet his physical needs without assistance, or is unable to walk unassisted. An mRS score of 5 is understood as a severe disability, patient need for constant care and care, bedridden, incontinence. An mRS score of 6 is understood as the patient having died.

As discussed herein, the term "safety" when referring to a device, associated delivery system, or treatment method or use for ablating cardiac tissue refers to a relatively low severity of adverse events, wherein adverse events include adverse bleeding events, infusion reactions, or hypersensitivity reactions. Adverse bleeding events can be a primary safety endpoint and include, for example, major bleeding, minor bleeding, and individual components of any bleeding event composite endpoint.

As used herein, unless otherwise indicated, the term "clinically effective" (used alone or to modify the term "effective") can mean that a clinical trial has proven effective, wherein the clinical trial has met the approval standards of the U.S. food and drug administration, EMEA, or corresponding national regulatory agency. For example, the clinical study may be a sample size adequate, randomized, double-blind control study for clinically demonstrating the efficacy of the cardiac ablation devices and related systems of the present disclosure. Most preferably, the effect of the device is clinically demonstrated for all targeted pulmonary veins, e.g., achieving clinically effective outcomes for the patient (e.g., mRS less than or equal to 2) and/or pulmonary vein isolation for those diseased veins.

As discussed herein, the term "computed tomography" or CT refers to one or more scans that utilize a combination of computer processing of many X-ray measurements taken from different angles to produce a cross-sectional (tomographic) image (virtual "slice") of a particular region of a scanned object, allowing a user to see inside the object without cutting. Such CT scans of the present disclosure may 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).

The present disclosure relates to systems, methods or uses and devices for ablating cardiac tissue to treat cardiac arrhythmias. Ablation energy is typically provided to the cardiac tissue by a tip portion that can deliver ablation energy along the tissue to be ablated. Some of these catheters apply ablation energy from various electrode three-dimensional structures. Fluoroscopy may be used to visualize ablation protocols incorporating such catheters.

The use of cardiac tissue ablation to correct cardiac malfunction is a well-known procedure. Typically, for successful ablation, cardiac electrode potentials need to be measured at various locations of the myocardium. Furthermore, temperature measurements during ablation provide data enabling the efficacy of the ablation to be measured. Typically, for ablation protocols, electrode potentials and temperatures are measured before, during, and after the actual ablation.

Previous solutions have used two or more separate instructions (e.g., one for measuring electrode potential and temperature, and another for ablation), embodiments disclosed herein facilitate both measurements, and in addition enable ablation with radiofrequency electromagnetic energy using a single catheter. The catheter has a lumen, and the balloon is deployed through the catheter lumen (the balloon travels through the lumen in a collapsed, uninflated configuration, and the balloon inflates as it exits the lumen). The balloon has an outer wall or membrane and has a distal end and a proximal end defining a longitudinal axis of the extended lumen.

For example, fig. 1 depicts an exemplary meter apparatus including a device 12 according to one exemplary embodiment. The procedure is performed by the operator 14 and it is assumed that the procedure in the following description includes ablating a portion of the myocardium 16 of the heart of a human patient 18. However, it should be understood that the embodiments disclosed herein are not applicable to this particular procedure only, but may also include essentially any procedure directed to biological tissue or non-biological material.

To perform ablation, the operator 14 inserts the probe 20 into a sheath 21 that has been previously positioned in the lumen of the patient. The sheath 21 is positioned such that the distal end 22 of the probe 20 enters the patient's heart. A multi-electrode radio frequency balloon catheter 24 (e.g., a balloon catheter), described in more detail below, is deployed through the lumen 23 of the probe 20 and exits from the distal end of the probe 20. Catheter 24 may be a multi-electrode radio frequency balloon catheter for cardiac electrophysiology ablation of the atrial pulmonary veins, and when used with a multi-channel radio frequency generator, for treating drug-refractory relapsing symptomatic PAF, as discussed in more detail below. Conduit 24 and changes or updates to conduit 24 can be understood to include features described more clearly in appendix 1, which is incorporated by reference in its entirety into the priority U.S. provisional applications including U.S. patent nos. 9,907,610, 9,956,035; U.S. patent publications 2015/0272667, 2016/0175041, 2017/0311893, 2017/0311829, 2017/0312022a1, 2018/0280080a1(15/476,191), 2018/0161093, 2019/0183567(15/847,661), 2019/0175262, 2019/0060622(15/684,434), 2019/0217065(15/870,375), 2019/0143079(15/815,394), 2017/0347896, 2016/0175041, each of which is incorporated by reference in its entirety as if set forth verbatim herein. It is noted that such a catheter 24 may also be introduced through the femoral artery, the wrist artery (radial access) or directly through the carotid artery. Although radial and carotid approaches avoid the aortic arch, other disadvantages exist. However, all three methods are considered to be known to the person skilled in the art.

Functionally, the catheter 24 attempts to achieve isolation of the pulmonary veins in the subject LA to eliminate AF symptoms. Catheter 24 simultaneously ablates from multiple independently controlled irrigated electrodes. The amount of power delivered to each electrode is independently controlled to improve safety and lesion quality.

One radio frequency generator intended for use in the present disclosure may be used in cardiac ablation applications to generate radio frequency energy for delivery to a site in the heart via a compatible radio frequency ablation catheter. The generator is capable of independently controlling the delivery of radiofrequency energy to the electrodes simultaneously. The generator may include functionality for controlling ablation parameters at an ablation electrode of the catheter. Ablation parameters, such as power, impedance, ablation duration and temperature, are recorded and may be exported to the USB device at the end of the procedure. The generator is typically configured to measure and display a magnitude of a complex impedance (Z) that is at least intended to represent an impedance of patient tissue proximate the ablation electrode. For impedance measurements, the generator uses each of a plurality of electrodes (i.e., one lead wire through the catheter to each ablation electrode) and one radio frequency independent/distributed return electrode (i.e., one lead wire from the radio frequency independent return electrode back to the generator) -this is a two terminal configuration for the measurement of each electrode. With this arrangement, the generator generates a small current between each electrode and the indifferent electrode, and measures the voltage resulting from the current to calculate the impedance of each electrode. As configured in this system, the impedance of tissue in contact with each of the ten electrodes may be detected and analyzed by the processor 46 to provide indicators and guidance to the operator during or after the procedure.

As shown in fig. 1-2, the device 12 is controlled by a system processor 46, which is located in the device's operating console 15. Console 15 includes controls 49 used by practitioner 14 to communicate with the processor. During the procedure, the processor 46 generally tracks the position and orientation of the distal end 22 of the probe 20 using any method or use known in the art. For example, processor 46 may use a magnetic tracking method or use in which magnetic transmitters 25X, 25Y, and 25Z external to patient 18 generate signals in coils positioned in the distal end of probe 20.

The system (available from Biosense Webster, Inc. (Irvine, California)) uses such tracking methods or uses.

To operate the device 12, the processor 46 communicates with a memory 50 having a plurality of modules used by the processor to operate the device. Accordingly, memory 50 includes a temperature module 52, an ablation module 54, and an Electrocardiogram (ECG) module 56, the functions of which are described below. Memory 50 typically includes other modules, such as a force module for measuring force on distal end 22, a tracking module for operating a tracking method or use used by processor 46, and a perfusion module that allows the processor to control perfusion provided for distal end 22.

Although other modules are not shown in fig. 1, they are actually intended to be within the scope of the claimed invention and may include hardware elements as well as software elements. For example, module 54 may include a radio frequency generator having at least one output or output channel (e.g., ten outputs or ten output channels). Each of these outputs may be individually and selectively enabled or disabled by a switch. That is, each switch may be disposed between the signal generator and the corresponding output. Thus, a generator with ten outputs will include ten switches. These outputs may each be individually coupled to electrodes on the ablation catheter, such as ten electrodes 33 on balloon 80, as described in further detail below. The electrodes 33 may be perfused flexible gold-plated electrodes bonded to an ablation catheter for delivering radio frequency energy to tissue and sensing temperature at each electrode in a monopolar fashion. The electrodes 33 may be circularly oriented to achieve good circumferential contact with the pulmonary vein ostium. Catheter 24 may simultaneously ablate cardiac tissue from independently controlled electrodes when paired with a multi-channel radio frequency generator, and the amount of power delivered to each electrode is independently controlled.

Such electrical connection may be achieved by establishing an electrical path between each output and each electrode. For example, each output may be connected to a corresponding electrode by one or more wires or suitable electrical connectors. Thus, in some embodiments, the electrical path may include at least one wire. In some embodiments, the electrical path may further include an electrical connector and at least a second wire. Thus, electrode 33 may be selectively activated and deactivated with a switch to receive radio frequency energy independently of each of the other electrodes.

Fig. 2 illustrates a catheter 24 having a usable length of about 110cm (although other dimensions are intended to be within the scope of the claimed invention, as needed or desired). The conduit 24 may have three main sections: a handle 42, a shaft portion 82, and a distal tip 22. Shaft 82 may measure 10.5F (french) and has a maximum outer diameter of 13.5F around balloon 80 when it is in its fully collapsed state. Catheter 24 may have a high torque shaft 82, and a deflectable end section that is unidirectional braided. This shaft allows the plane of the curved tip to rotate with balloon 80 to facilitate precise positioning of catheter tip 22 to the desired site (pulmonary vein ostium). The compliance of balloon 80 allows its flexible surface electrodes 33 to conform to the anatomy when pressed against tissue.

The handle section 42 may incorporate a deflecting thumb knob that allows for unidirectional deflection, a balloon advancement mechanism, and a luer fitting for balloon inflation and irrigation. Additional luer fittings may be included, located proximal to the ejector, and used as an inlet for a guidewire and an inlet for distal perfusion and/or contrast injection. Catheter 24 may be used with an infusion pump to control infusion of the balloon. Heparinized saline may be delivered through the luer fitting of the handle 42.

Fig. 3 is a schematic perspective view of an exemplary multi-electrode radio frequency balloon catheter 24 in an expandable configuration in the form of a balloon in its expanded configuration, according to one embodiment used in this study. In one disclosed embodiment, where the multi-electrode radio frequency balloon catheter 24 is used to ablate the ostium 11 of a lumen, such as pulmonary vein 13, the multi-electrode radio frequency balloon catheter 24 is supported by a tubular shaft 70 having a proximal shaft portion 82 and a distal shaft end 88. The shaft 70 includes a hollow center tube 74 that allows a catheter to pass therethrough and past the distal shaft end 88. The catheter may be a lasso catheter 72 (as illustrated) or a diagnostic catheter (i.e., for recording ECG signals propagating through heart tissue). It is also contemplated that the catheter may have a relatively small diameter (e.g., about 3mm) through which a similarly small diameter catheter may be used, such as a focal linear catheter or the like. The lasso catheter 72 may be inserted into the pulmonary vein to properly position the multi-electrode radio frequency balloon catheter 24 relative to the pulmonary vein ostium prior to ablation of the pulmonary vein ostium. The distal lasso portion of the catheter 72 is typically formed of a shape memory retention material such as nitinol. It should be understood that the multi-electrode radio frequency balloon catheter 24 may also be used with a linear or focal catheter 99 (shown in phantom in fig. 3) in the pulmonary vein or other portion of the heart. Any catheter used with the multi-electrode radio frequency balloon catheter 24 can have a variety of features and functions including, for example, pressure sensing, ablation, diagnosis (e.g., steering and pacing).

The balloon 80 of the multi-electrode radiofrequency balloon catheter 24 can be of a biocompatible material (e.g., made of a material such as polyethylene terephthalate (PET), polyurethane, or

Plastic) or membrane 26. The shaft 70 and the distal shaft end 88 define the longitudinal axis 78 of the balloon 80. The balloon 80 is deployed in a collapsed configuration through the lumen 23 of the probe 20 and may expand after exiting from the distal end 22. The membrane 26 of the balloon 80 is formed with perfusion apertures or holes 27 through which fluid (e.g., saline) can be expelled from the interior of the balloon 80 to the exterior of the balloon to cool the tissue ablation site at the ostium. It should be understood that the fluid can exit the balloon 80 at any desired flow rate or pressure, including the rate at which fluid seeps from the balloon 80.

Another embodiment of a catheter, referred to herein as a probe 24', may be utilized. Fig. 4A illustrates an exploded perspective view of an electrophysiology probe 24' including a tubular member 302 that extends along a longitudinal axis L-L from a first (proximal) end 302b to a second (or distal) end 302 a. The first inflatable membrane 204 is attached to the tubular member 302 near the distal end 302 b. The membrane 204 has an outer surface 204a and an inner surface 204b disposed about the longitudinal axis L-L. The outer surface 204a is exposed to the ambient environment, while the inner surface 204b is exposed to the interior volume of the balloon defined by the membrane 204. The first inflatable membrane 204 has a first inflatable distal membrane portion 208 coupled to the second end 302a of the tubular member 302 and a second inflatable distal membrane portion 206 spaced apart from the first inflatable distal membrane portion 208 along the longitudinal axis L-L.

Note that the first inflatable membrane 204 is configured to be inflated from a compressed shape (a generally tubular configuration) to a balloon (or generally spherical) shaped member. A plurality of electrodes 210a, 210b, 210c, 210d, 210e, 210f, 210g, 210h, 210i, and 210j (which may be referred to individually or collectively as "electrodes 210") are disposed on the outer surface 204a of the first inflatable membrane 204. The electrodes 210 are arranged such that they radiate from a generally common center or center of gravity base 212 located near the second expandable distal membrane portion 208 distal of the tubular member 302. The electrodes 210a-210j may have one or more wires, i.e., bifilar wires 214a-214j, connected to each of the plurality of electrodes 210a-210j via connection junctions 216a-216j, respectively. Each of the leads 214a-214j (which may be a singular form of a "lead," or a plurality of "leads" will be collectively referred to as "leads 214") is connected to a connection point on the "underside" surface of the electrode 210. The underside surface of each electrode 210 is the electrode surface that is not exposed to the ambient environment and is typically bonded to the outer surface 204a of the membrane 204. Since the connection point 216 (typically a solder joint) is generally located at the center of the electrodes, the wires are covered by the underside surface of each electrode. However, as each lead or twin lead 214a-214j extends toward the tubular member 302, the electrode surface or substrate (to which the electrode is bonded) becomes smaller, thereby exposing the lead or twin lead 214a-214 j.

As can be seen in fig. 4B, when a set of wires 214a-214j are mounted on the film 204, each wire 214 is configured to extend from the tubular member 302 to a respective electrode 210 such that each wire follows the topography of the outer surface 204a of the film 204. As each lead 214 exits the underside surface of each electrode or the underside surface of the substrate 213 during extension of the lead 214 toward the tubular member 302, the lead 214 becomes exposed to the surrounding environment (e.g., biological tissue or blood) (fig. 5). Since each of the wires 214 may be used to conduct or transmit electrical energy or signals, it may be detrimental to expose the wires 214 to the surrounding biological tissue environment. Thus, we have designed a second inflatable membrane 200 that encapsulates one or more conductive wires (214a-214j) between the second inflatable membrane 200 and the first inflatable membrane 204 such that the conductive wires 214a-214j are constrained between the first inflatable membrane and the second inflatable membrane (fig. 7). This configuration eliminates exposure of the leads to the ambient environment, but still allows the electrode/thermocouple to be exposed to biological tissue, allowing the electrode and thermocouple to function for their intended purposes. Further, when the wires 214 are constrained or captured between the first and second membranes, there is little likelihood that the wires will become tangled or incorrectly connected to the wrong electrode or thermocouple during assembly. In the preferred embodiment, each of the bifilar wires is coupled to a temperature sensor in the form of a thermocouple 216 disposed on or near each electrode 210.

It is noted that tubular member 302 defines a first internal passage in the form of lumen 302c, shown here as a dashed line in fig. 5, that extends from first end 302a to second end 302b of tubular member 302 such that one or more wires are disposed in first lumen 302 c. To allow other instruments (e.g., a guidewire, optical sensor, etc.) to be delivered through balloon 204 (and outside of distal-most portion 209 of the balloon), tubular member 302 may be provided with a second lumen 302d that extends through membrane portions 206 and 208 to allow another instrument to pass through second lumen 302 d. In addition to this, the tubular member 302 may be provided with another internal passage in the form of a third lumen 302 e. Perfusion fluid may be disposed in either of the second lumen 302d or the third lumen 302e such that the perfusion fluid flows into the interior volume of the membrane 204 through openings or pores 220 provided to the exterior of the membrane 204 through the inner and outer membrane surfaces 204b and 204a to the surrounding environment (e.g., biological tissue or organ). Each electrode may have four perfusion openings formed on the electrode such that the electrode perfusion openings are aligned with the apertures 220 of the membrane. In this preferred embodiment, lumens 302c, 302d and 302e are configured or extruded as concentric channels in the form of tube 302e within tube 302d, tube 302d within tube 302c, and having an outer tubular member 302. Tubular member 302 may be a suitable biocompatible polymer known to those skilled in the art.

Referring to fig. 4B, a plurality of electrodes 210a-210j extend equiangularly about the longitudinal axis L-L from the base center of gravity 212 from the first expandable distal membrane portion 208 toward the second expandable distal membrane portion 206 such that the second expandable membrane 200 encloses a portion of each of the electrodes (210a-210j) proximate the second expandable membrane portion 206. The second inflatable membrane 200 has a boundary 202 (fig. 4A) that extends over a proximal portion (i.e., fish head 115) of the outer surface of the electrode 210 (fig. 4B) while allowing the electrode fishbone pattern 210 to be exposed to the surrounding environment.

That is, each of the plurality of electrodes 210a-210j defines a fishbone pattern that is not covered by the second inflatable membrane 200 to allow exposure of the fishbone electrode to the surrounding environment. Each electrode (210a-210j) is coupled to the outer surface of the first inflatable membrane 204 via a substrate 213 that is itself connected or bonded to the outer surface 204a of the first inflatable membrane 204. The electrodes 210a-210j may have a portion of their perimeter bonded directly to the membrane 204. A suitable seal 211 may be formed such that the seal 211 extends along the outer perimeter of the base 213 of each electrode (210a-210 j). In a preferred embodiment, the seal 211 can be provided in the form of a polyurethane seal.

Referring to fig. 5, radiopaque markers 230 are defined by the proximal fish head portion of each electrode such that there may be a respective radiopaque marker 230a, 230b, 230c, 230d, 230e, 230f, 230g, 230h, 230i, and 230j for the corresponding electrode 210a-210 j. To ensure that the position of each electrode can be determined with X-rays inside the body organ, each electrode 210 can have a radiopaque marker (230a-230j), with each marker having a different configuration than the other radiopaque markers on the other electrodes.

Referring back to fig. 4A, the third inflatable membrane 300 may be disposed proximate the first inflatable distal membrane portion 208 such that the third inflatable membrane 300 encircles an outer surface portion of the first inflatable membrane 204 about the longitudinal axis L-L proximate the distal portion 209 of the membrane 204. The third inflatable membrane encloses a portion of the substrate 213 (fig. 5) for each of the plurality of electrodes near the distal portion 209 of the membrane 204. Preferably, the third inflatable membrane 300 allows the substrate 213 of each electrode (210a-210j) to be encapsulated as the substrate 213 converges to the center of gravity 212 near the distal portion 209 of the membrane 204. A retaining ring 209 is disposed about the third inflatable membrane 300 (disposed near the distal portion 208 of the membrane 204) to retain the third inflatable membrane 300 and the substrate 213 to the first inflatable membrane 204. The third inflatable membrane 300 may be bonded to the first inflatable membrane 204, thereby trapping the substrate 213 between the two membranes (204 and 300).

Referring to FIG. 6A, an enlarged side view of a portion of the septum of FIG. 4A is shown. Fig. 6B shows the uncovered lateral or circumferential surface area. In particular, the surface area of the membrane 204 exposed by (i.e., not covered by) the second inflatable membrane 200 and the third inflatable membrane has a circumferential surface area L defined between a virtual slice S1 orthogonal to the axis L-L (defined by the intersection of the third inflatable membrane 300 with the first inflatable membrane 204) and a virtual slice S2 orthogonal to the longitudinal axis L-L, whereby the slice S2 is defined by the intersection of the second inflatable membrane 200 and the first inflatable membrane 204. For clarity, it can be seen in fig. 6B that if the first inflatable membrane 204 approximates a sphere (when the membrane 204 is inflated to its service characteristics), the circumferential surface area L can be determined once the parameters of the spherical body are known. In the preferred embodiment shown in fig. 7, the first inflatable membrane 204 includes a circumferential surface area L (fig. 5 and 6B) that is approximately 52% of the total surface area of the first inflatable membrane 204. That is, the circumferential surface area L is an exposed surface area of the first inflatable membrane 204 (without any electrodes and substrates) or an outer circumferential area of the first inflatable membrane 204 that is also not covered by the second and third inflatable membranes 200, 300. Additionally, it is noted that each base 213 of each electrode 210 includes a base surface area that is approximately 8% of the exposed outer circumferential surface area L of the first inflatable membrane 204. In a preferred embodiment, the second inflatable membrane 200 and the third inflatable membrane 300 cover approximately half of the exterior surface area of the first inflatable membrane 204.

In a preferred embodiment, the first inflatable membrane comprises a generally spherical member having a diameter with reference to the longitudinal axis L-L of about 30 millimeters, and the second and third inflatable membranes each comprise a hemispherical member, wherein the respective major diameter of each hemispherical member is less than 30 mm. In a preferred embodiment, the total surface area of membrane 204 is about 4500 square millimeters and the circumferential surface area L is about 2400 square millimeters, and each flexible substrate 213 is about 200 square millimeters when membrane 204 is in its fully expanded (i.e., designed) configuration, as exemplarily shown in fig. 7.

The balloon 204 of the diagnostic/therapeutic catheter is of a biocompatible material (e.g., made of a material such as polyethylene terephthalate (PET), polyurethane, or

Plastic ofMaterial formed) outer wall or membrane 204 a. The tubular shaft 302 and the distal shaft end 302a define a longitudinal axis L-L of the balloon 204. Balloon 204 was manufactured as described in commonly owned U.S. patent application serial No. 15/939,154 (attorney docket No. 400528-]) Deployed (via lumen 23 of probe 20 in the present prior application, which is incorporated herein by reference). The membrane 204a of the balloon 204 is formed with perfusion apertures or holes 220 (shown in fig. 5) through which fluid (e.g., saline) may be expelled from the interior of the balloon 204 to the exterior of the balloon to cool the tissue ablation site at the port.

As described earlier with respect to fig. 4B, the membrane 24 supports and carries the electrodes and temperature sensing members configured as a combination of the multi-layer flex circuit electrode assemblies 210a-210 j. The "flex circuit electrode assemblies" 210a-210j may have many different geometric configurations than those shown here. In the illustrated embodiment, the flexible circuit electrode assemblies 210a-210j have a plurality of radial bases or strips 213a-213j, as best shown in FIG. 2. The bases 213a-213j are evenly distributed around the distal end 209 and the balloon 204. Each base 213a-213j has a wider proximal portion that tapers to a narrower distal portion with reference to the longitudinal axis.

For simplicity, the flex circuit electrode assembly 210 is described with respect to only one of its substrates 213 as shown in fig. 5, but it should be understood that the following description may apply to each substrate 213 of the assembly 210. The flexible circuit electrode assembly 210 includes a sheet-form base material 213 having flexibility and elasticity constructed of a suitable biocompatible material (e.g., polyimide). In some embodiments, the sheet-form base material 213 has a higher heat resistance (or higher melting temperature) than the balloon membrane 204. In some embodiments, the base material 213 is constructed from a thermoset material having a decomposition temperature that is about 24 degrees celsius or greater than the melting temperature of the balloon membrane 204.

The base material 213 is formed with one or more perfusion apertures or holes (not labeled) that are aligned with the perfusion holes 220 of the balloon member 204 so that fluid passing through the perfusion holes 220 (not labeled) can be delivered to the ablation site on the ostium.

The base material 213 has a first or outer surface facing away from the balloon membrane 204 and a second or inner surface facing the balloon membrane 204. On its outer surface, a base material 213 supports and carries the contact electrode 210. The configuration or trace of the contact electrode 210 may be similar to a "fishbone," but it should be noted that the invention is not limited to this configuration. The fingers of the contact electrode 210 advantageously increase the circumferential or equatorial contact surface of the contact electrode 210 with the ostium as compared to a regional or "patch" ablation electrode, while the interstitial regions between adjacent fingers advantageously allow the balloon 204 to collapse inwardly or expand radially as needed at a location along its equator. In the illustrated embodiment, the fingers have different lengths, some being longer and others being shorter. For example, the plurality of fingers includes a distal finger, a proximal finger, and a finger therebetween, wherein each finger therebetween has a shorter adjacent finger. For example, each finger has a different length than its immediately adjacent distal or proximal neighbor, such that the length of each finger generally follows the tapered configuration of each base 213. In the illustrated embodiment, 22 fingers extend through the elongate portion (beyond each lateral side thereof). In some embodiments, contact electrode 210 comprises gold with a seed layer between the gold and film 204. The seed layer may comprise titanium, tungsten, palladium, silver, or combinations thereof.

As shown in fig. 8, the flexible electrode may in variations have its radiopaque markings identified as 231a, 231b, 231c, etc. to help identify the electrode being energized. The indicia 231a-231j have various serpentine configurations (as compared to fig. 7) to allow for increased flexibility due to the presence of the second film 200, which tends to reduce the flexibility of the device in the vicinity of the indicia 231a-231 j.

Fig. 9 is a side view of the distal end of the catheter of fig. 2 deployed in the area of the pulmonary vein and pulmonary vein ostia. Fig. 10 is a top plan view of an exemplary diagnostic catheter of the present disclosure. Fig. 11 is a detailed view of the distal assembly of the diagnostic catheter of fig. 5.

The membrane 26 supports and carries the combined electrodes and temperature sensing components constructed as a multi-layer flex circuit electrode assembly 84. The "flex circuit electrode assembly" 84 can have many different geometric configurations. In the illustrated embodiment, the flexible circuit electrode assembly 84 has a plurality of radiating substrates or strips 30. One or more electrodes 33 on each substrate are in galvanic contact with the port 11 during the ablation procedure, during which time current flows from the electrodes 33 to the port 11, as shown in fig. 4.

The circuit containing the electrodes 33 may be made of a polyimide substrate (e.g., about 0.001 inch thick) with a gold layer on the top (outer surface) and a gold-plated copper layer on the back side (between the circuit and the balloon 80) that is extremely flexible and resilient. To deliver current to the electrodes 33, a bifilar lead may be connected to each electrode 33, routed through the catheter 24, and terminated in a connector in the handle 42. The double-strand wire can be made of a copper wire and a constantan wire. Copper wires may be used for radio frequency delivery. To fit catheter 24 into the sheath, it is necessary to first collapse balloon 80 with its flexible electrodes 33 to a smaller diameter by moving the distal end of balloon 80 forward a certain distance to provide the elongation necessary to reduce the Outer Diameter (OD) of the balloon.

One example of a diagnostic catheter 110 for use in the present disclosure is shown in fig. 10-11 and includes a lasso-type structure to facilitate manipulation and positioning in the heart. Catheter 110 may be understood to include features described more clearly in appendix 2, which is incorporated by reference in its entirety into U.S. provisional applications claiming priority hereto, including U.S. provisional patent application serial No. 62/769,424 (filed 11/19/2019), 62/692,439 (filed 6/29/2018); U.S. Pat. nos. 5,718,241, 6,198,974, 6,484,118, 6,987,995, 7,142,903, 7,274,957, 7,377,906, 7,591,799, 7,593,760, 7,720,517, 7,853,302, 8,000,765, 8,021,327, 8,275,440, and 8,348,888, each of which is incorporated by reference in its entirety as if set forth verbatim herein. Such catheters 110 may be used to create curved, circular, looped, or otherwise closed ablation paths, as well as to sense electrical activity along curved, circular, looped, or closed patterns for electrical potential and anatomical mapping.

Thus, catheter 110 may perform electrophysiological recording and stimulation of the atrial region of the heart, and may be used in conjunction with catheter 24 and other ancillary equipment. The distal end of catheter 110 may be a circular spine with ring electrodes positioned circularly and used for stimulation and recording within the atrium. The annular distal end can have a variety of diameters (15mm, 20mm and 25mm) to achieve optimal contact in a variable sized pulmonary vein. In some examples, the collar tip may be a circular ridge with ten electrodes bonded to its surface, a straight distal tip section, and a hypotube shaft. These ten electrodes may be used for stimulation and recording within the atrium of the heart and are circularly oriented on the collar to achieve proper circumferential contact with the inside of the pulmonary veins. The nominal electrode spacing may comprise 4.5mm for a 15mm collar, 6mm for a 20mm collar and 8mm for a 25mm collar.

A catheter 110 in accordance with disclosed examples may include an elongated body that may include an insertion shaft or catheter body 112 having a longitudinal axis, and an intermediate section 114 distal to the catheter body that may be deflected off-axis, either uni-or bi-directionally, from the catheter body longitudinal axis. Extending from the elongate body 112 or the intermediate section 114 is a resilient three-dimensional distal assembly 117 having a ring electrode 119 disposed along a non-linear or curved distal portion. The helical form is oriented obliquely with respect to a longitudinal axis 125 of the conduit 110 extending from the intermediate section 114. In this respect, the term "obliquely" means that the plane P which best fits the helical form in space is angled with respect to the longitudinal axis 125. The angle θ between plane P and axis 125 is in the range of between about 45 degrees to 105 degrees, preferably between about 75 degrees to 105 degrees, and more preferably about 90 degrees. In addition, the helical form 122 of the distal assembly 117 spirals or subtends in a predetermined manner.

The distal assembly 117 may have a proximal collar 117P carrying the electrodes, and a soft "pigtail" structure comprising a distal collar 117D and a distal straight end section 117E, wherein the distal collar 117D and the distal straight end section 117E have a greater elasticity than the elasticity of the proximal collar 117P carrying the electrodes. The pitch of the helical shape 122 of the distal assembly 117 is selected to provide gentle pressure to ensure that all of the ring electrodes 119 are in contact with the tissue. It will be appreciated that the tapering of the helical shape 122 ensures that the smaller distal collar 117D can fit into the tubular region or pulmonary vein, which ensures placement accuracy of the larger proximal collar 117P and the ring electrode 119 carried thereon at the ostium 111 of the tubular region 113 (e.g., pulmonary vein). The greater flexibility of the distal collar 117D and distal straight end section 117E provides an atraumatic leading element that guides the distal assembly 117 into a tubular region or pulmonary vein and ensures placement accuracy of the distal assembly.

The catheter 110 enters the body of the patient through an introducer sheath that has been inserted into a body cavity, such as a heart chamber. Due to the flexible construction of the distal assembly 117, the helical shape 122 tends to straighten out for insertion into the guide sheath. When exposed and unconstrained, the distal assembly 117 re-assumes the helical shape 122 that is manipulated to frontally engage the tissue surface, with some or all of the ring electrodes 119 on the proximal collar 117P simultaneously contacting the tissue surface.

Fig. 12 is a schematic cross-sectional view of the heart 226 showing the catheter 110 inserted into the heart. To insert the catheter 110, the user first passes the introducer sheath 240 percutaneously through the vascular system and into the right atrium 244 of the heart via the ascending vena cava 242. The sheath penetrates the atrial septum 248, typically via the fossa ovalis, into the left atrium 246. Alternatively, other access paths may be used. The catheter 110 is then inserted through the guide sheath until the distal assembly 117 of the catheter 110 extends past the distal end of the guide sheath 240 into the left atrium 246.

Continuing with the procedure, the operator aligns the longitudinal axis of the introducer sheath 240 (and catheter 110) within the left atrium 246 with the axis of one of the pulmonary veins. Alignment may be performed under fluoroscopy or other visualization means. The user advances the catheter 110 distally toward the pulmonary vein so that the soft distal end 117E enters the pulmonary vein first and then the soft distal collar 117D, both of which guide the positioning and placement of the electrode-carrying proximal collar 117P onto the ostium. The user may apply a force F in the axial direction to press the proximal collar 117P onto the ostium to ensure contact between the ring electrode 119 and the tissue.

The operator can rotate the catheter 110 about its axis within the introducer sheath 240 such that the proximal collar 117P follows an annular path around the inner circumference of the vein. At the same time, the user may actuate the radio frequency generator to ablate tissue in contact with the AR electrode along the path. At the same time, recording of impedance and/or pulmonary vein potential may be performed using IR electrodes and/or RR electrodes. After completing the procedure around one pulmonary vein, the user may displace the sheath 240 and catheter 110 and repeat the procedure around one or more other pulmonary veins.

Overview of the study

The present disclosure may be more clearly understood by corresponding studies discussed in more detail below with respect to the treatment of PAF. Fig. 13 provides, inter alia, a schematic overview of the subject research protocol of the present disclosure, as appendix 3 and appendix 4, each of which is incorporated by reference in its entirety as if set forth verbatim herein. The purpose of this study is to demonstrate that the use of catheter 24 in conjunction with catheter 110 to isolate the atrial pulmonary vein is clinically safe and clinically effective in treating subjects with drug refractory, symptomatic, and paroxysmal atrial fibrillation, as graphically depicted in fig. 3.

The study is a prospective, multi-center, single-arm clinical evaluation using catheter 24 and catheter 110. The sample size used for this study was determined primarily by the safety endpoint. An adaptive bayesian design can be used to determine the sample size based only on the security endpoint. Sample size selection period analysis may be performed when 80, 130, 180, and 230 evaluable subjects are enrolled in the primary study (e.g., the mITT population). The safety results at 30 days will be used as a representative value of the primary safety endpoint at each period of analysis. The final safety analysis was a complete follow-up in the main study for the primary safety endpoints of all evaluable patients. The predicted success probability is used to determine whether the sample size at each time period of analysis is sufficient or whether trial enrollment will continue. A sample size simulation was performed using performance targets of 15% and 80%, respectively, to obtain a ratio of safety endpoint and effectiveness endpoint.

At each session analysis, available data from all evaluable subjects in the mITT population is used to estimate the predicted probability of success, assuming an uninformative uniform prior distribution for the primary safety ratio. Enrollment is stopped if the predicted probability of test success at any time of analysis is greater than 90%, or if the predicted probability of test success at the maximum sample size is less than the invalidity limit of 6.5%. Otherwise, enrollment continues until the next time period for analysis or final sample size. The analysis of the validity endpoint is performed with the final sample size determined for the security endpoint. Efficacy of the efficacy endpoint assessment was > 80% at all sample sizes of N30 subjects.

The primary safety and efficacy endpoints were evaluated using an accurate test of binomial ratios at a single 5% significance level.

To control operational deviations, the timing and results of the period analysis are not revealed to the research investigator unless the period analysis results in a decision to stop enrollment. The session analysis proceeds seamlessly without interrupting study enrollment unless the session analysis indicates to stop enrollment. The statistical personnel performing the interim analysis will not propagate the predicted study success probabilities or summary results calculated at the interim analysis until the final database lock of the CSR.

The analysis of the primary efficacy endpoints included null and alternative hypotheses including Ho: PE <0.80 and Ha: PE > 0.80. It should be understood that Primary Efficacy (PE) may refer to the proportion of patients for whom an acute procedure was successful, where acute procedure success is defined as confirmation of an entry block in the treated pulmonary vein following adenosine and/or isoproterenol challenge (with or without the use of a focal catheter). The per-protocol population was used as the main analysis population. Subjects with missing validity endpoint data will be excluded from the primary analysis. Sensitivity analysis of missing data was performed using PP and populations to assess the impact of missing data on primary efficacy outcomes and described in Statistical Analysis Programs (SAP).

With respect to the ablation parameters of this study, the electrodes 33 of the catheter 24 may come into contact with the tissue due to the length of the balloon 80 and the electrodes, wherein the length of the electrodes each helps to accommodate variable anatomy. Thus, the power required to form a circumferentially continuous lesion in the ostium of the pulmonary vein is less than that of other radio frequency catheters. The power delivery from each electrode is regulated by the generator and determined by user input and temperature readings from a thermocouple located on the electrode.

When used with catheter 24, the perfusion pump of this study delivered a continuous infusion of 5mL/min of room temperature heparinized saline (1u heparin/1 mL saline) without delivering radiofrequency current. To inflate the balloon, 35mL per minute was delivered during ablation using a high flow setting. The recommended operating parameters for catheter 24 are presented in fig. 14.

The duration of the study was approximately 21 months, including the enrollment and follow-up periods. It should be understood that the data presented herein are for illustrative purposes and should not be construed to limit the scope of the disclosed technology in any way or to exclude any alternative or additional embodiments.

This study may demonstrate the clinical safety and acute effectiveness of balloon catheter 24 in the isolation of the atrial pulmonary veins when used with catheter 110 in treating subjects with Paroxysmal Atrial Fibrillation (PAF). In particular, the study may demonstrate clinical safety based on the incidence of early-onset (within 7 days of the mapping and ablation procedure) Primary Adverse Events (PAEs). Fig. 15 shows a table summarizing the intensity or severity of each AE evaluated according to classification. For purposes of this disclosure, an AE may be any undesirable experience (sign, symptom, disease, abnormal laboratory value, or other medical event) that occurs to a subject during a study, whether or not it is associated with a device or procedure. If the investigator determines that physical findings (including vital signs) observed at follow-up or pre-existing physical findings worsening from baseline are clinically significant, they are adverse events. For the study, any physical condition that existed at the time the subject was screened was considered a baseline and was not reported as an AE. Such conditions should be added to the background medical history if not previously reported. However, if the condition of the subject worsens at any time during the study, it may be recorded as an AE. To demonstrate acute effectiveness and/or long-term effectiveness based on the proportion of acute protocol success, success in this context may thus be defined as confirmation of entry block in the treated pulmonary vein following adenosine and/or isoproterenol challenge (including with or without the use of a focal ablation catheter).

Subjects with drug symptomatic PAF are enrolled and the patient population size includes up to 230 evaluable subjects (although fewer or more subjects, including populations such as 80, 130, and 180 subjects, may be studied as needed or desired). The subject can be evaluated pre-protocol, pre-discharge, and 7 days post-protocol (4 to 10 days), 1 month (23 to 37 days), 3 months (76 to 104 days), and 6 months (150 to 210 days).

The primary purpose of the study is to demonstrate the clinical safety and acute effectiveness of catheter 24 in conjunction with catheter 110 in the isolation of the atrial pulmonary veins when treating subjects with paroxysmal atrial fibrillation. In particular, the study attempted to demonstrate clinical safety based on the proportion of early-onset primary adverse events (within 7 days of the ablation procedure) and acute efficacy based on the proportion of acute procedure success, defined as confirmation of entry block in the treated pulmonary vein following adenosine and/or isoproterenol challenge (including with or without the use of a focal ablation catheter).

The primary endpoints of the study included acute efficacy and acute safety. Acute safety may include the incidence of early-onset Primary Adverse Events (PAEs) within 7 days of the initial mapping and ablation procedure using one or more investigational devices. Throughout this disclosure, it should be understood that an Adverse Event (AE) is any adverse medical event in a subject, whether or not it is related to a investigational medical device.

In contrast, the following clinical events were not considered adverse events for this study: minimal pericarditis attributable to ablation procedures, defined as pleuroperineous chest discomfort with or without pericardial friction and ECG changes; pharmacological or synchronized cardioversion of AF/AFL/AT recurrence is required during hospitalization of the exponential ablation procedure, or throughout the duration of the study. However, a new finding of left atrial flutter occurring after ablation is an AE, and re-ablation of AF or pre-existing AFL/AT is not itself an AE, however any procedural complication is considered an AE and should be reported in the applicable timeline.

A Serious Adverse Event (SAE) in the present disclosure is any event that meets one or more of the following criteria: leading to death; causing a severe deterioration in the health of the subject with the result of a life-threatening disease or injury, permanent impairment of a body structure or body function, hospitalization or extension of an existing hospitalization, medical or surgical intervention to prevent a life-threatening disease or injury or permanent impairment of a body structure or body function; resulting in fetal distress, fetal death, or congenital abnormalities or birth defects. It is understood that the planned hospitalization for the present condition prior to enrollment of the subject in the study does not meet the definition of SAE. An AE will meet the criteria of "hospitalization" if an event necessitates entry into a healthcare facility (e.g., an overnight stay). An emergency room visit that does not result in admission is evaluated for one of the other serious consequences. For further reference, fig. 16 is provided which summarizes the classification of the intensity or severity of each AE.

In this study, PAE included the following AEs: device or procedure related deaths, atrial-esophageal fistulas, myocardial infarction, cardiac tamponade/perforation, thromboembolism, stroke/cerebrovascular accident (CVA), Transient Ischemic Attack (TIA), phrenic nerve paralysis, pulmonary vein stenosis, pericarditis, pulmonary edema, macrovascular access complications/bleeding, and hospitalization (incipient or chronic). In the study, events were considered primary AEs, even though they occurred more than one week (7 days) after the protocol. Hospitalization-related events were excluded only due to arrhythmic relapse or non-medically urgent cardioversion.

Secondary endpoints of the study with respect to safety included: the incidence of individual PAEs from the primary composite event; incidence of Severe Adverse Device Effects (SADE); incidence of Severe Adverse Events (SAE) within 7 days (early onset), within >7 to 30 days (perioperative) and within >30 days (late onset) of the initial ablation procedure; the incidence of non-serious adverse events; acute protocol success, defined as confirmation of entry block in the treated Pulmonary Vein (PV) following adenosine challenge (with or without focal catheter); pulmonary Vein Isolation (PVI) supplemental ablation by a focal catheter among all targeted veins and the subject during the index procedure; non-PV triggering using focal catheter ablation during an index procedure; determining no recorded AF/AT/atypical (left) AFL episodes based on electrocardiographic data throughout the validity assessment period (91-365 days after the index protocol), without using class I AAD and class III AAD; the average number of radio frequency applications and the radio frequency time required to isolate a common pulmonary vein; incidence of hospitalization for cardiovascular events (where hospitalization is defined as extended stay ≧ 2 nights after standard index protocol, or stay-days on which the hospitalized patient is misaligned with the index protocol ≧ 1 calendar day); health economics data including, but not limited to, index protocol workflow cost, quality of life (QoL), and hospital cost; the incidence of asymptomatic and symptomatic cerebral embolism as determined by MRI assessment before the procedure and after ablation; frequency, anatomical location and size (diameter and volume) of cerebral embolism assessed by MRI at baseline, post-ablation and during follow-up; incidence of new or worsening neurological deficits at baseline, post-ablation, and at follow-up, compared to baseline summary of NIHSS scores at baseline, post-ablation, and during follow-up; summary of MoCA scores at baseline, 1 month follow-up and during further follow-up; and hospitalization for cardiovascular events (hospitalization is defined as prolonged stay night after the index protocol, or hospitalized patient stays 1 calendar day not coincident with the index protocol).

Secondary endpoints on effectiveness of this study included the percentage (%) of focal catheters in all targeted veins and PVI supplemental ablation by the subject; percent (%) of subjects with non-PV triggering using focal catheter ablation; (ii) percentage (%) of subjects with no recorded symptomatic Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left side) Atrial Flutter (AFL) episodes (> 30 seconds of episodes from day 91 to day 180 on arrhythmia monitoring device); and the percentage (%) of subjects with no recorded Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left-sided) Atrial Flutter (AFL) episodes (> 30 seconds of episodes from day 91 to day 180 on arrhythmia monitoring devices).

Secondary endpoints of the study for additional analysis of the protocol characteristics include, but are not limited to, total protocol time, ablation time, radio frequency application time, balloon dwell time, time to achieve PVI, number and time of radio frequency applications per PV location, and fluoroscopy time and dose.

Secondary endpoints of the study on health economics assessments include index protocol workflow costs, hospital costs and quality of life.

The incidence of pre-and post-ablation symptomatic and asymptomatic cerebral embolism in subjects enrolled in the NAE (neurological assessment evaluable) subgroup was assessed in the absence of neurological symptoms (asymptomatic) or in the presence of embolism-associated neurological symptoms (symptomatic). The NAE subgroup is a prospective design with serial enrollment. The enrolled subjects may not qualify as a subset of the NAE. The method minimizes confounding effects of the learning curve during early use of the medical device. If study enrollment ended early after observation during the planning period, the enrollment NAE sub-group may terminate before the target 40 subjects were achieved.

Subjects enrolled in the improved intent-to-treat (mITT) population included enrolled subjects meeting eligibility criteria, and a study catheter was inserted. The Safety Population (SP) included all enrolled subjects who had inserted the study catheter. The Per Protocol (PP) population is a subset of the mITT population and includes subjects who have been enrolled and met all eligibility criteria, have been radio frequency ablated with a study catheter, and have been treated for study-related arrhythmias.

The primary efficacy endpoints for clinical efficacy in the study were determined by the following events: no recorded AF, Atrial Tachycardia (AT), or atypical (left) Atrial Flutter (AFL) episodes (e.g., >30 seconds on arrhythmia monitoring devices) were based on electrocardiographic data over the entire validity assessment period (days 91 to 365 after the exponential procedure). In addition, a subject is considered to have a chronic efficacy failure if the subject meets any of the following criteria: acute procedure failure (i.e., failure to confirm entry block in clinically relevant pulmonary veins after the procedure); after the blanking period (after day 90 post-index protocol), repeated ablation or surgical treatment for AF/AT/atypical (left-sided) AFL; DC cardioversion for AF/AT/atypical (left-sided) AFL after the blanking period (after day 90 post-exponential protocol); continuous AF/AT/AFL on a standard 12-lead ECG, even if the duration of the recording is shorter than 30 seconds (after day 90 after the exponential procedure); prescribing new class I and/or class III AAD for AF during a validity assessment period (e.g., 91-365 days after the index protocol), or prescribing during a blank period and the subsequent passage of 90 days; during the effectiveness evaluation period (e.g., day 91 to day 365 after the index protocol), previously failed class I AAD and/or class III AAD (failed at or before screening) were taken at a dose greater than the highest ineffective historical dose for AF; and amiodarone is prescribed after the exponential ablation procedure.

During this study, current AF management guidelines and institutional standards of care practice follow AAD therapy as closely as possible. Figure 16 shows a table demonstrating the classification in the study based on AAD treatments administered during and after the washout period.

It should be understood that prior to the procedure, uninterrupted anticoagulation therapy is in place at least 1 month prior to the ablation procedure. If warfarin/coumarin therapy is received, the subject has an International Normalized Ratio (INR) of 2 or greater for at least 3 weeks prior to treatment, and it must be confirmed that the subject has an INR of 2 or greater within 48 hours prior to the procedure. Any INR <2 within 3 weeks prior to ablation is understood to result in the subject being excluded or the study protocol being postponed until INR ≧ 2 for at least 3 weeks prior to treatment. Anticoagulation therapy is not discontinued or stopped prior to the protocol (e.g., no dose should be missed or missed), and the daily regimen is continued.

During the procedure, a bolus of heparin is administered prior to transseptal puncture and an ACT of 350 to 400 seconds is targeted prior to insertion of balloon 80 and throughout the procedure. The ACT level is checked every 15 to 30 minutes during the protocol to ensure an ACT target of 350 to 400 seconds. All records (ACT levels, heparin administration timing and dose) were recorded in medical records as source files. All tubing and sheaths were flushed continuously with heparinized saline.

After the procedure, it is strongly recommended to administer anticoagulant therapy at least 2 months after ablation. The additional drugs required to treat the clinical indication are determined by the clinical investigator, and the management of AAD during the study is determined by the investigator.

Secondary endpoints of effectiveness include: acute protocol success, defined as confirmation of entry block in the treated pulmonary vein following adenosine challenge (with or without focal catheter); PVI supplemental ablation by the focal catheter among all targeted veins and the subject during the index procedure; non-PV triggering using focal catheter ablation during an index procedure; determining no recorded episodes of symptomatic AF/AT/atypical (left-sided) AFL, without class I antiarrhythmic drugs (AAD) and class III AAD, based on electrocardiographic data over the entire validity assessment period (91-365 days after the exponential protocol); and the average number of rf applications and rf time required to isolate the common pulmonary vein.

Patient selection

Criteria for patient selection, method or use, personnel, facilities and training specified in the study are intended to minimize the risk to the subject undergoing the procedure.

Patients were carefully prescreened prior to inclusion in the study to ensure that inclusion and exclusion criteria were met. The risk of Phrenic Nerve Paralysis (PNP) is minimized by monitoring the Phrenic Nerve (PN) with a pacing strategy prior to ablation. If evidence of PN damage is observed, ablation is immediately stopped and the balloon can be repositioned. By not positioning the balloon within the tubular portion of the target PV, the risk of PV stenosis can be minimized. When the catheter is positioned inside the pulmonary vein, the balloon should not be inflated; instead, the balloon will always be inflated in the atrium and then positioned at the PV ostium.

The risk of Asymptomatic Cerebral Embolism (ACE) may be minimized by implementing an anticoagulation protocol before balloon introduction into the left atrium and during the procedure to avoid thrombosis/embolism during the procedure. The investigator was instructed to remove air bubbles and minimize catheter exchanges during the procedure to reduce the risk of introducing air. A single transseptal technique of administering a bolus of heparin prior to transseptal puncture has also been implemented. To help prevent esophageal injury, studies require intraluminal esophageal temperature monitoring.

After the rule, all subjects maintained systemic oral anticoagulation therapy for at least two months after the protocol, beginning within 6 hours after the protocol. After two months after the procedure, a decision is made regarding continued use of the systemic anticoagulant based on the subject's risk of thromboembolism. Patients aged 75 years or older with congestive heart failure hypertension, aged 65 to 74 years with diabetic stroke, TIA or TE vascular disease, gender type (female) (hereinafter referred to as "CH" or "CH") and_A2DS2-VASc ") score ≥ 2, systemic oral anticoagulation can last for more than two months after ablation.

Age, gender and cardiovascular risk factors (e.g., diabetes, obesity, smoking, hypertension, hyperlipidemia) were recorded for each included patient. According to the hospital protocol, the initial imaging is brain CT in combination with cervical and intracranial angiography or brain MRI in combination with time-of-flight angiography. The ASPECT (early CT for Alberta stroke program) score was evaluated by an experienced neuroradiologist in either modality, and the NIHSS score was evaluated by a neurologist. In the case of a post-wake stroke, the patient receives treatment for up to 12 hours from the onset of the stroke or the last known good time.

Inclusion criteria for this study included the following:

at least three (3) symptomatic episodes of AF with an episode duration of ≧ 1 minute within six (6) months prior to enrollment, and at least one (1) episode of AF must be recorded by electrocardiogram within twelve (12) months prior to enrollment. Electrocardiographic recordings may include, but are not limited to, Electrocardiograms (ECGs), holter monitors, or telemetry strips;

selected for an AF ablation protocol for pulmonary vein isolation; being able and willing to comply with ongoing compliance requirements;

disabling at least one (1) class I or class III AAD, as evidenced by recurrent symptomatic AF or intolerable side effects against AAD;

willingness to comply with anticoagulation requirements (e.g., warfarin, rivaroxaban, dabigatran, apixaban);

age: from 18 to 75 years old; and

ability and willingness to comply with all pre-protocol, post-protocol and follow-up test and access requirements. Exclusion criteria for this study included the following:

AF secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac causes;

previous surgical or catheter ablation for AF;

ablation is expected to be received outside of the PV ostium and CTI region (e.g., AVRT, AVNRT, atrial tachycardia, VT, and WPW);

Previously diagnosed as having sustained or long-lasting AF and/or >7 days of continuous AF, or >48 hours of pre-cardioversion symptoms;

any percutaneous coronary intervention performed within the last 2 months;

valve repair or replacement, or the presence of a prosthetic valve;

any carotid stenting or endarterectomy performed;

any carotid stenting or endarterectomy was performed.

Coronary Artery Bypass Grafting (CABG), cardiac surgery (e.g., a ventricular incision, an atrial incision), or heart valve surgery or percutaneous surgery have been performed within the past 6 months.

Left Atrial (LA) thrombus recorded on baseline/pre-protocol imaging.

Anterior and posterior atrial diameter >50mm

Diameter of any PV 26mm

Left Ventricular Ejection Fraction (LVEF) < 40%.

Anticoagulation (e.g., heparin) contraindications.

A history of clotting or bleeding abnormalities.

Myocardial infarction occurred within the past 2 months.

Thromboembolic events (including transient ischemic attacks [ TIA ]) were recorded over the past 12 months.

Rheumatic heart disease.

Uncontrolled heart failure or class III or IV function of the New York Heart Association (NYHA).

Wait for a heart transplant or other heart surgery within the next 12 months.

Unstable angina pectoris.

Acute disease or active systemic infection or sepsis.

Diagnosis of atrial myxoma or atrial septa or patches.

The presence of an implanted pacemaker or Implantable Cardioverter Defibrillator (ICD), or embedded tissue or ferrous metal fragments.

A major lung disease (e.g., restrictive lung disease, constrictive or chronic obstructive pulmonary disease) or any other disease or dysfunction of the lung or respiratory system that produces chronic symptoms.

Major congenital abnormalities or medical problems that investigators believe will discourage enrollment in this study.

Pregnancy (in the case of menopause, confirmed by pregnancy tests), lactation or women at birth age and scheduled to become pregnant during the course of this clinical investigation.

Enrollment in an investigative study evaluating another device, biological agent or drug.

With known stenosis of the pulmonary vein.

The presence of an intramural thrombus, tumor or other abnormality that obstructs vascular access or manipulation of the catheter.

Presence of IVC filter

Presence of disorders that obstruct vascular access.

Life expectancy shorter than 12 months or with other disease processes that may limit survival to shorter than 12 months.

Presenting contraindications to the devices used in the study (e.g., TTE, CT, etc.), as indicated in the corresponding instructions for use.

Classified as a vulnerable group and requiring special treatment with respect to health care

Additional exclusion criteria for assessable (NAE) subjects for neurological assessment including contraindications

The patient took amiodarone at any time during the past 3 months prior to enrollment;

contraindications for the use of MRI contrast agents, such as end stage renal disease and the like (judged by PI), the presence of iron-containing metal fragments in the body, and

unresolved preexisting neurological deficits.

Results of the study

During the study, the investigators collected the following data: rf ablation parameters per PV, number of rf applications per target PV, number of rf applications required to use a focal catheter (if applicable), total rf duration per target PV, total time to apply rf with balloon catheter 24 until PV isolation of the targeted vein is achieved (TTI-isolation time), total time to rf apply using a focal catheter (if applicable), PV acute reconnection, rf ablation parameters per application, targeted vein, number of ablations by generator, total duration of rf energy per application, balloon inflation index before target PV application, pacing electrodes, ablation parameters (impedance, temperature, power, number of active electrodes per application, and total duration of rf application. Including but not limited to: the percentage of target PV isolated on first freeze and the percentage of target PV with acute reconnection; protocol parameters including, but not limited to: duration of time when mapping (LA and PV), total radio frequency duration (duration of radio frequency energy delivered by multi-electrode radio frequency balloon catheter and focal catheter (if applicable)), total PVI time using balloon catheter (duration from first radio frequency application to last radio frequency application), total PVI time using focal catheter (if applicable), total protocol time (from first femoral puncture to removal of catheter), total fluoroscopy time and dose, total balloon dwell time (from first insertion of radio frequency balloon until removal of radio frequency balloon), ECG data, total fluid delivered via ablation catheter, total fluid delivered via intravenous catheter (if captured), fluid output (if captured), net fluid input, ACT level and time point of heparin administration, strategies to assess proximity to phrenic nerve, Strategies for minimizing the risk of esophageal injury, the type of temperature probe, the cutoff temperature, and any abnormal increase in observed temperature.

Fig. 17 depicts a method or use 1700 of administering a protocol for treating atrial fibrillation. The method or use 1700 may include 1710 delivering a multi-electrode radio frequency balloon catheter to one or more targeted pulmonary veins; 1720 ablating tissue of the pulmonary vein using the multi-electrode radio frequency balloon catheter; and 1730 achieve a predetermined pulmonary vein isolation effectiveness rate.

Fig. 18 depicts a method or use 1800 of administering a protocol for treating atrial fibrillation. The method or use 1800 may include 1810 delivering a multi-electrode radio frequency balloon catheter to a pulmonary vein; 1820 ablating tissue of the pulmonary vein using the multi-electrode radio frequency balloon catheter; and 1830 achieve a predetermined pulmonary vein isolation effectiveness rate.

Fig. 19 depicts a method or use 1900 of administering a protocol for treating atrial fibrillation. The method or use 1900 may include 1910 delivering a multi-electrode radio frequency balloon catheter to a pulmonary vein; 1920 ablating tissue of the pulmonary vein using the multi-electrode radio frequency balloon catheter; and 1930 achieves pulmonary vein isolation and a safety endpoint of at least 97% within seven (7) days of successful pulmonary vein isolation.

Fig. 20 depicts a method or use 2000 of administering a protocol for treating atrial fibrillation. The method or use 2000 may include 2010 delivering a multi-electrode radio frequency balloon catheter to a pulmonary vein; 2020 ablating tissue of the pulmonary vein using the multi-electrode radio frequency balloon catheter; and 2030 achieves pulmonary vein isolation and a safety endpoint of at least 90% within seven (7) days of successful pulmonary vein isolation.

Fig. 21 depicts a method or use 2100 of administering a protocol for treating atrial fibrillation. The method or use 2100 can include 2110 delivering a multi-electrode diagnostic catheter and a multi-electrode rf balloon catheter having a plurality of individually controllable electrodes for rf ablation to one or more targeted pulmonary veins; 2120 ablating one or more tissues targeted to the pulmonary veins using one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter; 2130 diagnosing one or more targeted pulmonary veins using the multi-electrode diagnostic catheter; and 2140 is based on using a multi-electrode radio frequency balloon catheter and a multi-electrode diagnostic catheter in isolation of one or more targeted pulmonary veins to achieve at least one of a predetermined clinical effectiveness and acute effectiveness of the method or use.

Fig. 22 depicts a method or use 2200 for treating paroxysmal atrial fibrillation in a plurality of patients. Method or use 2200 may include 2210 delivering a multi-electrode diagnostic catheter and a multi-electrode radio frequency balloon catheter having a plurality of individually controllable electrodes for radio frequency ablation to one or more targeted pulmonary veins; 2220 ablating one or more tissues targeted to the pulmonary veins using one or more of the plurality of electrodes of the independently controlled multi-electrode radiofrequency balloon catheter; 2230 diagnosing all targeted pulmonary veins using a multi-electrode diagnostic catheter; and 2240, during and about 6 months after the method or use, achieves a predetermined adverse event rate based on the use of the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter in isolation of all targeted pulmonary veins.

Fig. 23 depicts a method or use 2300 for treating paroxysmal atrial fibrillation in a plurality of patients. Method or use 2300 may include 2310 assessing the number and size of all targeted pulmonary veins and anatomical structures of the left atrium; 2320 puncturing the transseptal space; 2330 selectively position the multi-electrode esophageal temperature monitoring device in the vasculature relative to all targeted pulmonary veins; 2340 selectively positioning a multi-electrode radio-frequency balloon catheter in the vasculature relative to all targeted pulmonary veins, the multi-electrode radio-frequency balloon catheter having a plurality of individually controllable electrodes for radio-frequency ablation; 2350 ablate all tissue targeting the pulmonary vein with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter; 2360 confirm isolation of all targeted pulmonary veins using a multi-electrode diagnostic catheter; 2370 confirming the presence of all portal blockages in the targeted pulmonary veins; and 2380 based on the confirmation of the presence of the portal block, achieving a predetermined clinical effectiveness and/or acute effectiveness of the method or use, the predetermined clinical effectiveness and/or acute effectiveness being associated with isolating all targeted pulmonary veins according to the method or use.

Figure 24 shows a table summarizing single freeze isolation versus non-isolation for studies according to the present disclosure. Specifically, fig. 24 summarizes single freeze isolation versus non-isolation as a function of ablation location, number of electrode ablations, initial impedance, impedance drop, maximum temperature, and temperature rise. With respect to the number of electrode ablations, only the first ablation with full circumference ablation and full duration ablation was included for analysis. Accordingly, the study investigated certain endpoints of the study as potential predictors of successful isolation. One endpoint investigated included duration and energy, whereby longer duration and higher energy were evaluated in order to induce higher rates of single-freeze PVI, as shown and discussed herein.

Another endpoint included the isolation time, but no significant effect on ablation success was observed. Another endpoint included the inflation index, but no significant effect on ablation success was observed. Another endpoint includes an initial impedance, whereby higher initial impedance changes among the full circumference electrodes are evaluated in order to result in a lower rate of single-shot frozen PVI (e.g., <30 Ω), as shown and discussed herein. Another endpoint includes a drop in impedance, whereby the difference in the drop in impedance between the anterior and posterior walls is evaluated as a possible indicator of ablation success, as shown and discussed herein. Another endpoint included a maximum temperature, but no significant effect on the success of the ablation was observed.

Fig. 25 shows a graph summarizing the initial impedance of studies according to the present disclosure. In particular, fig. 25 shows the mean difference in initial impedance between single cryo-isolated (no reconnection), isolated (reconnection), and non-isolated anterior and posterior walls for patients evaluated in the studies of the present disclosure.

Figure 26 shows a graph summarizing temperature rises according to studies of the present disclosure. In particular, fig. 26 shows the average difference in temperature rise between single cryo-isolated (no reconnect), isolated (reconnect), and non-isolated anterior and posterior walls for patients evaluated in the study of the present disclosure.

Fig. 27 shows a graph summarizing the impedance drops of studies according to the present disclosure. In particular, fig. 27 shows the mean difference in impedance drop between single cryo-isolated (no reconnection), isolated (reconnection), and non-isolated anterior and posterior walls for patients evaluated in the studies of the present disclosure. In this study, the difference in impedance drop between the anterior and posterior walls was determined as a possible indicator of ablation success.

Fig. 28 shows a graph summarizing the maximum temperatures of studies according to the present disclosure. In particular, fig. 28 shows the maximum temperature mean difference between single cryo-isolated (no reconnect), isolated (reconnect), and non-isolated anterior and posterior walls for patients evaluated in the study of the present disclosure.

Fig. 29A shows a graph summarizing initial impedance changes among full circumference electrodes in the study of the present disclosure. Specifically, fig. 29A summarizes the average initial impedance changes among single cryo-isolated (no reconnection), isolated (reconnection), and non-isolated full circumference electrodes for patients evaluated in the studies of the present disclosure. Note that only the first ablation with full circumference ablation and full duration ablation is included for analysis. Fig. 29B shows a table summarizing initial impedance changes among full circumference electrodes in the study of the present disclosure.

Figure 30 shows a graph summarizing single freeze PVI rates in studies of the present disclosure as a function of initial impedance change among full circumference electrodes. For 27 patients evaluated to be approximately less than about 20 Ω, a single-freeze PVI of about 85.2% was observed. For 77 patients evaluated to be approximately between 20 Ω to 30 Ω, a single-freeze PVI of about 77.9% was observed. For 61 patients evaluated to be approximately between 30 Ω to 40 Ω, a single-freeze PVI of about 75.4% was observed. For 34 patients evaluated approximately between about 40 Ω to 50 Ω, a single-freeze PVI of about 67.6% was observed. For 11 patients evaluated approximately between about 50 Ω to 60 Ω, a single-freeze PVI of about 36.4% was observed. For 9 patients evaluated to be approximately greater than about 60 Ω, a single-freeze PVI of about 33.3% was observed.

Figure 31 shows a graph summarizing the isolation times in a study of the present disclosure for patients evaluated in a study of the present disclosure, where the isolation times include a single freeze isolation (no reconnection) at approximately about 8.1 seconds and an isolation (reconnection) at approximately about 10.9 seconds.

Figure 32 shows a graph summarizing the inflation index in the study of the present disclosure for single cryo-isolation (no reconnection), isolation (reconnection), and non-isolation of patients evaluated in the study of the present disclosure.

Fig. 33 shows a table summarizing pre-ablation and post-ablation parameters for the studies of the present disclosure with respect to impedance, change in impedance, lowest initial impedance, mean initial impedance, change in initial impedance, lowest maximum temperature, lowest impedance drop, mean impedance drop, and change in impedance drop. Excluded from the group cases, only the first freeze using full circumference (e.g., full electrode burn) and full duration (e.g., 60 seconds) per PV was evaluated for analysis, including a total of 219 ablations using 158 single cryoisolations. Each parameter, which is a potential predictor of single freeze isolation (including LCPV and RMPV), was evaluated using Minitabe pearson correlation and a binary logistic regression model. It should be understood that the larger the coefficients of the table in fig. 33 and the lower the P value, the better the predictor. In this analysis, the pre-ablation parameters mean initial impedance and initial impedance change are considered predictors of single cryoisolation. With respect to post-ablation parameters, the lowest impedance drop and the change in impedance drop are similarly considered predictors of single cryoisolation.

Fig. 34 shows a table summarizing pre-ablation parameters for initial temperature, initial impedance, and initial anterior wall impedance in studies of the present disclosure. Predictors of single freeze isolation are those observed using correlation P values <0.01, including maximum initial temperature, initial temperature change, average initial impedance, maximum initial impedance, initial impedance change, average initial anterior wall impedance, lowest anterior wall impedance, maximum anterior wall impedance, and anterior wall impedance change. It should be understood that the front wall impedance value is the impedance value among the front wall electrodes. Each parameter, which is a potential predictor of single freeze isolation (including LCPV and RMPV), was evaluated using Minitabe pearson correlation and a binary logistic regression model.

Fig. 35 shows a table summarizing post-ablation parameters for temperature slope, temperature rise, maximum temperature, impedance drop, and percentage impedance drop (e.g., impedance drop/initial impedance) in studies of the present disclosure. Predictors of single freeze isolation are those observed using a correlation P value of <0.01, including average temperature slope, lowest temperature slope, average temperature rise, lowest impedance drop, change in impedance drop, percent lowest impedance drop, and percent change in impedance drop. Each parameter, which is a potential predictor of single freeze isolation (including LCPV and RMPV), was evaluated using Minitabe pearson correlation and a binary logistic regression model. As can be seen from fig. 34 to 35, the average and the highest values of the initial impedance and the front wall initial impedance have a high correlation with the single-shot freezing isolation rate (P value < 0.0005). The optimal range (single freeze isolation > 90%) is <95 Ω for the average initial impedance and <110 Ω for the highest initial impedance.

Based on the data from the SHINE study (with duplicates in appendix 4), it is believed that there are six (6) single parameter predictors for single freeze isolation ("SSI") and eight (8) single parameter evaluators for SSI. The "predictor" allows for determining whether a relevant parameter (i.e., a pre-ablation parameter) observed or measured (using a research device as described herein) prior to ablation would likely result in a success rate of 90% or greater based on data collected from the study. On the other hand, the "evaluation factor" allows determining whether the actual ablation performed will likely result in a success rate of 90% or higher of SSI. The "predictors" and "evaluators" are summarized in table 1 below:

TABLE 1 Single parameter predictors and evaluators

Fig. 36 shows a table summarizing information from table 1 above believed to be a potential ranking of pre-and post-ablation parameters, which are single-freeze predictors observed in studies of the present disclosure. With respect to pre-ablation parameters, the ranking of the single-freeze predictors from first to fifth are initial impedance change, highest initial temperature, initial temperature change, pre-impedance change, and lowest pre-impedance, respectively. With respect to the post-ablation parameters, the ranking of the single-freeze predictors from first to sixth was the initial impedance drop change, lowest temperature rise, lowest impedance drop, lowest temperature slope, average temperature slope, and average temperature rise, respectively. In other words, the most accurate predictors of single-shot cryo-isolation rate prior to ablation are: (a) achieving small variations in impedance (e.g., <20 Ω) and temperature (<3 ℃) among the 10 electrodes, (b) limiting the highest initial temperature of the 10 electrodes (e.g., <31 ℃), and (c) allowing the lowest front wall impedance to be in the approximate range of about 80 Ω to 90 Ω.

Fig. 37 shows a graph summarizing the correlation between the mean initial impedance and the age of the patient in the study of the present disclosure. Fig. 38 shows a graph summarizing the correlation between the mean initial impedance and the BMI of the patient in the study of the present disclosure. Fig. 39 shows a graph summarizing the correlation between initial temperature and temperature rise in the study of the present disclosure. Fig. 40 shows a graph summarizing the correlation between initial temperature and temperature slope in the study of the present disclosure. Fig. 41 shows a graph summarizing the correlation between the initial temperature and the initial impedance in the study of the present disclosure. Fig. 42 shows a graph summarizing the correlation between initial temperature and resistance drop in the study of the present disclosure. Fig. 43 shows a graph summarizing the correlation between the initial temperature change and the highest initial temperature in the study of the present disclosure. Fig. 44 shows a graph summarizing the correlation between the initial temperature change and the impedance drop change in the study of the present disclosure. Fig. 45 shows a graph summarizing the correlation between the initial temperature change and the temperature rise change in the study of the present disclosure.

Fig. 46 shows a graph summarizing the correlation between initial temperature change and temperature slope change in the study of the present disclosure. Fig. 47 shows a graph summarizing the correlation between initial impedance and temperature rise in the study of the present disclosure. Fig. 48 shows a graph summarizing the correlation between initial impedance and temperature slope in the study of the present disclosure. Fig. 49 shows a graph summarizing the correlation between initial impedance and impedance drop in the study of the present disclosure. Fig. 50 shows a graph summarizing the correlation between initial impedance and percentage of impedance drop in studies of the present disclosure. Fig. 51 shows a graph summarizing the correlation between the initial impedance change and the initial temperature change in the study of the present disclosure. Fig. 52 shows a graph summarizing the correlation between the initial impedance change and the impedance drop change in the study of the present disclosure. Fig. 53 shows a graph summarizing the correlation between the initial impedance change and the highest initial impedance in the study of the present disclosure. Fig. 54 shows a graph summarizing the correlation between the initial impedance change and the average initial impedance in the study of the present disclosure.

Fig. 55 shows a graph summarizing the correlation between the initial impedance change and the lowest impedance drop in the study of the present disclosure. Fig. 56 shows a graph summarizing the correlation between the lowest temperature rise and the lowest impedance drop in the study of the present disclosure. Fig. 57 shows a graph summarizing the correlation between the lowest impedance drop and the lowest temperature slope in the study of the present disclosure. Fig. 58 shows a graph summarizing the correlation between the lowest temperature rise and the lowest temperature slope in the study of the present disclosure.

Figure 59 shows a schematic summarizing correlated datasets for single freeze-isolation predictors studied according to the present disclosure. In particular, fig. 59 demonstrates that pre-ablation parameter datasets such as temperature rise, initial temperature, and temperature slope are believed to have strong correlations with single-freeze isolation predictors for single-freeze isolation. Similarly, fig. 59 demonstrates that pre-ablation parameter datasets such as impedance drop changes, initial impedance changes, and highest initial impedance are considered to have a strong correlation with single cryoisolation predictors for single cryoisolation. It is contemplated that the solution of the present disclosure may use multiple parameters (as opposed to a single parameter of the predictor and estimator factors referenced in the table) such as initial temperature change, maximum initial temperature, initial impedance change, and maximum initial impedance as the pre-ablation predictor of a single cryoisolation. Table 2 summarizes the parameters for the multi-parameter predictors and evaluators.

Table 2: multi-parameter predictor and evaluator

Figure 60 shows a schematic summarizing correlated datasets for single freeze isolation assessment factors according to a study of the present disclosure. Fig. 60 demonstrates that post-ablation parameter datasets such as minimum temperature slope, minimum temperature rise, minimum impedance drop, change in impedance drop, minimum impedance drop, and change in impedance drop are considered to have strong correlations with a single cryoisolation assessment factor for single cryoisolation. It is contemplated that the solution of the present disclosure may use one or more of these parameters as a post-ablation evaluation factor for a single cryo-isolation. In view of the foregoing, one exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～4.367-0.420ΔT₀-0.0486ΔZ₀

Wherein the single freeze isolation probability is a function of two parameters: initial impedance change (Δ T)₀) And initial temperature change(ΔZ₀)。

Fig. 61A shows a computer simulation model that performs the aforementioned single freeze isolation probability algorithm, while fig. 61B-61C show tables summarizing data associated with the simulation of fig. 61A.

Another exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～26.78-0.576T_0max-0.0632Z_0max

wherein the predictor algorithm includes two parameters: maximum initial temperature (T)_0max) And highest initial impedance (Z)_0max). Fig. 62A shows a computer simulation model that performs the foregoing exemplary algorithm, while fig. 62B-62C show tables summarizing data associated with the simulation of fig. 62A.

Another exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～27.70-0.540T_0max-0.0959Z_0max

wherein the predictor algorithm includes two parameters: maximum initial temperature (T)_0max) And highest initial impedance (Z)_0max). Fig. 63A shows a computer simulation model that performs the foregoing exemplary algorithm, while fig. 63B-63C show tables summarizing data associated with the simulation of fig. 63A.

Another exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～9.31-0.408ΔT₀-0.0544Z_0max

Wherein the predictor algorithm includes two parameters: initial temperature change (Δ T)₀) And highest initial impedance (Z)_0max). FIG. 64A shows a computer simulation model that executes the foregoing exemplary algorithm, while FIGS. 64B-64C show tables summarizing data associated with the simulation of FIG. 64A.

Another exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～11.53-0.439ΔT0-0.0856Z_0mean

wherein the predictor algorithm includes two parameters: initial temperature change (Δ T)₀) And average initial impedance (Z)_0mean). Fig. 65A shows a computer simulation model that executes the foregoing exemplary algorithm, while fig. 65B-65C show tables summarizing data associated with the simulation of fig. 65A.

Another exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～22.61-0.622T_0max-0.0626ΔZ₀

wherein the predictor algorithm includes two parameters: maximum initial temperature (T)_0max) And initial impedance change (Δ Z)₀). Fig. 66A shows a computer simulation model that performs the foregoing exemplary algorithm, while fig. 66B-66C show tables summarizing data associated with the simulation of fig. 66A.

Another exemplary algorithm contemplated for use as a predictor for single freeze isolation includes the following:

Y～26.52+0.013ΔT₀-0.594T_0max-0.0122ΔZ₀-0.0535Z_0maxWherein the predictor algorithm includes four parameters: initial temperature change (Δ T)₀) Maximum initial temperature (T)_0max) Initial impedance change (Δ Z)₀) And highest initial impedance (Z)_0max). FIG. 67 shows a table summarizing data associated with a simulation of the exemplary algorithm.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～1.562+0.2856ΔT_min-0.0629ΔZ_drop

wherein the evaluation factor algorithm includes two parameters: minimum temperature rise (Δ T)_min) And change in impedance drop (Δ Z)_drop). Fig. 68A shows a computer simulation model that executes the foregoing exemplary algorithm, while fig. 68B-68C show tables summarizing data associated with the simulation of fig. 68A.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～-0.507+0.206ΔT_min+0.083Z_dropmin

wherein the evaluation factor algorithm includes two parameters: minimum temperature rise (Δ T)_min) And minimum impedance drop (Z)_dropmin). FIG. 69A shows a computer simulation model that executes the foregoing exemplary algorithm, while FIGS. 69B-69C show tables summarizing data associated with the simulation of FIG. 69A.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～1.248+0.2486ΔT_min-0.0594ΔZ_drop+0.0419Z_dropmin

wherein the evaluation factor algorithm includes three parameters: minimum temperature rise (Δ T) _min) Change in impedance drop (Δ Z)_drop) And minimum impedance drop (Z)_dropmin). Fig. 70A-70B show tables summarizing data associated with simulations of the exemplary algorithms referenced above.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～1.174+0.2515ΔT_min-0.0564ΔZ_drop％

wherein the evaluation factor algorithm includes two parameters: minimum temperature rise (Δ T)_min) And percent change in impedance drop (Δ Z)_drop%). Fig. 71A shows a computer simulation model that performs the foregoing exemplary algorithm, while fig. 71B-71C show tables summarizing data associated with the simulation of fig. 71A.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～-0.644+0.170ΔT_min+0.107Z_drop％_min

wherein the evaluation factor algorithm includes two parameters: minimum temperature rise (Δ T)_min) And percent decrease in minimum impedance (Z)_drop％_min). FIG. 72A shows a computer simulation model that performs the foregoing exemplary algorithm, while FIGS. 72B-72C show numbers that would be associated with the simulation of FIG. 72AAccording to the summary table.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～0.339+0.187ΔT_min+0.0737Z_drop％_min-0.0368ΔZ_drop％

wherein the evaluation factor algorithm includes three parameters: minimum temperature rise (Δ T)_min) Percent decrease in minimum impedance (Z) _drop％_min) And percent change in impedance drop (Δ Z)_drop%). Fig. 73A-73B show tables summarizing data associated with simulations of the exemplary algorithms referenced above.

Another exemplary algorithm contemplated for use as an evaluation factor for single freeze isolation includes the following:

Y～1.043+0.777T′_min+0.171ΔT_min+0.0479Z_drop-min-0.0589ΔZ_dropwherein the evaluation factor algorithm includes four parameters: lowest temperature slope (T'_min) Minimum temperature rise (Δ T)_min) Minimum impedance drop (Z)_drop-min) And change in impedance drop (Δ Z)_drop). FIG. 74 shows a table summarizing data associated with a simulation of the reference evaluation factor algorithm.

Fig. 75A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation average initial temperatures, while fig. 75B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation average initial temperatures in studies of the present disclosure. It can be seen that at average initial temperatures of approximately less than about 28 ℃, the single freeze isolation rate is approximately about 90%. The P value of fig. 75B is 0.016 and the odds ratio (95% CI) is 0.714(0.536 to 0.951).

Fig. 76A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation lowest initial temperatures, while fig. 76B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation lowest initial temperatures in studies of the present disclosure. The single freeze isolation rate is approximately about 90%. The P value of FIG. 76B is 0.191 and the odds ratio (95% CI) is 0.815(0.580 to 1.111).

Fig. 77A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation maximum initial temperatures, while fig. 77B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation maximum initial temperatures in studies of the present disclosure. When the maximum initial temperature is less than about 31 ℃, the single freeze isolation rate is approximately about 90%. The P value of FIG. 77B is 0.000 and the odds ratio (95% CI) is 0.609(0.448 to 0.828).

Fig. 78A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation initial temperature changes, while fig. 78B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation initial temperature changes in studies of the present disclosure. The single pass freeze isolation rate is approximately greater than about 95% when the initial temperature change is less than about 3 ℃. The P value of fig. 78B was 0.002 and the odds ratio (95% CI) was 0.624(0.460 to 0.847).

Fig. 79A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation distributed initial temperatures, while fig. 79B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation distributed initial temperatures in studies of the present disclosure. It can be seen that at distributed initial temperatures of approximately greater than about 31 c, the single freeze isolation rate is approximately greater than about 90%. The P value of fig. 59B was 0.040, and the odds ratio (95% CI) was 0.832(0.699 to 0.991).

Fig. 80A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation distributed initial temperatures, while fig. 79B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation distributed initial temperatures in studies of the present disclosure. It can be seen that at distributed initial temperatures of approximately greater than about 30 ℃, the single freeze isolation rate is approximately greater than about 90%. The P value of fig. 60B was 0.068, and the odds ratio (95% CI) was 0.886(0.777 to 1.010).

Fig. 81A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation distributed initial temperatures, while fig. 81B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation distributed initial temperatures in studies of the present disclosure. It can be seen that at distributed initial temperatures of approximately greater than about 29 ℃, the single freeze isolation rate is approximately about 90%. The P value of fig. 81B was 0.019, and the odds ratio (95% CI) was 0.872(0.776 to 0.980).

Fig. 82A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation average initial impedance, while fig. 82B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation average initial impedance in studies of the present disclosure. It can be seen that the single freeze isolation rate is approximately greater than about 91.7% in the optimal range of approximately less than about 95 Ω. The P value of fig. 82B was 0.000 and the odds ratio (95% CI) was 0.916(0.877 to 0.956).

Fig. 83A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation lowest initial impedance, while fig. 83B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation lowest initial impedance in studies of the present disclosure. The P value of fig. 83B was 0.026, and the odds ratio (95% CI) was 0.950(0.906 to 0.995).

Fig. 84A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation highest initial impedance, while fig. 84B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation highest initial impedance in studies of the present disclosure. It can be seen that in the optimal range of approximately less than about 110 Ω, the single freeze isolation rate is approximately greater than about 91.7%. The P value of fig. 84B is 0.000 and the odds ratio (95% CI) is 0.945(0.922 to 0.969).

Fig. 85A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation initial impedance changes, while fig. 85B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation initial impedance changes in studies of the present disclosure. It can be seen that the single freeze isolation rate is approximately greater than about 88.5% in the optimal range of approximately less than about 20 Ω. The P value of fig. 85B is 0.000 and the odds ratio (95% CI) is 0.950(0.927 to 0.975).

Fig. 86A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation initial anterior wall impedance, while fig. 86B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation initial anterior wall impedance in studies of the present disclosure. It can be seen that in the optimal range of approximately less than about 95 Ω, the single freeze isolation rate is almost approximately between 87% and 89.7%. The P value of fig. 86B is 0.000 and the odds ratio (95% CI) is 0.924(0.885 to 0.964).

Fig. 87A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation lowest initial anterior wall impedance, while fig. 87B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation lowest initial anterior wall impedance in studies of the present disclosure. It can be seen that in the optimal range of about 80 Ω to 90 Ω, the single freeze isolation rate is almost approximately between 85.7% to 87.5%. The P value of fig. 87B was 0.005 and the odds ratio (95% CI) was 0.940(0.898 to 0.983).

Fig. 88A shows a bar graph summarizing single freeze isolation probability versus pre-ablation highest initial anterior wall impedance, while fig. 88B shows a binary fit line graph of single freeze isolation probability versus pre-ablation highest initial anterior wall impedance in studies of the present disclosure. It can be seen that in the optimal range of about 110 Ω, the single freeze isolation rate is almost approximately between 88.9% and 96.9%. The P value of fig. 67B was 0.000, and the odds ratio (95% CI) was 0.950(0.926 to 0.974).

Fig. 89A shows a bar graph summarizing single freeze isolation probability versus pre-ablation initial anterior wall impedance change, while fig. 89B shows a binary fit line graph of single freeze isolation probability versus pre-ablation initial anterior wall impedance change in studies of the present disclosure. It can be seen that in the range of less than about 20 Ω, the single freeze isolation rate is almost approximately between 87.5% and 89.5%. The P value of FIG. 89B was 0.003 and the odds ratio (95% CI) was 0.962(0.936 to 0.988).

Figure 90A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation average temperature slopes, while figure 90B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation average temperature slopes in studies of the present disclosure. The P value of FIG. 90B is 0.003 and the odds ratio (95% CI) is 6.145(1.754 to 21.529).

Fig. 91A shows a bar graph summarizing single freeze isolation probability versus pre-ablation minimum temperature slope, while fig. 91B shows a binary fit line graph of single freeze isolation probability versus pre-ablation minimum temperature slope in studies of the present disclosure. It can be seen that in the range of greater than or equal to about 0.75 deg.C/s, the single freeze isolation rate is greater than about 90%. The P value of FIG. 91B was 0.001 and the odds ratio (95% CI) was 7.251(2.023 to 25.983).

Fig. 92A shows a bar graph summarizing single-pass cryoisolation probability versus pre-ablation maximum temperature slope, while fig. 92B shows a binary fit line graph of single-pass cryoisolation probability versus pre-ablation maximum temperature slope in studies of the present disclosure. The P value of fig. 92B is 0.129 and the odds ratio (95% CI) is 1.614(0.860 to 3.029).

Fig. 93A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation temperature slope changes, while fig. 93B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation temperature slope changes in studies of the present disclosure. The P value of fig. 93B was 0.837, and the odds ratio (95% CI) was 0.943(0.541 to 1.644).

Fig. 94A shows a bar graph summarizing single freeze isolation probability versus pre-ablation average temperature rise, while fig. 94B shows a binary fit line graph of single freeze isolation probability versus pre-ablation average temperature rise in studies of the present disclosure. It can be seen that for average temperature increases equal to or greater than about 14 ℃, the single freeze isolation rate is greater than about 90%. The P value of fig. 94B was 0.003 and the odds ratio (95% CI) was 1.170(1.050 to 1.304).

Fig. 95A shows a bar graph summarizing single freeze isolation probability versus pre-ablation minimum temperature rise, while fig. 95B shows a binary fit line graph of single freeze isolation probability versus pre-ablation minimum temperature rise in studies of the present disclosure. It can be seen that for the lowest temperature rise of equal to or greater than about 6 ℃, the single freeze isolation rate is greater than about 90%. The P value of fig. 95B is 0.000 and the odds ratio (95% CI) is 1.320(1.122 to 1.553).

Fig. 96A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation maximum temperature rise, while fig. 96B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation maximum temperature rise in studies of the present disclosure. The P value of FIG. 96B was 0.126, and the odds ratio (95% CI) was 1.053(0.985 to 1.125).

Fig. 97A shows a bar graph summarizing single freeze isolation probability versus pre-ablation temperature rise change, while fig. 97B shows a binary fit line graph of single freeze isolation probability versus pre-ablation temperature rise change in studies of the present disclosure. The P value of FIG. 97B is 0.546 and the odds ratio (95% CI) is 0.979(0.914 to 1.049).

Fig. 98A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation maximum average temperatures, while fig. 98B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation maximum average temperatures in studies of the present disclosure. The P value of fig. 98B was 0.010 and the odds ratio (95% CI) was 1.189(1.039 to 1.359).

Fig. 99A shows a bar graph summarizing single-pass freeze isolation probabilities versus pre-ablation minimum maximum temperatures, while fig. 99B shows a binary fit line graph of single-pass freeze isolation probabilities versus pre-ablation minimum maximum temperatures in studies of the present disclosure. The P value of fig. 99B was 0.022, and the odds ratio (95% CI) was 1.250(1.022 to 1.528).

Graph 100A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation maximum temperature, while graph 100B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation maximum temperature in studies of the present disclosure. The P value of graph 100B is 0.162 and the odds ratio (95% CI) is 1.050(0.980 to 1.125).

Fig. 101A shows a bar graph summarizing single freeze isolation probability versus pre-ablation maximum temperature change, while fig. 101B shows a binary fit line graph of single freeze isolation probability versus pre-ablation maximum temperature change in studies of the present disclosure. The P value of FIG. 101B is 0.576 and the odds ratio (95% CI) is 1.021(0.950 to 1.097).

Fig. 102A shows a bar graph summarizing single freeze isolation probability versus pre-ablation mean impedance drop, while fig. 102B shows a binary fit line graph of single freeze isolation probability versus pre-ablation mean impedance drop in studies of the present disclosure. The P value of graph 102B is 0.805 and the odds ratio (95% CI) is 1.008(0.944 to 1.077).

Fig. 103A shows a bar graph summarizing single freeze isolation probability versus pre-ablation lowest value impedance drop, while fig. 103B shows a binary fit line graph of single freeze isolation probability versus pre-ablation lowest value impedance drop in studies of the present disclosure. It can be seen that the single freeze isolation rate is greater than about 90% when the impedance drop is in the range of approximately greater than or equal to about 12 Ω. The P value of FIG. 103B is 0.000 and the odds ratio (95% CI) is 1.146(1.057 to 1.243).

Fig. 104A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation maximum impedance drops, while fig. 104B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation maximum impedance drops in studies of the present disclosure. The P value of fig. 104B was 0.022, and the odds ratio (95% CI) was 0.964(0.934 to 0.995).

Fig. 105A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation impedance drop changes, while fig. 105B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation impedance drop changes in studies of the present disclosure. It can be seen that the single pass freeze isolation rate is greater than about 85% when the impedance drop variation is in the range of approximately less than about 20 Ω. The P value of fig. 105B was 0.000 and the odds ratio (95% CI) was 0.941(0.911 to 0.972).

Fig. 106A shows a bar graph summarizing single freeze isolation probabilities versus percentage of lowest value impedance drop before ablation, while fig. 106B shows a binary fit line graph of single freeze isolation probabilities versus percentage of lowest value impedance drop before ablation in studies of the present disclosure. It can be seen that the single pass freeze isolation rate is greater than about 90% when the percent minimum impedance drop is in the range of approximately greater than or equal to about 12%. The P value of fig. 106B was 0.000 and the odds ratio (95% CI) was 1.166(1.077 to 1.263).

Fig. 107A shows a bar graph summarizing single freeze isolation probability versus pre-ablation impedance percent decrease change, while fig. 107B shows a binary fit line graph of single freeze isolation probability versus pre-ablation impedance percent decrease change in studies of the present disclosure. It can be seen that the single freeze isolation rate is greater than about 85% when the impedance drop variation is in the range of less than 20 Ω. The P value of FIG. 107B was 0.004, and the odds ratio (95% CI) was 0.931(0.887 to 0.978).

Fig. 108A shows a bar graph summarizing single freeze isolation probabilities versus pre-ablation initial impedance deviations from mean, while fig. 108B shows a binary fit line graph of single freeze isolation probabilities versus pre-ablation initial impedance deviations from mean in studies of the present disclosure. It can be seen that the single freeze isolation rate is approximately about 92.3% (n is about 13) when the number of electrodes having initial impedance deviations from the mean is zero. The P value of fig. 108B was 0.009, and the odds ratio (95% CI) was 0.821(0.708 to 0.953).

Fig. 109 shows a table summarizing predictors associated with corresponding pearson-related values and binary logistic regression values in studies of the present disclosure. Specifically, the table shows that, among the ten electrodes, the predictors studied included: (a) a number of electrodes having an initial impedance that is at least 10 Ω above the average, (b) a number of electrodes having an initial impedance that is at least 10 Ω below the average, and (c) a number of electrodes having an initial impedance that is at least 10 Ω above or below the average.

Fig. 110 shows a table summarizing pre-ablation and post-ablation parameters for the studies of the present disclosure with respect to impedance, change in impedance, lowest initial impedance, average initial impedance, change in initial impedance, lowest maximum temperature, lowest impedance drop, average impedance drop, and change in impedance drop. Excluding enrolled cases in the SHINE clinical study, there were 95 cases (including 8 enrolled cases), and only the first freeze using full circumference (e.g., full electrode burn) and full duration (e.g., 60 seconds) per PV was evaluated for analysis (using Minitab tool), including a total of 211 ablations using 156 single cryoisolations (excluding the left common pulmonary vein ("LCPV") and the right middle pulmonary vein ("RMPV")). Each parameter, which is a potential predictor of single freeze isolation (including LCPV and RMPV), was evaluated using Minitabe pearson correlation and a binary logistic regression model. It should be understood that the larger the coefficients of the table in graph 110 and the lower the P value, the better the predictor. In this analysis, the pre-ablation parameters mean initial impedance and initial impedance change were considered predictors of single cryoisolation, similar to fig. 109. With respect to post-ablation parameters, the lowest impedance drop and the change in impedance drop were similarly considered predictors of single cryoisolation, also similar to fig. 109.

Figure 111 shows a binary fit line plot of single freeze isolation probability versus pre-ablation lowest anterior impedance in a study of the present disclosure. Fig. 112 shows a binary fit line plot of single cryo-isolation probability versus pre-ablation impedance change in studies of the present disclosure. Fig. 113 shows a binary fit line plot of single cryo-isolation probability versus pre-ablation lowest impedance in a study of the present disclosure. Figure 114 shows a binary fit line plot of single freeze isolation probability versus pre-ablation mean impedance in a study of the present disclosure. Figure 115 shows a binary fit line plot of single freeze isolation probability versus pre-ablation impedance change in the study of the present disclosure. Figure 116 shows a binary fit line plot of single freeze isolation probability versus lowest maximum temperature after ablation in a study of the present disclosure. Figure 117 shows a binary fit line plot of single freeze isolation probability versus minimum impedance drop after ablation in a study of the present disclosure. Figure 118 shows a binary fit line plot of single freeze isolation probability versus post-ablation mean impedance drop in studies of the present disclosure. Figure 119 shows a binary fit line plot of single freeze isolation probability versus post-ablation impedance drop change in the study of the present disclosure.

Figure 120A shows a plot summarizing single freeze electrode temperature versus time for electrodes of balloon catheters used in studies of the present disclosure, while figure 120B shows a plot summarizing single freeze electrode impedance versus time for electrodes of balloon catheters used in studies of the present disclosure. Fig. 121 shows a table summarizing impedance values and temperature values from the graphs of fig. 120A to 120B. In the aggregated exemplary data, a balloon catheter was placed at the lesion site and initial temperature and impedance measurements were taken to determine predictors of PVI success rate.

It is observed that the initial temperature values of the graphs 120A-120B have relatively low values with a relatively narrow range determined to be a more desirable PVI success rate predictor than the absolute value of the temperature readings within a predetermined range. The absolute temperature of the electrodes of the balloon catheter analyzed depends on tissue touch, blood temperature, and/or perfusion temperature. Generally, it is observed that temperature is less affected by the patient and tissue type, and is generally unaffected by radio frequency generated artifacts.

In the graphs 120A-120B, it is also observed that the initial impedance value having a relatively high value with a relatively narrow range is effective as a predictor of PVI success rate, more effectively than the absolute value of the impedance reading is within a predetermined range. The absolute impedance may depend on the patient, the tissue type, and the degree of contact, and in general, the impedance may be affected by radio frequency generated artifacts (e.g., interference, calibration, leakage). In some examples, the extreme impedance drop may be a predictor of poor contact.

Fig. 122 shows a table demonstrating temperature and impedance trends in the electrodes of a balloon catheter in relation to a single freeze versus no isolation comparison for the cases of the study of the present disclosure. By monitoring the temperature of the balloon catheter before and during ablation, PVI success can be predicted. It was observed that the information summarized in this table is particularly useful in predicting PVI success by using temperature and impedance in tandem before and/or during ablation, as both parameters can provide feedback in a complementary manner.

Fig. 123A shows a graph summarizing electrode temperature versus time in a study of the present disclosure, while fig. 123B shows a graph summarizing electrode impedance versus time in a study of the present disclosure. Fig. 124 shows a graph summarizing electrode impedance phase versus time in a study of the present disclosure.

During the ablation of fig. 123B-124, measurements of temperature and impedance may be taken to provide an indication of the ultimate success of the ablation procedure. The impedance drop was expected, and the impedance drops of fig. 123B-124 were observed to be similar and significant for each electrode. Observing the data of fig. 123B-124, the use of temperature, impedance, and/or impedance phase change parameters during ablation is an indicator of PVI success rate when using the balloon catheter of the present disclosure.

Fig. 125 depicts a method or use 12500 for treating paroxysmal atrial fibrillation in a predetermined patient population. The method or use 12510 may include ablating one or more pulmonary vein-targeted tissues with one or more of a plurality of electrodes of an independently controlled multi-electrode radio frequency balloon catheter, the balloon catheter including a plurality of electrodes for radio frequency ablation that are independently controllable; 12520 determining a characteristic of single-freeze Pulmonary Vein Isolation (PVI) success rate based on ablation parameters of the balloon catheter; 12530 based on this characteristic and the ablation tissue step, a single cryo-isolation PVI success rate is achieved in isolation of all targeted pulmonary veins of the predetermined patient population; and 12540 electrodes that display this characteristic and that are energized during ablation.

Fig. 126 depicts a method or use 12600 for treating paroxysmal atrial fibrillation in a predetermined patient population. The method or use 12610 may include ablating one or more pulmonary vein-targeted tissues with one or more of a plurality of electrodes of an independently controlled multi-electrode radio frequency balloon catheter comprising a plurality of electrodes for radio frequency ablation that are independently controllable; 12620 determine a characteristic of single-freeze Pulmonary Vein Isolation (PVI) success rate based on ablation parameters of the balloon catheter; and 12630, based on the characteristics and the ablating tissue step, a single cryo-isolation PVI success rate is achieved in all targeted pulmonary vein isolations of the predetermined patient population. The method or use may include 12640 displaying the characteristic and an identification of an electrode energized during ablation. Additionally, or optionally, the characteristics (e.g., predictor or evaluator factors) and the identity of the electrodes energized during ablation are graphically represented in a graphical display, such as that shown in fig. 128.

FIG. 127 illustrates an exemplary flow diagram of a subroutine for determining a probability of success from a single parameter predictor/evaluator (Table 1) or a multi-parameter predictor/evaluator (Table 2). The subroutine begins at step 1270, whereupon the processor initiates a low current signal that will be sent from the generator to each of the ten electrodes and body patches (also referred to as indifferent electrodes). At step 1272, the processor also collects temperature measurements from thermocouples or temperature sensors proximate each electrode. In step 1274, the temperature values are recorded into the memory of the processor for analysis. The processor retrieves the measured temperature values and derives (a) an initial temperature change Δ T ₀(ii) a (b) Maximum initial temperature T_0max(ii) a (c) Minimum temperature rise delta T_min. At step 1282, the processor retrieves the impedance measurements of the data record and derives (a) an initial impedance change Δ Z₀(ii) a (b) Highest initial impedance Z_0max(ii) a (c) Mean initial impedance Z_0mean(ii) a (d) Change in impedance drop Δ Z_drop(ii) a (e) Lowest impedance drop Z_dropmin(ii) a (f) Percent change in impedance drop Δ Z_dropPercent; and (g) percent decrease in minimum impedance Z_drop％_min。

If ablation is not complete at step 1284, the processor continues to collect temperature values and impedance values in steps 1272 through 1282. On the other hand, if the first ablation has been completed, the decision moves to step 1286, which refers to a look-up table (e.g., table 1) that is used to determine the probability of success using a single parameter (temperature or impedance) in step 1288. The processor moves to step 1290 to calculate a probability of success using more than a single parameter based on the data from the SHINE study. The processor may use one or more of the Y terms derived in data store 1290 for the formula in step 1292. At step 1294, either the single parameter success probability in step 1288 or the multi-parameter success probability in step 1292 is output. The system can display both the single parameter probability of step 1288 and the multi-parameter probability of success of step 1292 in the form of cross-check accuracy.

An exemplary graphical user interface and display 1300 is reflected in fig. 128. GUI display 1300 provides summary information or statistics of the electrode ablation procedure that the physician may find useful in determining further therapies. As shown, the electrode icon 1320 is highlighted so that the information provided corresponds to the first electrode. A visual indicator 1322 of the probability of success P may be provided on the GUI display 1300 either before the actual ablation or also after the ablation. Visual indicator 1322 may be provided before, during, or after the first ablation for consideration by the physician as to whether to proceed with one or more subsequent ablations. Subsequent ablation is sometimes required to ensure that all tissue generating the erratic signal is completely ablated, and any non-ablated or partially ablated tissue will not form a re-connection that propagates the erratic rhythm signal. By giving such an indication to the physician (where indicator 1322 is one example), the physician may decide whether the first ablation is sufficient or whether to continue with a subsequent ablation.

The following clauses set forth non-limiting embodiments of the present disclosure:

1. a method or use of treating paroxysmal atrial fibrillation in a predetermined patient population, the method or use comprising:

Ablating one or more pulmonary vein-targeted tissues using one or more of a plurality of electrodes of an independently controlled multi-electrode radio frequency balloon catheter, the balloon catheter comprising a plurality of electrodes for radio frequency ablation that are independently controllable;

determining a characteristic of single-freeze Pulmonary Vein Isolation (PVI) success rate based on an ablation parameter of a balloon catheter; and

based on this characteristic and the ablation tissue step, a single cryo-isolation PVI success rate is achieved in all targeted pulmonary vein isolations of the predetermined patient population.

2. The method or use of clause 1, wherein the step of achieving single-pass cryo-isolation PVI success rate further comprises further ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes based on the characteristic.

3. The method or use of clause 1, wherein the step of achieving a single cryo-isolated PVI success rate further comprises ceasing further ablation of tissue with the multi-electrode radio frequency balloon catheter based on the characteristic.

4. The method or use of clause 1, wherein the step of achieving a single freeze isolated PVI success rate further comprises achieving a success rate of at least about 91.7% by ablating with a pre-ablation average initial impedance of less than about 95 Ω.

5. The method or use of clause 1, wherein the step of achieving a single freeze isolated PVI success rate further comprises achieving a success rate of at least about 91.7% by ablating with a highest pre-ablation initial impedance of less than about 100 Ω.

6. The method or use of clause 1, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 87% by ablating with a pre-ablation initial anterior wall impedance of less than about 95 Ω.

7. The method or use of clause 1, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 85% by ablating with a pre-ablation minimum initial anterior wall impedance of between about 80 Ω to 90 Ω.

8. The method or use of clause 1, wherein the step of achieving a single freeze isolated PVI success rate further comprises achieving a success rate of at least about 88% by ablating with a pre-ablation highest initial anterior wall impedance of about 110 Ω.

9. The method or use of clause 1, wherein the step of achieving a single freeze-isolated PVI success rate further comprises achieving a success rate of at least about 87.5% by ablating with a pre-ablation initial anterior wall impedance change impedance range of less than about 20 Ω.

10. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor limiting a maximum initial temperature among the electrodes of the balloon catheter to less than about 31 ℃.

11. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor allowing for a lowest anterior wall impedance approximately between about 80 Ω to 90 Ω.

12. The method or use of clause 1, wherein the step of achieving a single freeze isolated PVI success rate further comprises achieving a success rate of at least about 90% by ablating with a mean initial impedance of less than about 95 Ω and a highest initial impedance of less than about 110 Ω.

13. The method or use according to clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being initial temperature and initial impedance at the lesion site immediately prior to the ablation step.

14. The method or use according to clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being a relatively low initial temperature and initial impedance at the lesion site immediately prior to the ablation step.

15. The method or use according to clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being initial impedance at the lesion site and initial temperature in a relatively low range immediately prior to the ablation step.

16. The method or use according to clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being an initial impedance having a relatively high value in a relatively narrow range.

17. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being an absolute value of an impedance reading within a predetermined range.

18. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate before and during ablation, the predictor being electrode temperature before and during ablation.

19. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a mean initial temperature, and wherein the mean initial temperature is approximately less than about 28 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

20. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed onset temperature, and wherein the distributed onset temperature is approximately greater than about 31 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

21. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed onset temperature, and wherein the distributed onset temperature is approximately greater than about 30 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

22. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed onset temperature, and wherein the distributed onset temperature is approximately greater than about 29 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

23. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature slope, and wherein the pre-ablation minimum temperature slope is approximately greater than about 0.75 ℃/s, and the single freeze isolated PVI success rate is approximately at least about 90%.

24. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature, and wherein the pre-ablation minimum temperature is approximately greater than about 6 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

25. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation maximum initial temperature, and wherein the pre-ablation maximum initial temperature is approximately less than about 31 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

26. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation initial temperature variation, and wherein the pre-ablation initial temperature variation is approximately less than about 3 ℃, and the single freeze isolated PVI success rate is approximately at least about 95%.

27. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation initial impedance variation, and wherein the pre-ablation initial impedance variation comprises an optimal range of approximately less than about 20 Ω, and the single freeze isolation PVI success rate is approximately at least about 88.5%.

28. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation minimum impedance dip, and wherein the pre-ablation minimum impedance dip is approximately greater than about 12 Ω, and the single freeze isolation PVI success rate is approximately at least about 90%.

29. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being pre-ablation impedance drop variation, and wherein the pre-ablation impedance drop variation is approximately greater than about 20 Ω and the single freeze isolation PVI success rate is approximately at least about 85%.

30. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation minimum impedance reduction percentage, and wherein the pre-ablation minimum impedance reduction percentage is approximately greater than or equal to about 12%, and the single freeze isolation PVI success rate is approximately at least about 90%.

31. The method or use of clause 1, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation impedance reduction percentage change, and wherein the pre-ablation impedance reduction percentage change is less than about 20 Ω, and the single freeze isolation PVI success rate is approximately at least about 85%.

32. The method or use of clause 1, wherein the single freeze isolated PVI success rate is approximately about 92% when the number of electrodes having an initial impedance deviation from the average is zero.

33. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being the difference in impedance between the anterior and posterior walls.

34. The method or use of clause 33, wherein the difference is approximately less than about 20 Ω for the predetermined patient population and the single freeze PVI success rate is approximately at least about 85%.

35. The method or use of clause 33, wherein the difference is approximately less than about 20 Ω for a predetermined patient population of at least 25 patients, and the single freeze PVI success rate is approximately at least about 85%.

36. The method or use of clause 33, wherein the difference is approximately between 20 Ω to 30 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 78%.

37. The method or use of clause 33, wherein the difference is approximately between 20 Ω to 30 Ω and the single freeze PVI success rate is approximately at least about 78% for a predetermined patient population of at least 75 patients.

38. The method or use of clause 33, wherein the difference is approximately between 30 Ω to 40 Ω and the single freeze PVI success rate is approximately at least about 75% for the predetermined patient population.

39. The method or use of clause 33, wherein the difference is approximately between 30 Ω to 40 Ω and the single freeze PVI success rate is approximately at least about 75% for a predetermined patient population of at least 60 patients.

40. The method or use of clause 33, wherein the difference is approximately between 40 Ω to 50 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 67%.

41. The method or use of clause 33, wherein the difference is approximately between 40 Ω to 50 Ω for a predetermined patient population of at least 34 patients, and the single freeze PVI success rate is approximately at least about 67%.

42. The method or use of clause 33, wherein the difference is approximately between 50 Ω to 60 Ω and the single freeze PVI success rate is approximately at least about 35% for the predetermined patient population.

43. The method or use of clause 33, wherein the difference is approximately between 50 Ω to 60 Ω and the single freeze PVI success rate is approximately at least about 35% for a predetermined patient population of at least 11 patients.

44. The method or use of clause 33, wherein the difference is approximately greater than about 60 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 33%.

45. The method or use of clause 33, wherein the difference is approximately greater than about 60 Ω and the single-freeze PVI success rate is approximately at least about 33% for a predetermined patient population of at least 9 patients.

46. The method or use of clause 33, wherein the balloon catheter is a full circumferential full electrode combustion ablation catheter.

47. The method or use of clause 33, wherein the step of ablating the tissue lasts for 60 seconds.

48. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation average initial impedance is the predictor.

49. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation initial impedance change is the predictor.

50. The method or use according to clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the minimum impedance after ablation falls to the assessment factor.

51. The method or use according to clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation impedance drop changes to the assessment factor.

52. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein post-ablation average temperature slope is the evaluation factor.

53. The method or use of clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the minimum temperature slope after ablation is a predictor.

54. The method or use according to clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation average temperature rise is the assessment factor.

55. The method or use of clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation coldest temperature rises to the assessment factor.

56. The method or use of clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the percentage of minimum impedance drop after ablation is the assessment factor.

57. The method or use according to clause 1, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the percentage of impedance drop after ablation varies as the assessment factor.

58. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation minimum impedance falls to the predictor.

59. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation initial temperature change is the predictor.

60. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation maximum initial impedance is the predictor.

61. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation average initial anterior wall impedance is the predictor.

62. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation minimum anterior wall impedance is the predictor.

63. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation maximum anterior wall impedance is the predictor.

64. The method or use of clause 1, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation anterior wall impedance changes to the predictor.

65. The method or use of any preceding clause, wherein the impedance value is an impedance value among the electrodes of the front wall.

66. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～4.367-0.420ΔT₀-0.0486ΔZ₀

wherein Δ T₀Is the initial impedance change and Δ Z₀Is the initial temperature change.

67. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～26.78-0.576T_0max-0.0632Z_0max

wherein T is_0maxIs the maximum initial temperature and Z_0maxThe highest initial impedance.

68. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～27.70-0.540T_0max-0.0959Z_0max

Wherein T is_0maxIs the maximum initial temperature and Z_0maxThe highest initial impedance.

69. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～9.31-0.408ΔT₀-0.0544Z_0max

wherein Δ T₀Is an initial temperature change and Z_0maxThe highest initial impedance.

70. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～22.61-0.622T_0max-0.0626ΔZ₀

wherein T is_0maxIs the maximum initial temperature and Δ Z₀Is the initial impedance change.

71. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～11.53-0.439ΔT₀-0.0856Z_0mean

wherein Δ T₀Is an initial temperature change and Z_0meanIs the average initial impedance.

72. The method or use according to any preceding clause, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～26.52+0.013ΔT₀-0.594T_0max-0.0122ΔZ₀-0.0535Z_0max

wherein Δ T₀For initial temperature change, T _0maxAt the maximum initial temperature,. DELTA.Z₀Is an initial impedance change, and Z_0maxThe highest initial impedance.

73. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.562+0.2856ΔT_min-0.0629ΔZ_drop

wherein Δ T_minIs the lowest temperature rise and Δ Z_dropIs the impedance drop change.

74. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～-0.507+0.206ΔT_min+0.083Z_dropmin

wherein Δ T_minIs the lowest temperature rise and Z_dropminThe minimum impedance drop.

75. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.248+0.2486ΔT_min-0.0594ΔZ_drop+0.0419Z_dropmin

wherein Δ T_minIs the lowest temperature rise and Z_dropminThe minimum impedance drop.

76. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.174+0.2515ΔT_min-0.0564ΔZ_drop％

wherein Δ T_minIs the lowest temperature rise and Δ Z _dropIs the percent change in impedance drop.

77. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～-0.644+0.170ΔT_min+0.107Z_drop％_min

wherein Δ T_minIs the lowest temperature rise and Z_drop％_minIs the lowest percent impedance drop.

78. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～0.339+0.187ΔT_min+0.0737Z_drop％_min-0.0368ΔZ_drop％

wherein Δ T_minAt the lowest temperature rise, Z_drop％_minIs the minimum percent resistance reduction, an

ΔZ_drop% is the percent change in impedance drop.

79. The method or use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.043+0.777T′_min+0.171ΔT_min+0.0479Z_drop-min-0.0589ΔZ_drop

wherein T'_minIs the lowest temperature slope, Δ T_minAt the lowest temperature rise, Z_drop-minIs the lowest impedance drop, and Δ Z_dropIs the impedance drop change.

80. The method or use according to claim 1, further comprising the step of displaying a graphical representation of the independently controllable electrodes and ablation parameters.

81. The method or use of clause 74, wherein the one ablation parameter comprises an impedance measured proximate each electrode.

82. The method or use of clause 75, wherein the measured impedance comprises an impedance measured prior to ablation.

83. The method or use of clause 75, wherein the measured impedance comprises an impedance measured after ablation.

84. The method or use of clause 75, wherein the measured impedance comprises an impedance measured before ablation and an impedance measured after ablation.

85. The method or use of clause 74, wherein the one ablation parameter comprises a temperature measured proximate each electrode.

86. The method or use of clause 74, wherein the one ablation parameter comprises a maximum temperature measured proximate each electrode during ablation.

87. The method or use of clause 74, wherein one ablation parameter comprises a temperature rise measured from the start of ablation to the end of ablation.

88. A method or use for treating paroxysmal atrial fibrillation in a plurality of patients, the method or use comprising the steps of:

delivering a multi-electrode diagnostic catheter and a multi-electrode radiofrequency balloon catheter having a plurality of individually controllable electrodes for radiofrequency ablation to one or more targeted pulmonary veins;

ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter;

Diagnosing one or more targeted pulmonary veins using a multi-electrode diagnostic catheter; and

at least one of a predetermined clinical effectiveness and an acute effectiveness of the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter is achieved in the isolation of the one or more targeted pulmonary veins during and approximately 3 months after the ablating step.

89. The method or use of clause 82, wherein acute efficacy is defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge.

90. The method or use of clause 83, further comprising: determining the acute effectiveness determined at about 3 months after the ablating step; and

based on the acute effectiveness determined at about 3 months, an estimated acute effectiveness is generated at about 12 months after the ablation step.

91. The method or use of clause 84, wherein the estimated acute effectiveness at about 12 months is substantially similar to the acute effectiveness determined at about 3 months.

92. The method or use of clause 83, wherein acute effectiveness is further defined by a success rate of greater than 90% for the plurality of patients.

93. The method or use of clause 83, wherein acute effectiveness is further defined by a success rate of greater than 95% for the plurality of patients.

94. The method or use of clause 83, wherein the confidence of acute and clinical effectiveness of all targeted veins type 1 error rates are controlled at a level of about 5%, the method or use further comprising:

if both the acute and clinical effectiveness indicators are controlled at a level of about 5%, then it is determined whether ablation is clinically successful for a plurality of patients.

95. The method or use of clause 83, wherein the acute effectiveness is at least 80% for a plurality of at least 80 patients.

96. The method or use of clause 83, wherein the acute effectiveness is at least 80% for a plurality of at least 130 patients.

97. The method or use of clause 83, wherein the acute effectiveness is at least 80% for a plurality of at least 180 patients.

98. The method or use of clause 83, wherein the acute effectiveness is at least 80% for a plurality of at least 230 patients.

99. The method or use of clause 83, wherein acute efficacy is further defined by confirming whether there is an entry block in all targeted pulmonary veins with the use of a focal ablation catheter after an adenosine and/or isoproterenol challenge.

100. The method or use of clause 83, wherein acute efficacy is further defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge without the use of a focal ablation catheter.

101. The method or use of clause 82, wherein the ablation is administered to a plurality of patients diagnosed with symptomatic paroxysmal atrial fibrillation.

102. The method or use of clause 82, wherein the diagnosing step further comprises:

electrophysiological mapping of the heart.

103. The method or use of clause 82, wherein the multi-electrode diagnostic catheter further comprises a high torque shaft having a halo-shaped tip section comprising a plurality of pairs of electrodes visible under fluoroscopy.

104. The method or use of clause 82, wherein the plurality of patients is at least 80.

105. The method or use of clause 82, wherein the plurality of patients is at least 130.

106. The method or use of clause 82, wherein the plurality of patients is at least 180.

107. The method or use of clause 82, wherein the plurality of patients is at least 230.

108. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by the absence of an ulcer in the plurality of patients after ablation.

109. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a complication rate of about 13% or less of esophageal erythema experienced by a plurality of patients after ablation.

110. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a complication rate of about 25% or less of a plurality of patients experiencing a new asymptomatic thromboembolic lesion after ablation.

111. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a complication rate of about 20% or less of a plurality of patients experiencing a new asymptomatic thromboembolic lesion after ablation.

112. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a complication rate of about 5% to 9% or less of the plurality of patients experiencing the primary adverse event about 7 days or more after ablation.

113. The method or use of clause 82, wherein the inclusion criteria for the plurality of patients comprises:

diagnosed as having symptomatic paroxysmal atrial fibrillation; and

the patient is able to comply with the ongoing on-schedule anticoagulation requirements.

114. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a total protocol time.

115. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a total ablation time.

116. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a total radio frequency application time.

117. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by a total dwell time of the multi-electrode radiofrequency balloon catheter.

118. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by the total time to isolate all targeted pulmonary veins.

119. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radiofrequency balloon catheter at each location of all targeted pulmonary veins.

120. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radiofrequency balloon catheter to each patient.

121. The method or use of clause 82, wherein the predetermined acute effectiveness is defined by the number of applications and total time of application of the multi-electrode radio frequency balloon catheter to each targeted vein.

122. The method or use of any preceding clause, wherein the multi-electrode radiofrequency balloon catheter comprises:

A compliant balloon incorporating a plurality of electrodes configured to deliver radio frequency energy to tissue of a pulmonary vein and sense a temperature at each electrode.

123. The method or use of clause 82, wherein clinical effectiveness is defined by the incidence of early onset of one or more adverse events within a predetermined time of the method or use being performed.

124. The method or use of clause 117, wherein the predetermined time is at least 7 days.

125. The method or use of clause 117, wherein the one or more adverse events comprise: death, atrioesophageal fistula, myocardial infarction, cardiac packing/perforation, thromboembolism, stroke, TIA (transient ischemic attack), phrenic nerve paralysis, pulmonary vein stenosis and large vessel access bleeding.

126. The method or use of clause 117, wherein the one or more adverse events comprise: the incidence of individual adverse events from the primary composite event; the incidence of serious adverse device effects; incidence of severe adverse events within 7 days, at least 7 days to 30 days, and at least 30 days post ablation; the incidence of non-serious adverse events; the incidence of asymptomatic and symptomatic cerebral embolism as determined by MRI assessment before and after ablation; and the frequency, anatomical location and size (diameter and volume) of cerebral emboli assessed by MRI at baseline, post-ablation and during follow-up.

127. The method or use of clause 117, wherein about 5% to 9% of the plurality of patients develop one or more adverse events comprising:

NIHSS (national institute of health stroke scale) scores at baseline, post-ablation, and during follow-up;

a summary of MoCA (montreal cognitive assessment) scores and mRS (modified Rankin scale) scores at baseline, 1 month, and during further follow-up; the hospitalization rate for cardiovascular events; percentage (%) of pulmonary vein isolation supplemental ablation by focal catheter among the one or more targeted veins;

percent (%) of subjects with non-PV triggering using focal catheter ablation;

(ii) percentage (%) of subjects with no recorded symptomatic Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left side) Atrial Flutter (AFL) episodes (> 30 seconds of episodes from day 91 to day 180 on arrhythmia monitoring device);

percent (%) of subjects with no recorded Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left-sided) Atrial Flutter (AFL);

one or more episodes lasting 30 seconds or more on the arrhythmia monitoring device from day 91 to day 180 after ablation; and

One or more protocol parameters including total protocol and ablation time, balloon dwell time, radio frequency application times, fluoroscopy time and dose.

128. The method or use of clause 82, wherein the acute safety rate comprises a complication rate of 10% or less and is defined by the incidence of asymptomatic cerebral embolic lesions upon discharge electromagnetic resonance imaging (MRI).

129. The method or use of clause 82, wherein the acute effective rate is 100% and is defined by electrically isolating all targeted pulmonary veins without the use of a focal ablation catheter.

130. The method or use of clause 82, wherein acute effective rate is defined by determining no recorded atrial fibrillation, atrial tachycardia or atypical atrial flutter episode based on electrocardiographic data over an entire validity assessment period (1 year).

131. The method or use of clause 82, wherein acute effective rate is defined by pulmonary vein isolation supplemental ablation of the focal catheter among all targeted pulmonary veins.

132. The method or use of clause 82, wherein the predetermined clinical effectiveness rate is defined by a complication incidence of 10% or less associated with the incidence of symptomatic and asymptomatic cerebral embolism after ablation as compared to before ablation.

133. The method or use of clause 82, wherein the multi-electrode diagnostic catheter is configured for electrophysiological recording and stimulation of an atrial region of the heart and is used in conjunction with the multi-electrode radiofrequency balloon catheter.

134. A method or use for treating paroxysmal atrial fibrillation in a plurality of patients, the method or use comprising the steps of:

delivering a multi-electrode diagnostic catheter and a multi-electrode radiofrequency balloon catheter having a plurality of individually controllable electrodes for radiofrequency ablation to one or more targeted pulmonary veins; and

ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter;

diagnosing all targeted pulmonary veins using a multi-electrode diagnostic catheter; and

during and approximately 6 months after the method or use, a predetermined adverse event rate based on the use of the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter in isolation of all targeted pulmonary veins is achieved.

135. A method or use for treating paroxysmal atrial fibrillation in a plurality of patients, the method or use comprising the steps of:

assessing the number and size of all targeted pulmonary veins and anatomical structures of the left atrium;

Puncturing the transseptal space;

selectively positioning a multi-electrode esophageal temperature monitoring device in the vasculature relative to all targeted pulmonary veins;

selectively positioning a multi-electrode radio frequency balloon catheter in the vasculature relative to all targeted pulmonary veins, the multi-electrode radio frequency balloon catheter having a plurality of independently controllable electrodes for radio frequency ablation;

selectively positioning a multi-electrode diagnostic catheter in the vasculature relative to all targeted pulmonary veins;

ablating all tissue targeted to the pulmonary veins with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter;

confirming isolation of all targeted pulmonary veins using a multi-electrode diagnostic catheter;

confirming the presence of entry blockages in all targeted pulmonary veins;

based on confirming the presence of the entry block, a predetermined clinical effectiveness and/or acute effectiveness of the method or use is achieved that is associated with isolating all targeted pulmonary veins according to the method or use.

136. The method or use of any of the preceding clauses further comprising: all targeted pulmonary veins are mapped using a diagnostic catheter.

137. The method or use of any of the preceding clauses wherein the exclusion criteria for the plurality of patients comprises at least one of:

Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac causes;

previous surgical or catheter ablation for atrial fibrillation;

ablation is expected to be received outside all targeted pulmonary vein ostia and CTI regions;

previously diagnosed as having sustained, long-term atrial fibrillation and/or >7 days of continuous atrial fibrillation, or >48 hours of pre-cardioversion symptoms;

any Percutaneous Coronary Intervention (PCI) performed within the last 2 months;

valve repair or replacement and the presence of a prosthetic valve;

any carotid stenting or endarterectomy performed;

coronary artery bypass graft, heart surgery, heart valve surgery, or percutaneous surgery has been performed within the past 6 months;

left atrial thrombus recorded on baseline imaging;

the anterior-posterior diameter of the left atrium is greater than 50 mm;

the diameter of any pulmonary vein is greater than or equal to 26 mm;

left ventricular ejection fraction less than 40%;

anticoagulation contraindications;

a history of clotting or bleeding abnormalities;

myocardial infarction occurred within the past 2 months;

thromboembolic events were recorded over the past 12 months;

rheumatic heart disease;

Wait for a heart transplant or other heart surgery for the next 12 months;

unstable angina pectoris;

acute disease or active systemic infection or sepsis;

diagnosis as atrial myxoma or atrial septum or patch;

presence of implanted pacemakers, implantable cardioverter defibrillators, tissue-embedded or ferrous metal debris;

major lung disease or any other disease or dysfunction of the lung or respiratory system that produces chronic symptoms;

major congenital abnormalities;

gestation or lactation;

enrollment in an investigative study evaluating another device, biological agent or drug;

pulmonary vein stenosis;

the presence of an intramural thrombus, tumor or other abnormality that obstructs vascular access or manipulation of the catheter;

presence of an IVC filter;

presence of a disorder obstructing the vascular access;

life expectancy shorter than 12 months or with other disease processes that may limit survival to shorter than 12 months;

contraindications for the use of MRI contrast agents;

the presence of ferrous metal debris in the patient; or

Unresolved preexisting neurological deficits.

138. The method or use of any preceding clause, wherein the multi-electrode radiofrequency balloon catheter comprises:

A compliant balloon having a plurality of electrodes configured to deliver radio frequency energy to all tissue targeting the pulmonary vein and sense temperature at each electrode.

139. The method or use of clause 132, wherein the plurality of electrodes are circularly oriented to make circumferential contact with the pulmonary vein ostium.

140. The method or use of clause 132, further comprising using a plurality of electrodes for visualization, stimulation, recording, and ablation.

141. The method or use of clause 132, wherein each electrode is configured such that the amount of power delivered to each electrode is independently controlled.

142. The method or use of clause 132, wherein the multi-electrode radio frequency balloon catheter further comprises a proximal handle, a distal tip, and an intermediate section disposed between the proximal handle and the distal tip.

143. The method or use of clause 136, wherein the proximal handle is a deflection thumb knob that allows for unidirectional deflection, a balloon advancement mechanism, and a luer fitting for balloon inflation and irrigation.

144. The method or use of clause 132, wherein the multi-electrode radiofrequency balloon catheter further comprises

A high torque shaft configured for rotation to facilitate precise positioning of the catheter tip to a desired site; and

Deflectable end sections of unidirectional braid.

145. The method or use of any preceding clause, further comprising:

and (3) controlling the perfusion of the multi-electrode radio-frequency balloon catheter by using a perfusion pump.

146. The method or use of any preceding clause, further comprising:

uninterrupted anticoagulant therapy is administered at least 1 month prior to the protocol.

147. The method or use according to any preceding clause, wherein if the patient is receiving warfarin/coumarin therapy, the patient must have an International Normalized Ratio (INR) of ≧ 2 for at least 3 weeks before the procedure.

148. The method or use according to any preceding clause, wherein if the patient is receiving warfarin/coumarin therapy, it must be confirmed that the patient has an International Normalized Ratio (INR) of ≧ 2 within 48 hours prior to the procedure.

149. The method or use of any preceding clause, further comprising: anticoagulation therapy was continued prior to the protocol.

150. The method or use of any preceding clause, further comprising:

administering a transseptal puncture;

confirm an activated clotting time target of ≧ 350 seconds prior to insertion of the multi-electrode radiofrequency balloon catheter into the left atrium, and maintain the target throughout the procedure;

Introducing a multi-electrode radio frequency balloon catheter;

introducing a multi-electrode circular diagnostic catheter;

ablating pulmonary veins with a multi-electrode radio frequency balloon catheter;

determining pulmonary vein isolation in real time by using a multi-electrode circular diagnostic catheter; and

it is confirmed whether the access in the pulmonary vein is blocked.

151. The method or use of any preceding clause, wherein the multi-electrode circular diagnostic catheter comprises:

an elongated body having a longitudinal axis;

a distal assembly located distal to the elongate body, the distal assembly having a helical form comprising a proximal collar and a distal collar, the proximal and distal collars being angularly oriented relative to the longitudinal axis of the elongate body, and a shape memory support member extending at least through the proximal collar;

at least one irrigated ablation ring electrode mounted on the proximal collar;

a control handle proximal to the elongate body; and

a contraction wire having a proximal end in the control handle and a distal end anchored in the proximal collar, the control handle including a first control member configured to actuate the contraction wire to contract the proximal collar,

Wherein the proximal collar has a first flexibility and the distal collar has a second flexibility, and the second flexibility is greater than the first flexibility.

152. A method or use for treating paroxysmal atrial fibrillation in a plurality of patients by applying energy to cardiac tissue of a subject proximate the esophagus, phrenic nerve, or lung, the method or use comprising the steps of:

based on using a multi-electrode radio frequency balloon catheter and a multi-electrode diagnostic catheter in isolation of one or more targeted pulmonary veins to achieve at least one of a predetermined clinical effectiveness and acute effectiveness of a procedure by:

positioning an expandable member proximate the left atrium, the expandable member of a multi-electrode radio frequency balloon catheter having a longitudinal axis and comprising a plurality of electrodes disposed about the longitudinal axis, each electrode being independently energizable, the plurality of electrodes comprising a first electrode having a first radiopaque marking and a second electrode having a second radiopaque marking different from the first radiopaque marking;

viewing an image of the expandable member and the first and second radiopaque markings in the left atrium;

determining an orientation of the first and second radiopaque markings relative to a portion of a left atrium of the subject that is closest to an esophagus, phrenic nerve, or lung;

Moving one of the first and second radiopaque markers to a portion of the left atrium closest to the esophagus, phrenic nerve, or lung;

energizing one or more electrodes indexed proximate to one of the radiopaque markers proximate to the portion proximate to the esophagus, phrenic nerve, or lung at a lower energization setting than the other electrodes to create a transmural lesion in the left atrium with little or no effect on adjacent anatomical structures; and

electrophysiological recording and stimulation of the atrial region of tissue proximate the esophagus, phrenic nerve, or lung was performed using a multi-electrode diagnostic catheter.

153. A clinically effective apparatus for treating atrial fibrillation in a group of patients, the apparatus comprising an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion, the end probe comprising:

a first inflatable membrane coupled to the tubular member;

a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane;

at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and

A second inflatable membrane enclosing a portion of the at least one guidewire between the second inflatable membrane and the first inflatable membrane; and is

Wherein the device is configured to achieve a predetermined pulmonary vein isolation effectiveness rate in the group of patients.

154. A clinically effective apparatus for administering a protocol for performing cardiac electrophysiology ablation of atrial pulmonary veins and treatment of drug refractory relapsed symptomatic pulmonary atrial fibrillation, comprising:

an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion, the end probe comprising:

a first inflatable membrane coupled to the tubular member;

a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane;

at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and

a second inflatable membrane enclosing a portion of the at least one lead between the second inflatable membrane and the first inflatable membrane such that each electrode of the plurality of electrodes is independently controlled to achieve a predetermined effectiveness rate of pulmonary vein isolation.

155. A clinically effective apparatus for administering a protocol for performing cardiac electrophysiology ablation of atrial pulmonary veins and treatment of drug refractory relapsed symptomatic pulmonary atrial fibrillation, comprising:

an end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion, the end probe comprising:

a first inflatable membrane coupled to the tubular member;

a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane;

at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and

a second inflatable membrane encapsulating a portion of the at least one lead between the second inflatable membrane and the first inflatable membrane such that each electrode of the plurality of electrodes is independently controlled to achieve pulmonary vein isolation and a safety endpoint of at least 97% within seven (7) days of successful pulmonary vein isolation.

156. A clinically effective apparatus for administering a protocol for performing cardiac electrophysiology ablation of atrial pulmonary veins and treatment of drug refractory relapsed symptomatic pulmonary atrial fibrillation, comprising:

An end probe coupled to a tubular member extending along a longitudinal axis from a proximal portion to a distal portion, the end probe comprising:

a first inflatable membrane coupled to the tubular member;

a plurality of electrodes disposed substantially equiangularly about the longitudinal axis on the outer surface of the first inflatable membrane;

at least one lead connecting each of the plurality of electrodes, the at least one lead of each electrode extending from the first inflatable membrane toward the tubular member; and

a second inflatable membrane encapsulating a portion of the at least one lead between the second inflatable membrane and the first inflatable membrane such that each electrode of the plurality of electrodes is independently controlled to achieve pulmonary vein isolation and a safety endpoint of at least 90% within seven (7) days of successful pulmonary vein isolation.

157. The device according to one of the preceding clauses, wherein the predetermined effective rate comprises a complication rate of 10% or less and is defined by the presence or absence of an asymptomatic cerebral embolic lesion upon discharge electromagnetic resonance imaging (MRI).

158. The device according to one of the preceding clauses wherein the predetermined effective rate comprises a complication rate of about 0% and is defined by the presence or absence of esophageal injury erythema.

159. The device according to one of the preceding clauses wherein the predetermined effective rate is about 100% and is defined by electrically isolating all targeted pulmonary veins without the use of a focal ablation catheter.

160. The apparatus of one of the preceding clauses wherein the predetermined effectiveness rate is defined by determining no recorded atrial fibrillation, atrial tachycardia, or atypical atrial flutter onset based on electrocardiographic data over the entire effectiveness evaluation period.

161. The apparatus of clause 1, wherein the validity assessment period is about one year.

162. The device according to one of the preceding clauses, wherein the predetermined effective rate is defined by pulmonary vein isolation supplemental ablation of the focal catheter among all targeted pulmonary veins.

163. The apparatus according to one of the preceding clauses, wherein the predetermined effectiveness rate is defined by non-PV triggering using focal catheter ablation during an index procedure.

164. The apparatus according to one of the preceding clauses, wherein the predetermined effective rate comprises a long-term effective rate.

165. The device according to one of the preceding clauses, wherein the predetermined effective rate is defined by an average number of radiofrequency applications per patient and the radiofrequency time required to isolate all pulmonary veins.

166. The device according to one of the preceding clauses, wherein the predetermined effective rate is defined by an average number of radio frequency applications per vein and a radio frequency time required to isolate a common pulmonary vein.

167. The device according to one of the preceding clauses, wherein the predetermined effective rate is defined by an average number of radiofrequency applications per patient and a radiofrequency time required to isolate a common pulmonary vein.

168. The device according to one of the preceding clauses, wherein the predetermined effectiveness rate is defined by determining a complication rate of symptomatic and asymptomatic cerebral embolism after ablation as compared to before ablation of 10% or less.

169. The apparatus of one of the preceding clauses wherein the predetermined effective rate is defined by assessing the presence of an embolism-associated neurological deficit using at least one of a NIHSS assessment and an mRS assessment.

170. The device of any preceding clause, wherein the end probe is configured for catheter-based cardiac electrophysiology mapping of the atrium.

171. The apparatus of any preceding clause, wherein the tip probe is configured for cardiac ablation.

172. The apparatus of any preceding clause, wherein the end probe comprises: a plurality of electrodes coupled to the first inflatable membrane and configured to deliver radio frequency energy to tissue of the pulmonary vein and sense a temperature at each electrode.

173. The device of any preceding clause, wherein the plurality of electrodes are circularly oriented to make circumferential contact with the pulmonary vein ostium.

174. The device of any preceding clause, wherein the device is further configured for visualization, stimulation, recording, and ablation using a plurality of electrodes.

175. The apparatus of any preceding clause, wherein each electrode is configured such that the amount of power delivered to each electrode is independently controlled.

176. The device of any preceding clause, wherein the end probe further comprises a proximal handle, a distal tip, and an intermediate section disposed between the proximal handle and the distal tip.

177. The device of any preceding clause, wherein the proximal handle is a deflection thumb knob that allows for unidirectional deflection, a balloon advancement mechanism, and a luer fitting for balloon inflation and irrigation.

178. The apparatus of any preceding clause, wherein the end probe further comprises

A high torque shaft configured for rotation to facilitate precise positioning of the catheter tip to a desired site; and

deflectable end sections of unidirectional braid.

179. The apparatus of any preceding clause, wherein the end probe further comprises:

A first substrate disposed on the film, the first substrate including a first form of a first radiopaque marking disposed thereon; and

a second substrate disposed on the film, the second substrate including a second radiopaque marking of a second form disposed thereon, the second form being different from the first form.

180. The apparatus of any preceding clause, further comprising an irrigation pump to provide irrigation fluid to and out of the first inflatable membrane.

181. The device of any preceding clause, wherein the validity assessment period is delivery of the tip probe to the pulmonary vein and

at least 91 days after ablating the tissue proximate the pulmonary vein with the tip probe.

182. The device of any preceding clause, wherein the validity assessment period is delivery of the tip probe to the pulmonary vein and

the tissue proximate the pulmonary vein is ablated with the tip probe less than or equal to one year.

183. The apparatus of any preceding clause, wherein the predetermined success rate is 60% for a population size of at least 40 patients.

184. The apparatus of any preceding clause, wherein the population size to achieve the predetermined success rate is at least 300 patients.

185. The apparatus of any preceding clause, wherein the population size to achieve the predetermined success rate is at least 200 patients.

186. The apparatus of any preceding clause, wherein the population size to achieve the predetermined success rate is at least 100 patients.

187. The apparatus of any preceding clause, wherein the population size to achieve the predetermined success rate is at least 50 patients.

188. The apparatus of any preceding clause, wherein the predetermined success rate is at least 60%.

189. The device of any preceding clause, wherein the predetermined success rate is determined by evaluating the patient 7 days after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

190. The device of any preceding clause, wherein the predetermined success rate is determined by evaluating the patient 1 month after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

191. The device of any preceding clause, wherein the predetermined success rate is determined by evaluating the patient 6 months after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

192. The device of any preceding clause, wherein the predetermined success rate is determined by evaluating the patient 12 months after delivering the tip probe to the pulmonary vein and ablating tissue proximate the pulmonary vein with the tip probe.

193. The apparatus of any preceding clause, wherein the predetermined success rate further comprises: confirming entry block in the pulmonary vein after at least one of an adenosine challenge and an isoproterenol challenge.

194. The apparatus of any preceding clause, wherein a patient suffering from at least one of the following events is deemed to have failed pulmonary vein isolation, comprising:

device or procedure related death;

atrial-esophageal fistula, myocardial infarction;

cardiac tamponade/perforation;

thromboembolism;

stroke/cerebrovascular accident (CVA);

transient Ischemic Attack (TIA);

phrenic nerve paralysis, pulmonary vein stenosis;

pericarditis;

pulmonary edema;

macrovascular access complications/bleeding; and

hospitalization (initial or long term).

195. The apparatus of any preceding clause, wherein a patient suffering from at least one of the following events is deemed to have failed pulmonary vein isolation, comprising:

failure of the acute protocol;

After the blanking period (after day 90 post-index protocol), repeated ablation or surgical treatment for AF/AT/atypical (left-sided) AFL;

DC cardioversion, continuous AF/AT/AFL on standard 12-lead ECG for AF/AT/atypical (left-side) AFL, even if the duration of recording is shorter than 30 seconds (after 90 days after exponential procedure);

prescribing new class I and/or class III AAD for AF during the validity assessment period (91 th to 365 th days after the index protocol), or prescribing during the blanking period and the subsequent 90 elapsed days;

during the effectiveness evaluation period, previously failed class I AAD and/or class III AAD (failed at or before screening) are taken at a dose greater than the highest ineffective historical dose for AF; and

amiodarone was prescribed after the protocol.

196. The apparatus of any preceding clause wherein the safety endpoint is defined by a patient suffering from a primary adverse event.

197. The apparatus of any preceding clause, wherein the at least one risk factor of the patient is selected from the group consisting of:

at least three (3) symptomatic episodes of atrial fibrillation lasting ≧ 1 minute for six (6) months prior to the device;

at least one (1) episode of atrial fibrillation recorded as an electrocardiogram for twelve (12) months prior to enrollment, whereby the electrocardiogram recording may include, but is not limited to, an Electrocardiogram (ECG), a holter monitor, or a telemetry strip;

Disabling at least one (1) class I or class III AAD, as evidenced by recurrent symptomatic atrial fibrillation or intolerable side effects against AAD;

age: from 18 to 75 years old;

secondary to electrolyte imbalance;

thyroid disease;

reversible or non-cardiac causes; and

surgical or catheter ablation has previously been performed for atrial fibrillation.

198. The apparatus of any preceding clause, wherein the patient has at least one risk factor selected from the group consisting of:

patients who are known to require ablation outside the PV ostium and CTI region;

atrial fibrillation previously diagnosed as having sustained or long-lasting atrial fibrillation and/or continuing atrial fibrillation 7 days after the device protocol;

any percutaneous coronary intervention was performed within the past 2 months;

prosthetic valve repair or replacement is performed, or a prosthetic valve is present;

any carotid stenting or endarterectomy performed within the past 6 months;

coronary artery bypass grafting, heart surgery or heart valve surgery has been performed within the past 6 months;

left atrial thrombi were recorded within 1 day before the device protocol;

the anterior-posterior diameter of the left atrium is >50 mm;

left ventricular ejection fraction < 40%;

Anticoagulation contraindications;

a history of blood clotting or bleeding abnormalities;

myocardial infarction occurred within the past 2 months;

thromboembolic events (including transient ischemic attacks) were recorded over the past 12 months;

rheumatic heart disease;

uncontrolled heart failure or New York Heart Association (NYHA) class III or IV function;

waiting for a heart transplant or other heart surgery for the next 12 months;

unstable angina pectoris;

acute disease or active systemic infection or sepsis;

diagnosis of atrial myxoma or presence of atrial septal or patches;

there are implanted pacemakers or implantable cardioverter-defibrillators (ICDs);

a major lung disease or any other disease or dysfunction of the lung or respiratory system that produces chronic symptoms;

major congenital abnormalities;

a pregnant woman;

in an investigative study evaluating another device, biological agent, or drug;

known pulmonary vein stenosis;

the presence of an intramural thrombus, tumor or other abnormality that obstructs vascular access or manipulation of the catheter;

the presence of an inferior vena cava filter;

the presence of a disorder that obstructs vascular access;

life expectancy shorter than 12 months or with other disease processes that may limit survival to shorter than 12 months;

Presenting a contraindication to the device; and

patients had been taking amiodarone at any time during the past 3 months prior to enrollment.

199. The device of any preceding clause, wherein if the patient is receiving warfarin/coumarin therapy, the patient must have an international standardized ratio of ≧ 2 for at least 3 weeks prior to the procedure.

200. The device of any preceding clause, wherein if the patient is receiving warfarin/coumarin therapy, it must be confirmed that the patient has an INR of ≧ 2 within 48 hours prior to the procedure.

201. The device of any preceding clause wherein anticoagulation therapy is provided prior to the protocol.

202. The device of any preceding clause wherein the activated clotting time is targeted to 350 to 400 seconds prior to insertion of the catheter and throughout the protocol.

203. The device of any preceding clause, wherein the activated clotting time level is checked every 15 to 30 minutes during the protocol to ensure an activated clotting time target of 350 to 400 seconds.

204. The apparatus of any preceding clause, wherein the multi-electrode circular diagnostic catheter comprises:

an elongated body having a longitudinal axis;

A distal assembly located distal to the elongate body, the distal assembly having a helical form comprising a proximal collar and a distal collar, the proximal and distal collars being angularly oriented relative to the longitudinal axis of the elongate body, and a shape memory support member extending at least through the proximal collar;

at least one irrigated ablation ring electrode mounted on the proximal collar;

a control handle proximal to the elongate body; and

a contraction wire having a proximal end in the control handle and a distal end anchored in the proximal collar, the control handle including a first control member configured to actuate the contraction wire to contract the proximal collar,

wherein the proximal collar has a first flexibility and the distal collar has a second flexibility, and the second flexibility is greater than the first flexibility.

205. Use of an independently controlled multi-electrode radio frequency balloon catheter for treating paroxysmal atrial fibrillation in a predetermined patient population, comprising:

ablating one or more pulmonary vein-targeted tissues using one or more of a plurality of electrodes of an independently controlled multi-electrode radio frequency balloon catheter, the balloon catheter comprising a plurality of electrodes for radio frequency ablation that are independently controllable;

Determining a characteristic of single-freeze Pulmonary Vein Isolation (PVI) success rate based on an ablation parameter of a balloon catheter; and

based on this characteristic and the ablation tissue step, a single cryo-isolation PVI success rate is achieved in all targeted pulmonary vein isolations of the predetermined patient population.

206. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises further ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes based on the characteristic.

207. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises ceasing further ablation of tissue with the multi-electrode radio frequency balloon catheter based on the characteristic.

208. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 91.7% by ablating with a pre-ablation average initial impedance of less than about 95 Ω.

209. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 91.7% by ablating with a highest pre-ablation initial impedance of less than about 100 Ω.

210. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 87% by ablating with a pre-ablation initial anterior wall impedance of less than about 95 Ω.

211. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 85% by ablating with a pre-ablation minimum initial anterior wall impedance of between about 80 Ω to 90 Ω.

212. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 88% by ablating with a pre-ablation highest initial anterior wall impedance of about 110 Ω.

213. The use of clause 205, wherein the step of achieving a single cryo-isolated PVI success rate further comprises achieving a success rate of at least about 87.5% by ablating with a pre-ablation initial anterior wall impedance change impedance range of less than about 20 Ω.

214. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor limiting a maximum initial temperature among the electrodes of the balloon catheter to less than about 31 ℃.

215. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor allowing for a minimum anterior wall impedance approximately between about 80 Ω to 90 Ω.

216. The use of clause 205, wherein the step of achieving a single freeze isolated PVI success rate further comprises achieving a success rate of at least about 90% by ablating with a mean initial impedance of less than about 95 Ω and a highest initial impedance of less than about 110 Ω.

217. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a mean onset temperature, and wherein the mean onset temperature is approximately less than about 28 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

218. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed onset temperature, and wherein the distributed onset temperature is approximately greater than about 31 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

219. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed onset temperature, and wherein the distributed onset temperature is approximately greater than about 30 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

220. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a distributed onset temperature, and wherein the distributed onset temperature is approximately greater than about 29 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

221. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature slope, and wherein the pre-ablation minimum temperature slope is approximately greater than about 0.75 ℃/s, and the single freeze isolated PVI success rate is approximately at least about 90%.

222. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature, and wherein the pre-ablation minimum temperature is approximately greater than about 6 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

223. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation maximum initial temperature, and wherein the pre-ablation maximum initial temperature is approximately less than about 31 ℃, and the single freeze isolated PVI success rate is approximately at least about 90%.

224. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation initial temperature variation, and wherein the pre-ablation initial temperature variation is approximately less than about 3 ℃, and the single freeze isolated PVI success rate is approximately at least about 95%.

225. The use of clause 205, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation initial impedance variation, and wherein the pre-ablation initial impedance variation comprises an optimal range of approximately less than about 20 Ω, and the single freeze isolation PVI success rate is approximately at least about 88.5%.

226. The use of clause 205, wherein the characteristic is a predictor of single freeze isolated PVI success rate prior to ablation, the predictor being a pre-ablation minimum impedance dip, and wherein the pre-ablation minimum impedance dip is approximately greater than about 12 Ω, and the single freeze isolated PVI success rate is approximately at least about 90%.

227. The use of clause 205, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being pre-ablation impedance dip variation, and wherein the pre-ablation impedance dip variation is approximately greater than about 20 Ω and the single freeze isolation PVI success rate is approximately at least about 85%.

228. The use of clause 205, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a percentage of pre-ablation minimum impedance drop, and wherein the percentage of pre-ablation minimum impedance drop is approximately greater than or equal to about 12%, and the single freeze isolation PVI success rate is approximately at least about 90%.

229. The use of clause 205, wherein the characteristic is a predictor of single freeze isolation PVI success rate prior to ablation, the predictor being a pre-ablation impedance drop percentage change, and wherein the pre-ablation impedance drop percentage change is less than about 20 Ω, and the single freeze isolation PVI success rate is approximately at least about 85%.

230. The use of clause 205, wherein the single freeze isolation PVI success rate is approximately about 92% when the number of electrodes having an initial impedance deviation from the average is zero.

231. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, the predictor being the difference in impedance between the anterior wall and the posterior wall.

232. The use of clause 231, wherein the difference is approximately less than about 20 Ω for the predetermined patient population and the single-freeze PVI success rate is approximately at least about 85%.

233. The use of clause 231, wherein the difference is approximately less than about 20 Ω and the single-freeze PVI success rate is approximately at least about 85% for a predetermined patient population of at least 25 patients.

234. The use of clause 231, wherein the difference is approximately between 20 Ω to 30 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 78%.

235. The use according to clause 231, wherein the difference is approximately between 20 Ω to 30 Ω for a predetermined patient population of at least 75 patients, and the single freeze PVI success rate is approximately at least about 78%.

236. The use of clause 231, wherein the difference is approximately between 30 Ω -40 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 75%.

237. The use of clause 231, wherein the difference is approximately between 30 Ω -40 Ω and the single-freeze PVI success rate is approximately at least about 75% for a predetermined patient population of at least 60 patients.

238. The use of clause 231, wherein the difference is approximately between 40 Ω to 50 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 67%.

239. The use of clause 231, wherein the difference is approximately between 40 Ω to 50 Ω for a predetermined patient population of at least 34 patients, and the single-freeze PVI success rate is approximately at least about 67%.

240. The use of clause 231, wherein the difference is approximately between 50 Ω to 60 Ω for the predetermined patient population, and the single freeze PVI success rate is approximately at least about 35%.

241. The use of clause 231, wherein the difference is approximately between 50 Ω -60 Ω and the single-freeze PVI success rate is approximately at least about 35% for a predetermined patient population of at least 11 patients.

242. The use of clause 231, wherein the difference is approximately greater than about 60 Ω and the single-freeze PVI success rate is approximately at least about 33% for the predetermined patient population.

243. The use of clause 231, wherein the difference is approximately greater than about 60 Ω and the single-freeze PVI success rate is approximately at least about 33% for a predetermined patient population of at least 9 patients.

244. The use of clause 231, wherein the balloon catheter is a full circumferential full electrode combustion ablation catheter.

245. The use of clause 231, wherein the step of ablating the tissue lasts for 60 seconds.

246. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation average initial impedance is the predictor.

247. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation initial impedance change is the predictor.

248. The use according to clause 205, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the minimum impedance after ablation falls to the assessment factor.

249. The use according to clause 205, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation impedance drop varies as the assessment factor.

250. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein post-ablation average temperature slope is the evaluation factor.

251. The use of clause 205, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the minimum temperature slope after ablation is a predictor.

252. The use according to clause 205, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein post-ablation average temperature rise is the assessment factor.

253. The use of clause 205, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein post-ablation coldest temperature rises to the assessment factor.

254. The use of clause 205, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the percentage of minimum impedance drop after ablation is the assessment factor.

255. The use according to clause 205, wherein the characteristic is an assessment factor of single cryo-isolation PVI success rate after ablation, and wherein the percentage of impedance drop after ablation varies as the assessment factor.

256. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation minimum impedance falls to the predictor.

257. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation initial temperature change is the predictor.

258. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation maximum initial impedance is the predictor.

259. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the pre-ablation average initial anterior wall impedance is the predictor.

260. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation minimum anterior wall impedance is the predictor.

261. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation maximum anterior wall impedance is the predictor.

262. The use of clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein pre-ablation anterior wall impedance variation is the predictor.

263. The use according to clause 205, wherein the impedance value is an impedance value among the electrodes of the front wall.

264. The use according to clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～4.367-0.420ΔT₀-0.0486ΔZ₀

Wherein Δ T₀Is the initial impedance change and Δ Z₀Is the initial temperature change.

265. The use according to clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～26.78-0.576T_0max-0.0632Z_0max

wherein T is_0maxIs the maximum initial temperature and Z_0maxThe highest initial impedance.

266. The use according to clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～27.70-0.540T_0max-0.0959Z_0max

wherein T is_0maxIs the maximum initial temperature and Z_0maxThe highest initial impedance.

267. The use according to clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～9.31-0.408ΔT₀-0.0544Z_0max

wherein Δ T₀Is an initial temperature change and Z_0maxThe highest initial impedance.

268. The use according to clause 205, the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～22.61-0.622T_0max-0.0626ΔZ₀

wherein T is_0maxIs the maximum initial temperature and Δ Z₀Is the initial impedance change.

269. The use according to clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～11.53-0.439ΔT₀-0.0856Z_0mean

Wherein Δ T₀Is an initial temperature change and Z_0meanIs the average initial impedance.

270. The use according to clause 205, wherein the characteristic is a predictor of single cryo-isolation PVI success rate prior to ablation, and wherein the predictor is determined by:

Y～26.52+0.013ΔT₀-0.594T_0max-0.0122ΔZ₀-0.0535Z_0max

wherein Δ T₀For initial temperature change, T_0maxAt the maximum initial temperature,. DELTA.Z₀Is an initial impedance change, and Z_0maxThe highest initial impedance.

271. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.562+0.2856ΔT_min-0.0629ΔZ_drop

wherein Δ T_minIs the lowest temperature rise and Δ Z_dropIs the impedance drop change.

272. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～-0.507+0.206ΔT_min+0.083Z_dropmin

wherein Δ T_minIs the lowest temperature rise and Z_dropminThe minimum impedance drop.

273. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.248+0.2486ΔT_min-0.0594ΔZ_drop+0.0419Z_dropmin

wherein Δ T_minIs the lowest temperature rise and Z _dropminThe minimum impedance drop.

274. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.174+0.2515ΔT_min-0.0564ΔZ_drop％

wherein Δ T_minIs the lowest temperature rise and Δ Z_dropIs the percent change in impedance drop.

275. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～-0.644+0.170ΔT_min+0.107Z_drop％_min

wherein Δ T_minIs the lowest temperature rise and Z_drop％_minIs the lowest percent impedance drop.

276. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～0.339+0.187ΔT_min+0.0737Z_drop％_min-0.0368ΔZ_drop％

wherein Δ T_minAt the lowest temperature rise, Z_drop％_minIs the minimum percent impedance drop, and Δ Z_drop% is the percent change in impedance drop.

277. The use according to any preceding clause, wherein the characteristic is an assessment factor for single cryo-isolation PVI success rate after ablation, and wherein the assessment factor is determined by:

Y～1.043+0.777T′_min+0.171ΔT_min+0.0479Z_drop-min-0.0589ΔZ_drop

wherein T'_minIs the lowest temperature slope, Δ T_minAt the lowest temperature rise, Z _drop-minIs the lowest impedance drop, and Δ Z_dropIs the impedance drop change.

278. The use of clause 205, further comprising the step of displaying the independently controllable electrodes and the graphical representation of the ablation parameter.

279. The use of clause 278, wherein one ablation parameter comprises an impedance measured proximate each electrode.

280. The use of clause 279, wherein the measured impedance comprises an impedance measured prior to ablation.

281. The use of clause 279, wherein the measured impedance comprises an impedance measured after ablation.

282. The use of clause 279, wherein the measured impedance comprises an impedance measured before ablation and an impedance measured after ablation.

283. The use of clause 278, wherein one ablation parameter comprises a temperature measured proximate each electrode.

284. The use of clause 278, wherein the one ablation parameter comprises a maximum temperature measured proximate each electrode during ablation.

285. The use of clause 278, wherein one ablation parameter comprises a temperature rise measured from the start of ablation to the end of ablation.

286. Use of an independently controlled multi-electrode radio frequency balloon catheter for treating paroxysmal atrial fibrillation in a plurality of patients, comprising the steps of:

Delivering a multi-electrode diagnostic catheter and a radio frequency balloon catheter having a plurality of independently controllable electrodes for radio frequency ablation to one or more targeted pulmonary veins;

ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter;

diagnosing one or more targeted pulmonary veins using a multi-electrode diagnostic catheter; and

at least one of a predetermined clinical effectiveness and an acute effectiveness of the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter is achieved in the isolation of the one or more targeted pulmonary veins during and approximately 3 months after the ablating step.

287. The use of clause 286, wherein acute efficacy is defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge.

288. The use of clause 287, further comprising: determining the acute effectiveness determined at about 3 months after the ablating step; and

based on the acute effectiveness determined at about 3 months, an estimated acute effectiveness is generated at about 12 months after the ablation step.

289. The use of clause 288, wherein the estimated acute effectiveness at about 12 months is substantially similar to the acute effectiveness determined at about 3 months.

290. The use of clause 287, wherein the acute effectiveness is further defined by a success rate of greater than 90% for the plurality of patients.

291. The use of clause 287, wherein the acute effectiveness is further defined by a success rate of greater than 95% for the plurality of patients.

292. The use of clause 287, wherein the confidence of acute and clinical effectiveness of all targeted veins type 1 error rates are controlled at a level of about 5%, the method or use further comprising:

if both the acute and clinical effectiveness indicators are controlled at a level of about 5%, then it is determined whether ablation is clinically successful for a plurality of patients.

293. The use of clause 287, wherein the acute effectiveness is at least 80% for a plurality of at least 80 patients.

294. The use of clause 287, wherein the acute effectiveness is at least 80% for a plurality of at least 130 patients.

295. The use of clause 287, wherein the acute effectiveness is at least 80% for a plurality of at least 180 patients.

296. The use of clause 287, wherein the acute effectiveness is at least 80% for a plurality of at least 230 patients.

297. The use of clause 287, wherein the acute effectiveness is further defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge with the use of a focal ablation catheter.

298. The use of clause 287, wherein the acute effectiveness is further defined by confirming whether there is an entry block in all targeted pulmonary veins after an adenosine and/or isoproterenol challenge without the use of a focal ablation catheter.

299. The use of clause 286, wherein the ablation is administered to a plurality of patients diagnosed with symptomatic paroxysmal atrial fibrillation.

300. The use of clause 286, wherein the diagnosing step further comprises:

electrophysiological mapping of the heart.

301. The use of clause 286, wherein the multi-electrode diagnostic catheter further comprises a high torque shaft having a halo-shaped tip section comprising a plurality of pairs of electrodes visible under fluoroscopy.

302. The use of clause 286, wherein the plurality of patients is at least 80.

303. The use of clause 286, wherein the plurality of patients is at least 130.

304. The use of clause 286, wherein the plurality of patients is at least 180.

305. The use of clause 286, wherein the plurality of patients is at least 230.

306. The use of clause 286, wherein the predetermined acute effectiveness is defined by the absence of an ulcer in the plurality of patients after ablation.

307. The use of clause 286, wherein the predetermined acute effectiveness is defined by a complication rate of about 13% or less of esophageal erythema experienced by a plurality of patients after ablation.

308. The use of clause 286, wherein the predetermined acute effectiveness is defined by a complication rate of about 25% or less of a plurality of patients experiencing a new asymptomatic thromboembolic lesion after ablation.

309. The use of clause 286, wherein the predetermined acute effectiveness is defined by a complication rate of about 20% or less of a plurality of patients experiencing a new asymptomatic thromboembolic lesion after ablation.

310. The use of clause 286, wherein the predetermined acute effectiveness is defined by a complication rate of about 5% to 9% or less of the plurality of patients experiencing the primary adverse event about 7 days or more after ablation.

311. The use of clause 286, wherein the inclusion criteria for the plurality of patients comprises:

diagnosed as having symptomatic paroxysmal atrial fibrillation; and

the patient is able to comply with the ongoing on-schedule anticoagulation requirements.

312. The use of clause 286, wherein the predetermined acute effectiveness is defined by a total protocol time.

313. The use of clause 286, wherein the predetermined acute effectiveness is defined by a total ablation time.

314. The use of clause 286, wherein the predetermined acute effectiveness is defined by a total radio frequency application time.

315. The use of clause 286, wherein the predetermined acute effectiveness is defined by a total dwell time of the multi-electrode radio frequency balloon catheter.

316. The use of clause 286, wherein the predetermined acute effectiveness is defined by isolating the total time of all targeted pulmonary veins.

317. The use of clause 286, wherein the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radio frequency balloon catheter at each location of all targeted pulmonary veins.

318. The use of clause 286, wherein the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radio frequency balloon catheter to each patient.

319. The use of clause 286, wherein the predetermined acute effectiveness is defined by the number of applications and the total time of application of the multi-electrode radio frequency balloon catheter to each targeted vein.

320. The use of any preceding clause, wherein the multi-electrode radiofrequency balloon catheter comprises:

a compliant balloon incorporating a plurality of electrodes configured to deliver radio frequency energy to tissue of a pulmonary vein and sense a temperature at each electrode.

321. The use of clause 320, wherein clinical effectiveness is defined by the incidence of early onset of one or more adverse events within a predetermined time of the method or use being performed.

322. The use of clause 321, wherein the predetermined time is at least 7 days.

323. The use of clause 321, wherein the one or more adverse events comprise: death, atrial-esophageal fistula, myocardial infarction, cardiac packing/perforation, thromboembolism, stroke, TIA (transient ischemic attack), phrenic nerve paralysis, pulmonary vein stenosis, and large vessel access bleeding.

324. The use of clause 321, wherein the one or more adverse events comprise: the incidence of individual adverse events from the primary composite event; the incidence of serious adverse device effects; incidence of severe adverse events within 7 days, at least 7 days to 30 days, and at least 30 days post ablation; the incidence of non-serious adverse events; the incidence of asymptomatic and symptomatic cerebral embolism as determined by MRI assessment before and after ablation; and the frequency, anatomical location and size (diameter and volume) of cerebral emboli assessed by MRI at baseline, post-ablation and during follow-up.

325. The use of clause 321, wherein about 5% to 9% of the plurality of patients develop one or more adverse events comprising:

NIHSS (national institute of health stroke scale) scores at baseline, post-ablation, and during follow-up;

a summary of MoCA (montreal cognitive assessment) scores and mRS (modified Rankin scale) scores at baseline, 1 month, and during further follow-up; the hospitalization rate for cardiovascular events; percentage (%) of pulmonary vein isolation supplemental ablation by focal catheter among the one or more targeted veins;

percent (%) of subjects with non-PV triggering using focal catheter ablation;

(ii) percentage (%) of subjects with no recorded symptomatic Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left side) Atrial Flutter (AFL) episodes (> 30 seconds of episodes from day 91 to day 180 on arrhythmia monitoring device);

percent (%) of subjects with no recorded Atrial Fibrillation (AF), Atrial Tachycardia (AT), or atypical (left-sided) Atrial Flutter (AFL);

one or more episodes lasting 30 seconds or more on the arrhythmia monitoring device from day 91 to day 180 after ablation; and

One or more protocol parameters including total protocol and ablation time, balloon dwell time, radio frequency application times, fluoroscopy time and dose.

326. The use of clause 320, wherein the acute safety rate comprises a complication rate of 10% or less and is defined by the incidence of asymptomatic cerebral embolic lesions upon discharge electromagnetic resonance imaging (MRI).

327. The use according to clause 320, wherein the acute effective rate is 100% and is defined by electrically isolating all targeted pulmonary veins without the use of a focal ablation catheter.

328. The use according to clause 320, wherein acute effective rate is defined by determining no recorded atrial fibrillation, atrial tachycardia or atypical atrial flutter onset based on electrocardiographic data over an entire validity assessment period (1 year).

329. The use according to clause 320, wherein acute effective rate is defined by pulmonary vein isolation supplemental ablation of a focal catheter among all targeted pulmonary veins.

330. The use according to clause 320, wherein the predetermined clinical effectiveness rate is defined by a complication rate of 10% or less associated with the incidence of symptomatic and asymptomatic cerebral embolism after ablation as compared to before ablation.

331. The use of clause 320, wherein the multi-electrode diagnostic catheter is configured for electrophysiological recording and stimulation of an atrial region of a heart and is used in conjunction with the multi-electrode radio frequency balloon catheter.

332. Use of an independently controlled multi-electrode radio frequency balloon catheter for treating paroxysmal atrial fibrillation in a plurality of patients, comprising:

delivering a multi-electrode diagnostic catheter and a radio frequency balloon catheter having a plurality of independently controllable electrodes for radio frequency ablation to one or more targeted pulmonary veins; and

ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter;

diagnosing all targeted pulmonary veins using a multi-electrode diagnostic catheter; and

during and approximately 6 months after the method or use, a predetermined adverse event rate based on the use of the multi-electrode radio frequency balloon catheter and the multi-electrode diagnostic catheter in isolation of all targeted pulmonary veins is achieved.

333. Use of an independently controlled multi-electrode radio frequency balloon catheter for treating paroxysmal atrial fibrillation in a plurality of patients, comprising the steps of:

assessing the number and size of all targeted pulmonary veins and anatomical structures of the left atrium;

Puncturing the transseptal space;

selectively positioning a multi-electrode esophageal temperature monitoring device in the vasculature relative to all targeted pulmonary veins;

selectively positioning a radio frequency balloon catheter in the vasculature relative to all targeted pulmonary veins, the multi-electrode radio frequency balloon catheter having a plurality of independently controllable electrodes for radio frequency ablation;

selectively positioning a multi-electrode diagnostic catheter in the vasculature relative to all targeted pulmonary veins;

ablating all tissue targeted to the pulmonary veins with one or more of the plurality of electrodes of the independently controlled multi-electrode radio frequency balloon catheter;

confirming isolation of all targeted pulmonary veins using a multi-electrode diagnostic catheter;

confirming the presence of entry blockages in all targeted pulmonary veins;

based on confirming the presence of the entry block, a predetermined clinical effectiveness and/or acute effectiveness of the method or use is achieved that is associated with isolating all targeted pulmonary veins according to the method or use.

334. The use of any preceding clause, further comprising: all targeted pulmonary veins are mapped using a diagnostic catheter.

335. The use of any preceding clause, wherein the exclusion criteria for the plurality of patients comprises at least one of:

Atrial fibrillation secondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac causes;

previous surgical or catheter ablation for atrial fibrillation;

ablation is expected to be received outside all targeted pulmonary vein ostia and CTI regions;

previously diagnosed as having sustained, long-term atrial fibrillation and/or >7 days of continuous atrial fibrillation, or >48 hours of pre-cardioversion symptoms;

any Percutaneous Coronary Intervention (PCI) performed within the last 2 months;

valve repair or replacement and the presence of a prosthetic valve;

any carotid stenting or endarterectomy performed;

coronary artery bypass graft, heart surgery, heart valve surgery, or percutaneous surgery has been performed within the past 6 months;

left atrial thrombus recorded on baseline imaging;

the anterior-posterior diameter of the left atrium is greater than 50 mm;

the diameter of any pulmonary vein is greater than or equal to 26 mm;

left ventricular ejection fraction less than 40%;

anticoagulation contraindications;

a history of clotting or bleeding abnormalities;

myocardial infarction occurred within the past 2 months;

thromboembolic events were recorded over the past 12 months;

rheumatic heart disease;

Wait for a heart transplant or other heart surgery for the next 12 months;

unstable angina pectoris;

acute disease or active systemic infection or sepsis;

diagnosis as atrial myxoma or atrial septum or patch;

presence of implanted pacemakers, implantable cardioverter defibrillators, tissue-embedded or ferrous metal debris;

major lung disease or any other disease or dysfunction of the lung or respiratory system that produces chronic symptoms;

major congenital abnormalities;

gestation or lactation;

enrollment in an investigative study evaluating another device, biological agent or drug;

pulmonary vein stenosis;

the presence of an intramural thrombus, tumor or other abnormality that obstructs vascular access or manipulation of the catheter;

presence of an IVC filter;

presence of a disorder obstructing the vascular access;

life expectancy shorter than 12 months or with other disease processes that may limit survival to shorter than 12 months;

contraindications for the use of MRI contrast agents;

the presence of ferrous metal debris in the patient; or

Unresolved preexisting neurological deficits.

336. The use of any preceding clause, wherein the multi-electrode radiofrequency balloon catheter comprises:

A compliant balloon having a plurality of electrodes configured to deliver radio frequency energy to all tissue targeting the pulmonary vein and sense temperature at each electrode.

337. The use of clause 336, wherein the plurality of electrodes are circularly oriented to make circumferential contact with the pulmonary vein ostium.

338. The use of clause 336, further comprising using a plurality of electrodes for visualization, stimulation, recording, and ablation.

339. The use of clause 336, wherein each electrode is configured such that the amount of power delivered to each electrode is independently controlled.

340. The use of clause 336, wherein the multi-electrode radio frequency balloon catheter further comprises a proximal handle, a distal tip, and an intermediate section disposed between the proximal handle and the distal tip.

341. The use of clause 340, wherein the proximal handle is a deflecting thumb knob that allows for unidirectional deflection, a balloon advancement mechanism, and a luer fitting for balloon inflation and irrigation. 342. The use of clause 336, wherein the multi-electrode radiofrequency balloon catheter further comprises

A high torque shaft configured for rotation to facilitate precise positioning of the catheter tip to a desired site; and

Deflectable end sections of unidirectional braid.

343. The use of any preceding clause, further comprising:

and (3) controlling the perfusion of the multi-electrode radio-frequency balloon catheter by using a perfusion pump.

344. The use of any preceding clause, further comprising:

uninterrupted anticoagulant therapy is administered at least 1 month prior to the protocol.

345. The use according to any preceding clause, wherein if the patient is receiving warfarin/coumarin therapy, the patient must have an International Normalized Ratio (INR) of ≧ 2 for at least 3 weeks prior to the procedure.

346. The use according to any preceding clause, wherein if the patient is receiving warfarin/coumarin therapy, it must be confirmed that the patient has an International Normalized Ratio (INR) of ≧ 2 within 48 hours prior to the procedure.

347. The use of any preceding clause, further comprising: anticoagulation therapy was continued prior to the protocol.

348. The use of any preceding clause, further comprising:

administering a transseptal puncture;

confirm an activated clotting time target of ≧ 350 seconds prior to insertion of the multi-electrode radiofrequency balloon catheter into the left atrium, and maintain the target throughout the procedure;

introducing a multi-electrode radio frequency balloon catheter;

Introducing a multi-electrode circular diagnostic catheter;

ablating pulmonary veins with a multi-electrode radio frequency balloon catheter;

determining pulmonary vein isolation in real time by using a multi-electrode circular diagnostic catheter; and

it is confirmed whether the access in the pulmonary vein is blocked.

349. The use of any preceding clause, wherein the multi-electrode circular diagnostic catheter comprises:

an elongated body having a longitudinal axis;

a distal assembly located distal to the elongate body, the distal assembly having a helical form comprising a proximal collar and a distal collar, the proximal and distal collars being angularly oriented relative to the longitudinal axis of the elongate body, and a shape memory support member extending at least through the proximal collar;

at least one irrigated ablation ring electrode mounted on the proximal collar;

a control handle proximal to the elongate body; and

a contraction wire having a proximal end in the control handle and a distal end anchored in the proximal collar, the control handle including a first control member configured to actuate the contraction wire to contract the proximal collar,

Wherein the proximal collar has a first flexibility and the distal collar has a second flexibility, and the second flexibility is greater than the first flexibility.

350. Use of an independently controlled multi-electrode radio frequency balloon catheter to treat paroxysmal atrial fibrillation in a plurality of patients by applying energy to subject cardiac tissue proximate the esophagus, phrenic nerve, or lung, comprising the steps of:

based on using a radio frequency balloon catheter and a multi-electrode diagnostic catheter in isolation of one or more targeted pulmonary veins to achieve at least one of a predetermined clinical effectiveness and acute effectiveness of a procedure by:

positioning an expandable member proximate the left atrium, the expandable member of a multi-electrode radio frequency balloon catheter having a longitudinal axis and comprising a plurality of electrodes disposed about the longitudinal axis, each electrode being independently energizable, the plurality of electrodes comprising a first electrode having a first radiopaque marking and a second electrode having a second radiopaque marking different from the first radiopaque marking;

viewing an image of the expandable member and the first and second radiopaque markings in the left atrium;

determining an orientation of the first and second radiopaque markings relative to a portion of a left atrium of the subject that is closest to an esophagus, phrenic nerve, or lung;

Moving one of the first and second radiopaque markers to a portion of the left atrium closest to the esophagus, phrenic nerve, or lung;

energizing one or more electrodes indexed proximate to one of the radiopaque markers proximate to the portion proximate to the esophagus, phrenic nerve, or lung at a lower energization setting than the other electrodes to create a transmural lesion in the left atrium with little or no effect on adjacent anatomical structures; and

electrophysiological recording and stimulation of the atrial region of tissue proximate the esophagus, phrenic nerve, or lung was performed using a multi-electrode diagnostic catheter.

351. An ablation system for electrical signal isolation in a portion of organ tissue, the system comprising:

a power generator;

a catheter shaft extending along a longitudinal axis;

a plurality of electrodes disposed about the longitudinal axis to define at least a circumferential surface about the longitudinal axis, each electrode independently connected to a power generator to provide electrical energy to each independent electrode; and

a processor for controlling power delivery by the power generator to each of the independently controlled electrodes, the processor configured to:

(a) Receiving measurement signals indicative of tissue temperature and tissue impedance proximate each electrode in contact with the organ tissue, an

(b) An indication of a probability of success of isolating electrical signal propagation in a region of organ tissue in contact with the plurality of electrodes is provided, the probability of success being determined from the tissue temperature value and the tissue impedance value.

352. The system of clause 351, wherein

The temperature value is selected from one or more of the following: (a) a maximum initial temperature; (b) a change in initial temperature; (c) the lowest temperature rise; (d) a minimum temperature slope; (e) an average temperature slope; (f) average temperature rise; and is

The impedance value is selected from one or more of the following:

(a) a change in initial impedance; (b) the highest initial impedance; (c) averaging the initial impedance; (d) initial impedance deviations from the mean for all electrodes; (d) a change in impedance drop; (e) the lowest impedance drop; (f) percent of lowest impedance drop; (g) change in percent resistance drop.

353. The system of clause 352, wherein the success indicator is about 90% when the initial impedance is less than about 20 ohms.

354. The system of clause 352, wherein the success indication is greater than 90% when the highest initial impedance is less than about 110 Ω.

355. The system of clause 352, wherein the success indicator is greater than 90% when the average initial impedance is less than about 95 Ω.

356. The system of clause 352, wherein the success indication is greater than 90% when the maximum initial temperature is less than about 31 degrees celsius.

357. The system of clause 352, wherein the success indication is greater than 90% when the initial temperature change is less than about 3 ℃.

358. The system of clause 352, wherein the success indication is greater than 90% when the number of electrodes having an initial impedance deviation from the average is zero.

359. The system of clause 352, wherein the success indicator is greater than 85% and the impedance drop varies by less than about 20 Ω.

360. The system of clause 352, wherein the success indicator is greater than 90% when the minimum temperature rise is equal to or greater than about 6 ℃.

361. The system of clause 352, wherein the success indicator is greater than 90% when the minimum impedance drop is equal to or greater than about 12 Ω.

362. The system of clause 352, wherein the success indicator is greater than 90% when the minimum impedance reduction percentage is equal to or greater than about 12%.

363. The system of clause 352, wherein the success indicator is greater than 90% when the minimum temperature slope is equal to or greater than about 0.75 ℃/s.

364. The system of clause 352, wherein a success indicator is greater than 90% when the average temperature rise is equal to or greater than about 14 ℃.

365. The system of clause 351, wherein the temperature value is selected from one or more of the following: (a) initial temperature change Δ T₀(ii) a (b) Maximum initial temperature T_0max(ii) a (c) Minimum temperature rise delta T_min(ii) a And is

Wherein the impedance value is selected from one or more of: (a) initial impedance change Δ Z₀(ii) a (b) Highest initial impedance Z_0max(ii) a (c) Mean initial impedance Z_0mean(ii) a (d) Change in impedance drop Δ Z_drop(ii) a (e) Lowest impedance drop Z_dropmin(ii) a (f) Percent change in impedance drop Δ Z_dropPercent; (g) percent decrease in minimum impedance Z_drop％_min。

366. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 4.167-0.220 Δ T₀-0.0286ΔZ₀。

367. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 9.11-0.208 Δ T₀-0.0524Z_0max。

368. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 11.53 to 0.219 Δ T₀-0.0856Z_0mean。

369. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 2.61-0.62T_0max-0.066ΔZ₀。

370. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 2.61-0.62T_0max-0.066ΔZ₀。

371. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 6.78-0.576T_0max-0.0612Z_0max。

372. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 7.70-0.520T_0max-0.0959Z_0mean。

373. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 6.52+0.013 Δ T₀-0.594T_0max-0.012ΔZ₀-0.0315Z_0max。

374. The system of clause 365, wherein the probability of success is approximately equal to

Wherein Y is about 1.562+0.856 Δ T_min-0.069ΔZ_drop。

375. The method of clause 365Wherein the probability of success is approximately equal to

And Y is about-0.307 +0.206 Δ T_min+0.083Z_dropmin。

376. The system of clause 365, wherein the probability of success is approximately equal to

And Y is about 1.28+0.286 Δ T_min-0.0594ΔZ_drop+0.0219Z_dropmin。

377. The system of clause 365, wherein the probability of success is approximately equal to

And Y is about 1.174+0.315 Δ T_min-0.0564ΔZ_drop％。

378. The system of clause 365, wherein the probability of success is approximately equal to

And Y is about-0.624 +0.170 Δ T_min+0.107Z_drop％min。

379. The system of clause 365, wherein the probability of success is approximately equal to

And Y is about 0.119+0.1867 Δ T_min+0.0717Z_drop％min-0.0168ΔZ_drop％。

380. The system of clause 351, wherein the probability of success is selected from one or more of clauses 352-379.

The methods or uses, systems and devices of the present disclosure demonstrate a high rate of significant clinical effectiveness and safety in patients with PAF. The particular configuration, choice of materials, and size and shape of the various elements can be varied according to design specifications or constraints as desired for a system or method or use constructed in accordance with the principles of the disclosed technology. Such variations are intended to be included within the scope of the disclosed technology. The presently disclosed embodiments are therefore considered in all respects to be illustrative and not restrictive. It will thus be apparent from the foregoing that while particular forms of the disclosure have been illustrated and described, various modifications may be made without departing from the spirit and scope of the invention, and all changes that come within the meaning and range of equivalents thereof are intended to be embraced therein.

Claims (29)

1. An ablation system for electrical signal isolation in a portion of organ tissue, the system comprising:

a power generator;

a catheter shaft extending along a longitudinal axis;

a plurality of electrodes disposed about the longitudinal axis to define at least a circumferential surface about the longitudinal axis, each electrode independently connected to the power generator to provide electrical energy to each independent electrode; and

a processor for controlling power delivery by the power generator to each of the independently controlled electrodes, the processor configured to:

(c) receiving measurement signals representative of tissue temperature and tissue impedance proximate each electrode in contact with organ tissue; and

(d) providing an indication of a probability of success of electrical signal propagation in a region of the organ tissue isolated from contact with the plurality of electrodes, the probability of success being determined from a tissue temperature value and a tissue impedance value.

2. The system of claim 1, wherein the temperature value is selected from one or more of the following:

(a) initial temperature change Δ T₀(ii) a (b) Maximum initial temperature T_0max(ii) a Or (c) minimum temperature rise DeltaT_min(ii) a And is

Wherein the impedance value is selected from one or more of the following: (a) initial impedance change Δ Z ₀；

(b) Highest initialStarting impedance Z_0max(ii) a (c) Mean initial impedance Z_0mean(ii) a (d) Change in impedance drop Δ Z_drop；

(e) Lowest impedance drop Z_dropmin(ii) a (f) Percent change in impedance drop Δ Z_dropPercent; or (g) percent decrease in minimum impedance Z_drop％_min。

3. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 4.167-0.220 Δ T₀-0.0286ΔZ₀。

4. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 9.11-0.208 Δ T₀-0.0524Z_0max。

5. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 11.53 to 0.219 Δ T₀-0.0856Z_0mean。

6. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 2.61-0.62T_0max-0.066ΔZ₀。

7. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 2.61-0.62T_0max-0.066ΔZ₀。

8. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 6.78-0.576T_0max-0.0612Z_0max。

9. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 7.70-0.520T_0max-0.0959Z_0mean。

10. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 6.52+0.013 Δ T₀-0.594T_0max-0.012ΔZ₀-0.0315Z_0max。

11. The system of claim 2, wherein the probability of success is approximately equal to

Wherein Y is about 1.562+0.856 Δ T_min-0.069ΔZ_drop。

12. The system of claim 2, wherein the probability of success is approximately equal to

And Y is about-0.307 +0.206 Δ T_min+0.083Z_dropmin。

13. The system of claim 2, wherein the probability of success is approximately equal to

And Y is about 1.28+0.286 Δ T_min-0.0594ΔZ_drop+0.0219Z_dropmin。

14. The system of claim 2, wherein the probability of success is approximately equal to

And Y is about 1.174+0.315 Δ T_min-0.0564ΔZ_drop％。

15. The system of claim 2, wherein the probability of success is approximately equal to

And Y is about-0.624 +0.170 Δ T_min+0.107Z_drop％_min。

16. The system of claim 2, wherein the probability of success is approximately equal to

And Y is about 0.119+0.1867 Δ T_min+0.0717Z_drop％_min-0.0168ΔZ_drop％。

17. The system of claim 1, wherein the temperature signal comprises a signal obtained from a temperature sensor disposed proximate each of the plurality of electrodes.

18. The system of claim 1, wherein the impedance signal comprises a signal representative of tissue impedance measured proximate each of the plurality of electrodes.

19. A method of treating paroxysmal atrial fibrillation in a predetermined patient population, the method comprising:

ablating one or more tissues targeted to the pulmonary veins with one or more of the plurality of electrodes of the radio frequency balloon catheter;

Determining a characteristic of single-freeze Pulmonary Vein Isolation (PVI) success rate based on an ablation parameter of the balloon catheter; and

achieving a single cryo-isolation PVI success rate in said isolating of all targeted pulmonary veins of said predetermined patient population based on said characteristics and ablating tissue steps.

20. The method of claim 19, wherein the step of achieving the single freeze-isolated PVI success rate further comprises achieving a success rate of at least about 91.7% by ablating with a pre-ablation average initial impedance of less than about 95 Ω.

21. The method of claim 19, wherein the step of achieving the single freeze-isolated PVI success rate further comprises achieving a success rate of at least about 88% by ablating with a pre-ablation highest initial anterior wall impedance of about 110 Ω.

22. The method of claim 19, wherein the step of achieving the single freeze-isolated PVI success rate further comprises achieving a success rate of at least about 87.5% by ablating with a pre-ablation initial anterior wall impedance change impedance range of less than about 20 Ω.

23. The method of claim 19, wherein the characteristic is a predictor of the single cryo-isolation PVI success rate prior to ablation, the predictor limiting a maximum initial temperature among the electrodes of the balloon catheter to less than about 31 ℃.

24. The method of claim 19, wherein the step of achieving the single freeze-isolated PVI success rate further comprises achieving a success rate of at least about 90% by ablating with an average initial impedance of less than about 95 Ω and a highest initial impedance of less than about 110 Ω.

25. The method of claim 19, wherein the characteristic is a predictor of the single freeze isolated PVI success rate prior to ablation, the predictor being a mean initial temperature, and wherein the mean initial temperature is approximately less than about 28 ℃ and the single freeze isolated PVI success rate is approximately at least about 90%.

26. The method of claim 19, wherein the characteristic is a predictor of the single freeze-isolated PVI success rate prior to ablation, the predictor being a pre-ablation minimum temperature slope, and wherein the pre-ablation minimum temperature slope is approximately greater than about 0.75 ℃/s and the single freeze-isolated PVI success rate is approximately at least about 90%.

27. The method of claim 19, wherein the characteristic is a predictor of the single freeze-isolation PVI success rate prior to ablation, the predictor being a pre-ablation nadir temperature, and wherein the pre-ablation nadir temperature is approximately greater than about 6 ℃, and the single freeze-isolation PVI success rate is approximately at least about 90%.

28. The method of claim 19, wherein the characteristic is a predictor of the single freeze-isolated PVI success rate prior to ablation, the predictor being a pre-ablation initial impedance variation, and wherein the pre-ablation initial impedance variation comprises an optimal range of approximately less than about 20 Ω, and the single freeze-isolated PVI success rate is approximately at least about 88.5%.

29. The method of claim 19, wherein the single freeze-isolation PVI success rate is approximately about 92% when the number of electrodes having an initial impedance deviation from a mean is zero.

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