PV Cryoablation Efficacy (COR ADVANCE Study)
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional

Summary: 
      The COR advance study is a non-randomized prospective single center study to assess the
      results of an electrophysiologically guided approach for PV cryoablation using the Arctic
      Front Advance ST® catheter together with the Achieve® mapping catheter in 25 patients with
      drug-refractory paroxysmal AF.

      Methods Patient selection criteria will be the same that in the original COR study. All
      patients will be followed with a Reveal LINQ® cardiac monitor that will be implanted before
      ablation. The primary objective is the proportion of patients remaining free from atrial
      fibrillation recurrences without taking antiarrhythmic drugs 12 months after ablation.
      Secondary objectives are: AF-free survival without anti arrhythmic drugs 12 months after
      ablation, cumulative AF burden (number of AF episodes and percentage of time in AF) 12 months
      after ablation, percentage of the pulmonary veins with bidirectional block at the end of the
      procedure, and ablation time (from the onset of the first energy delivery to the end of the
      last energy delivery), procedure time (from femoral puncture to catheter removal), and
      fluoroscopy time.

      Final results will be known 24 months after the first enrollment. Statistical analysis
      Continuous variables that are distributed normally according to the Shapiro-Wilk test will be
      presented as the mean [standard deviation], and the values will be compared with the t test.
      Continuous variables that do not follow a normal distribution will be presented as the median
      [25th to 75th percentile] and will be compared with the Mann-Whitney U test. Categorical
      variables between two groups with expected values <5 will be compared with the Fisher exact
      test. Otherwise, categorical variables will be compared with the chi-squared test. The
      AF-free survival functions will be represented as Kaplan-Meier curves. Data analyses will be
      done with JMP® (version 9.0.1, SAS Institute Inc., Cary, NC, USA) and Stata® (version 11.0,
      StataCorp LP; College Station, TX, USA).
    

Detailed description: 
      Background The Cryoenergy Or Radiofrequency [COR] trial is a randomized, single-center study
      that compared the efficacy of a anatomical simplified strategy for pulmonary vein cryoballoon
      ablation (2 shots per PV, 1 first-generation Arctic Front® catheter per patient and no
      additional touch-up applications to close residual gaps) versus the standard technique for
      pulmonary vein isolation using open-irrigated radiofrequency catheters (Navistar Thermocool®)
      with electrophysiological (Lasso®) and electroanatomical guidance (Carto 3®) in 50 patients
      with drug-refractory paroxysmal atrial fibrillation. All patients were followed with an
      implantable cardiac monitor (Reveal XT®).

      The primary endpoint of the study (proportion of patients remaining free from atrial
      fibrillation recurrences without taking antiarrhythmic drugs 12 months after ablation) was
      met by 48% of patients treated with cryoenergy and 68% of patients treated with
      radiofrequency (OR 0.43 [95% confidence interval, 0.19 to 1.0]; P=0.05). This difference
      disappeared after adjustment for acute procedural outcome. In patients for whom all 4 PVs
      were blocked at the end of the procedure, there was no difference between group C and group R
      in the primary endpoint (67% versus 68%; P=0.94). Thus, the COR trial supports that: 1)
      complete PV conduction block is critical to the success of AF ablation; 2) despite the fact
      that the results of the anatomical cryoablation technique used in the COR study are superior
      to the previously published series of patients treated with PV cryoablation and followed by
      implantable monitors, results of cryoablation might be even better if we aim for PV
      conduction block. At present time, the availability of the Achieve® mapping catheter and the
      more efficient 2nd-generation cryoballoon ArcticFront Advance® catheter provides an
      opportunity to test a electrophysiologically guided PV cryoablation approach against
      conventional PV isolation with point-by-point radiofrequency ablation catheters.

      The COR advance study is a non-randomized observational prospective single center study to
      assess the results of an electrophysiologically guided approach for PV cryoablation using the
      Arctic Front Advance ST® catheter together with the Achieve® mapping catheter in 25 patients
      with drug-refractory paroxysmal AF.

      Methods

      Inclusion criteria:

        -  Symptomatic recurrent paroxysmal AF

        -  >2 episodes in the last 6 months

        -  Refractory to 1 or more antiarrhythmic drugs

        -  Anatomical pattern consisting of 4 pulmonary veins

        -  Willing and capable of providing informed consent

      Exclusion criteria:

        -  Patients that are <18 or >75 years old

        -  Prior AF ablation

        -  Prior cardiac surgery

        -  Moderate to severe valvular heart disease

        -  Anteroposterior diameter of the left atrium >50 mm

        -  Hyperthyroidism, intracardiac thrombus, contraindications for anticoagulation,
           concomitant acute illness, pregnancy.

        -  Unavailability for follow-up at our center for at least 1 year

      All procedures will be performed in the Arrhythmia Unit of our Institution. Patients will
      need to give written informed consent to be enrolled in this study. Pre-procedural exams and
      pre-ablation technique will be the same that used in the COR trial. The end point of PV
      cryoablation will be complete bidirectional PV conduction block assessed with the Achieve®
      catheter. Only one ArcticFront Advance® or ArcticFront Advance ST® catheter (23 or 28 mm
      diameter) will be used per patient. Every cryoenergy delivery will last 240 seconds, except
      in case of excessive freezing (temperature ≤-65ºC with a 23 mm balloon or ≤-60º with a 28 mm
      balloon), diaphragmatic hypokinesia or other significant adverse event related to freezing.
      No bonus applications will be given if the time to effect is less than 60 seconds with a
      23-mm cryoballoon catheter, or less than 90 seconds with a 28-mm cryoballoon. When the time
      to effect cannot be assessed, no bonus applications will be given provided that there is
      complete occlusion of the PV during freezing (persistent contrast staining of the PV) and the
      application results in PV conduction block. Otherwise, either late PV conduction block or
      incomplete PV occlusion during freezing will need a bonus cryoenergy delivery. If PV
      conduction block is not achieved, one or more additional cryoenergy applications will be
      given at discretion of the responsible physician. Thus, the number of cryoenergy applications
      will not be limited by protocol, but the use of a different size cryoballoon or conventional
      point-by-point ablation catheters is strongly discouraged.

      Patient selection criteria will be the same that in the original COR study. All patients will
      be followed with a Reveal LINQ® cardiac monitor that will be implanted before ablation. The
      primary objective is the proportion of patients remaining free from atrial fibrillation
      recurrences without taking antiarrhythmic drugs 12 months after ablation. Secondary
      objectives are: AF-free survival without anti arrhythmic drugs 12 months after ablation,
      cumulative AF burden (number of AF episodes and percentage of time in AF) 12 months after
      ablation, percentage of the pulmonary veins with bidirectional block at the end of the
      procedure, and ablation time (from the onset of the first energy delivery to the end of the
      last energy delivery), procedure time (from femoral puncture to catheter removal), and
      fluoroscopy time.

      Final results will be known 24 months after the first enrollment.

      Statistical analysis Continuous variables that are distributed normally according to the
      Shapiro-Wilk test will be presented as the mean [standard deviation], and the values will be
      compared with the t test. Continuous variables that do not follow a normal distribution will
      be presented as the median [25th to 75th percentile] and will be compared with the
      Mann-Whitney U test. Categorical variables between two groups with expected values <5 will be
      compared with the Fisher exact test. Otherwise, categorical variables will be compared with
      the chi-squared test. The AF-free survival functions will be represented as Kaplan-Meier
      curves. Data analyses will be done with JMP® (version 9.0.1, SAS Institute Inc., Cary, NC,
      USA) and Stata® (version 11.0, StataCorp LP; College Station, TX, USA).
    

Intervention name(s): ArticFont Advance ST Cryoenergy Balloon Catheter
Intervention type(s): Device
Intervention description(s): PV isolation using the ArticFont Advance ST Cryoenergy Balloon Catheter
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: atrial fibrillation; catheter ablation; pulmonary vein; cryoenergy; cryoablation; ArcticFront