<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04466358</url>
  </required_header>
  <id_info>
    <org_study_id>CLOSEVSHD</org_study_id>
    <nct_id>NCT04466358</nct_id>
  </id_info>
  <brief_title>CLOSE Versus High Density Mapping Guided Catheter Ablation of Paroxysmal Atrial Fibrillation</brief_title>
  <official_title>Comparison of CLOSE Guided and High Density Mapping Guided Catheter Ablation of Paroxysmal Atrial Fibrillation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medical Centre Ljubljana</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medical Centre Ljubljana</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to compare two methods of catheter ablation for treatment of&#xD;
      paroxysmal atrial fibrillation (AF). The first method being a modified CLOSE protocol used&#xD;
      for the control group and the second high density mapping guided isolation of pulmonary veins&#xD;
      used for the interventional group. Comparison will be made according to clinical parameters&#xD;
      and also durability of pulmonary vein isolation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CLOSE protocol is among the latest methods of catheter ablation of AF. According to this&#xD;
      protocol, ablations are guided by ablation index, which takes into account ablation time, the&#xD;
      contact force and power supplied by the ablation catheter. In this protocol the distance&#xD;
      between individual ablation lesions is less than 6 millimeters (mm), thus ensuring the&#xD;
      continuity of the ablation line around the pulmonary veins. After ablation, the electrical&#xD;
      isolation of pulmonary veins (entry and exit block) is checked with a multi-electrode&#xD;
      circumferential catheter. The electrical inactivity of the ablation line itself is thus&#xD;
      checked indirectly via the conduction block. According to recent studies, the success rate of&#xD;
      catheter ablation with this protocol after one procedure at one year is approximately 90%.&#xD;
      Investigators believe that the presence of electrical activity within the ablation line,&#xD;
      which does not translate into and out of the pulmonary veins during the procedure and is not&#xD;
      detected by the currently used mapping technique, significantly affects the subsequent&#xD;
      clinical success of the procedure. Investigators assume that high-resolution mapping of the&#xD;
      ablation line would identify areas of electrical activity within the ablation line (dormant&#xD;
      conduction) and that the ablation of these areas during the first procedure would&#xD;
      significantly affect both the long-term isolation of the pulmonary veins and the clinical&#xD;
      success of the procedure.&#xD;
&#xD;
      The aim of this study is to compare long-term clinical efficacy and efficacy of pulmonary&#xD;
      vein isolation of two different methods of catheter ablation for treatment of AF.&#xD;
      Participants will be randomised into two groups. In the first group isolation of pulmonary&#xD;
      veins will be performed following a modified CLOSE protocol, the isolation will be checked&#xD;
      with multipolar circumferential catheter. In the second group the ablation will be performed&#xD;
      with the same method but the isolation of pulmonary veins will be checked with&#xD;
      high-resolution mapping looking for dormant conduction in the pulmonary vein antra.&#xD;
&#xD;
      Hypothesis:&#xD;
&#xD;
      investigators expect that the incidence of the recurrence od AF in the high resolution&#xD;
      mapping group will be lower during clinical follow-up. Investigators also expect that durable&#xD;
      pulmonary vein isolation will be present in higher proportion of participants where high&#xD;
      resolution mapping was performed.&#xD;
&#xD;
      Study protocol:&#xD;
&#xD;
      Participants will be randomized 1:1 into two groups:&#xD;
&#xD;
        1. Wide antral circumferential isolation of the pulmonary veins following modified CLOSE&#xD;
           protocol (1) - ablation index at the posterior side 400, at the anterior side 550;&#xD;
           distance between lesions &lt;6 mm. 30 minutes after the completion of the ablation line,&#xD;
           the isolation of the pulmonary veins is checked by inserting multipolar circular&#xD;
           catheter into each pulmonary vein. In case of electrical activity ablation is added to&#xD;
           close the gap in the line until pulmonary veins are electrically isolated.&#xD;
&#xD;
        2. Wide antral circumferential isolation of the pulmonary veins following modified CLOSE&#xD;
           protocol (1) - ablation index at the posterior side 400, at the anterior side 550;&#xD;
           distance between lesions &lt;6 mm. 30 minutes after the completion of the ablation line,&#xD;
           the isolation of the pulmonary veins is checked by inserting multipolar circular&#xD;
           catheter into each pulmonary vein. Additionally a high density map is created with the&#xD;
           multipolar catheter with at least 1000 mapping points for each pulmonary antrum. Signals&#xD;
           considered to represent gaps in the line: multicomponent intracardiac electrograms&#xD;
           consisting of at least three baseline deviations and/or conduction from vein to the&#xD;
           atrium during pacing beyond ablation line (10 milliAmpers, 1 millisecond) and/or voltage&#xD;
           amplitude inside the ablation line above 0.1 milliVolts. If intracardiac signals after&#xD;
           added ablation on the line persist after additional ablations this region is not&#xD;
           considered a gap in the line. The area of the gap is ablated until electric inactivity&#xD;
           of the pulmonary vein antrum as evidenced with high density remapping.&#xD;
&#xD;
      Investigators will record the characteristics of the areas where gaps will be recorded:&#xD;
      inappropriate drop in impedance during ablation (below 10 Ohms), the parameters of the&#xD;
      contact force of the ablation catheter tip during ablation, interlesion distance,&#xD;
      characteristics of unipolar recordings of intracardiac electrograms from the tip of the&#xD;
      ablation catheter and others.&#xD;
&#xD;
      Twelve (12) months after the procedure, all participants (even without proven atrial&#xD;
      tachyarrhythmia) will undergo a re-intervention to check electrical isolation of the&#xD;
      pulmonary veins and pulmonary vein antra with a multi-electrode mapping catheter and high&#xD;
      density mapping. In case of proven re-isolation of the pulmonary veins or their antra,&#xD;
      investigators will find the location of the gap in the ablation line and add additional&#xD;
      ablation at this location until electrical isolation will be achieved.&#xD;
&#xD;
      Follow-up:&#xD;
&#xD;
      All participants will have continuous electrocardiogram (ECG) monitoring for at least 12&#xD;
      hours after the procedure.&#xD;
&#xD;
      On the day after the procedure following examinations will be performed:&#xD;
&#xD;
        -  12-lead ECG,&#xD;
&#xD;
        -  transthoracic ultrasound of the pericardium,&#xD;
&#xD;
      All participants will be monitored clinically for at least 12 months after the procedure:&#xD;
&#xD;
      After 3 months of blanking period, participants will come for the first outpatient&#xD;
      examination in outpatient clinic of the University Medical Center in Ljubljana. This will be&#xD;
      followed by a second outpatient examination after 6 months and a third outpatient examination&#xD;
      after 12 months of intervention. In case of palpitations participants will be instructed to&#xD;
      come to an earlier examination.&#xD;
&#xD;
      Clinical efficacy of the procedure will be defined as absence of AF episodes longer than 30&#xD;
      seconds detected by 24-hour ECG monitoring. Additionally, episodes of AF detected with event&#xD;
      monitors and symptom driven 12-lead ECG recordings will be considered a recurrence.&#xD;
&#xD;
      On the first and second clinical follow-up (3, 6 months) the following examinations will be&#xD;
      performed:&#xD;
&#xD;
        -  history taking and clinical examination,&#xD;
&#xD;
        -  12-lead ECG recording,&#xD;
&#xD;
        -  24-hour Holter ECG,&#xD;
&#xD;
        -  1 week event monitor with daily 2 minute ECG recordings that will be sent to the&#xD;
           investigator.&#xD;
&#xD;
      On the third clinical follow-up (12 months) the following examinations will be performed:&#xD;
&#xD;
        -  history taking and clinical examination,&#xD;
&#xD;
        -  12-lead ECG recording,&#xD;
&#xD;
        -  24-hour Holter ECG,&#xD;
&#xD;
        -  1 week event monitor with daily 2 minute ECG recordings that will be sent to the&#xD;
           investigator,&#xD;
&#xD;
        -  transthoracic ultrasound of the heart.&#xD;
&#xD;
      Medical management: Antiarrhythmic drug (AAD) and anticoagulation (AC) management will be&#xD;
      directed by the referring physician. Anticoagulation is continued post-procedurally for at&#xD;
      least three months. This continuation of ADDs and AC will be controled by the referring&#xD;
      physician and a predefined protocol for discontinuation will not be provided. Subsequent&#xD;
      interventions including repeat catheter ablation will be directed by the referring physician&#xD;
      and recorded.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 26, 2021</start_date>
  <completion_date type="Anticipated">September 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 1, 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Recurrence of atrial fibrillation</measure>
    <time_frame>3-12 months</time_frame>
    <description>Atrial fibrillation recorded with 12-lead ECG, event monitor or a 30 seconds episode recorded with Holter ECG.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Durability of pulmonary vein isolation</measure>
    <time_frame>12 months</time_frame>
    <description>Presence of gaps in the circumferential ablation line (reconduction of pulmonary veins) as evidenced at predefined remapping procedure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Characteristics of gaps in ablation lines</measure>
    <time_frame>0-12 months</time_frame>
    <description>Characteristics of electrograms and ablation lesions in the areas where gaps in the ablation line will be discovered acutely during high density mapping at index procedure. Also, characteristics of electrograms and ablation lesions in the areas where gaps will be discovered at a remote re-mapping procedure at 12 months after the index procedure</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Adverse events</measure>
    <time_frame>0-1 month</time_frame>
    <description>During and after the procedure and at clinical follow-ups, any serious adverse event will be recorded. Significant adverse events will be defined as all events that endanger the participant's health or prolong hospitalization, or require intervention:&#xD;
Death in hospital&#xD;
Pericardial effusion resulting in tamponade&#xD;
Cerebral insult&#xD;
Pneumonia&#xD;
Phrenic nerve injury&#xD;
Esophageal perforation&#xD;
Cardiac arrest&#xD;
Complete atrioventricular block&#xD;
Vascular intervention and / or surgery&#xD;
Transfusion</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Pulmonary Vein Isolation</condition>
  <arm_group>
    <arm_group_label>Modified CLOSE protocol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Width antral circumferential pulmonary vein isolation guided according to CLOSE protocol, confirmed with multipolar circular mapping catheter.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High density mapping guided pulmonary vein isolation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Width antral circumferential pulmonary vein isolation guided according to CLOSE protocol and confirmed with high density mapping of each pulmonary vein antrum, with additional ablation lesions at sites of gap or dormant conduction.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Modified CLOSE protocol</intervention_name>
    <description>Modified CLOSE protocol guided isolation of pulmonary veins.</description>
    <arm_group_label>Modified CLOSE protocol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>High density mapping guided pulmonary vein isolation</intervention_name>
    <description>Modified CLOSE protocol guided isolation of pulmonary veins with additional ablations at sites of gaps or dormant conduction as evidenced by high density mapping of pulmonary vein antra.</description>
    <arm_group_label>High density mapping guided pulmonary vein isolation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  electrocardiographic evidence of paroxysmal AF in the last six months,&#xD;
&#xD;
          -  unsuccessful treatment with antiarrhythmic drugs or highly symptomatic arrhythmia&#xD;
             episodes (EHRA 3 and 4).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  age over 80 years,&#xD;
&#xD;
          -  greatly enlarged left atrium (ultrasound parasternal diameter more than 50 mm),&#xD;
&#xD;
          -  life expectancy less than one year,&#xD;
&#xD;
          -  acute life-threatening disease,&#xD;
&#xD;
          -  previous heart surgery,&#xD;
&#xD;
          -  severe left or right ventricular dysfunction (LVEF equal or less than 35 %),&#xD;
&#xD;
          -  severe valve failure,&#xD;
&#xD;
          -  presence of a clot in the left atrium,&#xD;
&#xD;
          -  previous atrial fibrillation ablation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jernej Stublar, MSE</last_name>
    <role>Study Director</role>
    <affiliation>University Medical Centre Ljubljana</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Bor Antolic, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University Medical Centre Ljubljana</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UMC Ljubljana</name>
      <address>
        <city>Ljubljana</city>
        <zip>1000</zip>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Slovenia</country>
  </location_countries>
  <reference>
    <citation>Phlips T, Taghji P, El Haddad M, Wolf M, Knecht S, Vandekerckhove Y, Tavernier R, Duytschaever M. Improving procedural and one-year outcome after contact force-guided pulmonary vein isolation: the role of interlesion distance, ablation index, and contact force variability in the 'CLOSE'-protocol. Europace. 2018 Nov 1;20(FI_3):f419-f427. doi: 10.1093/europace/eux376.</citation>
    <PMID>29315411</PMID>
  </reference>
  <reference>
    <citation>Taghji P, El Haddad M, Phlips T, Wolf M, Knecht S, Vandekerckhove Y, Tavernier R, Nakagawa H, Duytschaever M. Evaluation of a Strategy Aiming to Enclose the Pulmonary Veins With Contiguous and Optimized Radiofrequency Lesions in Paroxysmal Atrial Fibrillation: A Pilot Study. JACC Clin Electrophysiol. 2018 Jan;4(1):99-108. doi: 10.1016/j.jacep.2017.06.023. Epub 2017 Sep 27.</citation>
    <PMID>29600792</PMID>
  </reference>
  <reference>
    <citation>Duytschaever M, De Pooter J, Demolder A, El Haddad M, Phlips T, Strisciuglio T, Debonnaire P, Wolf M, Vandekerckhove Y, Knecht S, Tavernier R. Long-term impact of catheter ablation on arrhythmia burden in low-risk patients with paroxysmal atrial fibrillation: The CLOSE to CURE study. Heart Rhythm. 2020 Apr;17(4):535-543. doi: 10.1016/j.hrthm.2019.11.004. Epub 2019 Nov 9.</citation>
    <PMID>31707159</PMID>
  </reference>
  <reference>
    <citation>Meissner A, Maagh P, Christoph A, Oernek A, Plehn G. Pulmonary vein potential mapping in atrial fibrillation with high density and standard spiral (lasso) catheters: A comparative study. J Arrhythm. 2017 Jun;33(3):192-200. doi: 10.1016/j.joa.2016.10.562. Epub 2016 Nov 25.</citation>
    <PMID>28607614</PMID>
  </reference>
  <reference>
    <citation>Segerson NM, Lynch B, Mozes J, Marks MM, Noonan DK, Gordon D, Jais P, Daccarett M. High-density mapping and ablation of concealed low-voltage activity within pulmonary vein antra results in improved freedom from atrial fibrillation compared to pulmonary vein isolation alone. Heart Rhythm. 2018 Aug;15(8):1158-1164. doi: 10.1016/j.hrthm.2018.04.035. Epub 2018 May 3.</citation>
    <PMID>29729399</PMID>
  </reference>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>August 10, 2023</last_update_submitted>
  <last_update_submitted_qc>August 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Medical Centre Ljubljana</investigator_affiliation>
    <investigator_full_name>Matevz Jan</investigator_full_name>
    <investigator_title>Principal investigator</investigator_title>
  </responsible_party>
  <keyword>pulmonary vein isolation</keyword>
  <keyword>paroxysmal atrial fibrillation</keyword>
  <keyword>high density mapping</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04466358
org study id: CLOSEVSHD
nct id: NCT04466358
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The aim of this study is to compare two methods of catheter ablation for treatment of
      paroxysmal atrial fibrillation (AF). The first method being a modified CLOSE protocol used
      for the control group and the second high density mapping guided isolation of pulmonary veins
      used for the interventional group. Comparison will be made according to clinical parameters
      and also durability of pulmonary vein isolation.
CLOSE protocol is among the latest methods of catheter ablation of AF. According to this
      protocol, ablations are guided by ablation index, which takes into account ablation time, the
      contact force and power supplied by the ablation catheter. In this protocol the distance
      between individual ablation lesions is less than 6 millimeters (mm), thus ensuring the
      continuity of the ablation line around the pulmonary veins. After ablation, the electrical
      isolation of pulmonary veins (entry and exit block) is checked with a multi-electrode
      circumferential catheter. The electrical inactivity of the ablation line itself is thus
      checked indirectly via the conduction block. According to recent studies, the success rate of
      catheter ablation with this protocol after one procedure at one year is approximately 90%.
      Investigators believe that the presence of electrical activity within the ablation line,
      which does not translate into and out of the pulmonary veins during the procedure and is not
      detected by the currently used mapping technique, significantly affects the subsequent
      clinical success of the procedure. Investigators assume that high-resolution mapping of the
      ablation line would identify areas of electrical activity within the ablation line (dormant
      conduction) and that the ablation of these areas during the first procedure would
      significantly affect both the long-term isolation of the pulmonary veins and the clinical
      success of the procedure.

      The aim of this study is to compare long-term clinical efficacy and efficacy of pulmonary
      vein isolation of two different methods of catheter ablation for treatment of AF.
      Participants will be randomised into two groups. In the first group isolation of pulmonary
      veins will be performed following a modified CLOSE protocol, the isolation will be checked
      with multipolar circumferential catheter. In the second group the ablation will be performed
      with the same method but the isolation of pulmonary veins will be checked with
      high-resolution mapping looking for dormant conduction in the pulmonary vein antra.

      Hypothesis:

      investigators expect that the incidence of the recurrence od AF in the high resolution
      mapping group will be lower during clinical follow-up. Investigators also expect that durable
      pulmonary vein isolation will be present in higher proportion of participants where high
      resolution mapping was performed.

      Study protocol:

      Participants will be randomized 1:1 into two groups:

        1. Wide antral circumferential isolation of the pulmonary veins following modified CLOSE
           protocol (1) - ablation index at the posterior side 400, at the anterior side 550;
           distance between lesions <6 mm. 30 minutes after the completion of the ablation line,
           the isolation of the pulmonary veins is checked by inserting multipolar circular
           catheter into each pulmonary vein. In case of electrical activity ablation is added to
           close the gap in the line until pulmonary veins are electrically isolated.

        2. Wide antral circumferential isolation of the pulmonary veins following modified CLOSE
           protocol (1) - ablation index at the posterior side 400, at the anterior side 550;
           distance between lesions <6 mm. 30 minutes after the completion of the ablation line,
           the isolation of the pulmonary veins is checked by inserting multipolar circular
           catheter into each pulmonary vein. Additionally a high density map is created with the
           multipolar catheter with at least 1000 mapping points for each pulmonary antrum. Signals
           considered to represent gaps in the line: multicomponent intracardiac electrograms
           consisting of at least three baseline deviations and/or conduction from vein to the
           atrium during pacing beyond ablation line (10 milliAmpers, 1 millisecond) and/or voltage
           amplitude inside the ablation line above 0.1 milliVolts. If intracardiac signals after
           added ablation on the line persist after additional ablations this region is not
           considered a gap in the line. The area of the gap is ablated until electric inactivity
           of the pulmonary vein antrum as evidenced with high density remapping.

      Investigators will record the characteristics of the areas where gaps will be recorded:
      inappropriate drop in impedance during ablation (below 10 Ohms), the parameters of the
      contact force of the ablation catheter tip during ablation, interlesion distance,
      characteristics of unipolar recordings of intracardiac electrograms from the tip of the
      ablation catheter and others.

      Twelve (12) months after the procedure, all participants (even without proven atrial
      tachyarrhythmia) will undergo a re-intervention to check electrical isolation of the
      pulmonary veins and pulmonary vein antra with a multi-electrode mapping catheter and high
      density mapping. In case of proven re-isolation of the pulmonary veins or their antra,
      investigators will find the location of the gap in the ablation line and add additional
      ablation at this location until electrical isolation will be achieved.

      Follow-up:

      All participants will have continuous electrocardiogram (ECG) monitoring for at least 12
      hours after the procedure.

      On the day after the procedure following examinations will be performed:

        -  12-lead ECG,

        -  transthoracic ultrasound of the pericardium,

      All participants will be monitored clinically for at least 12 months after the procedure:

      After 3 months of blanking period, participants will come for the first outpatient
      examination in outpatient clinic of the University Medical Center in Ljubljana. This will be
      followed by a second outpatient examination after 6 months and a third outpatient examination
      after 12 months of intervention. In case of palpitations participants will be instructed to
      come to an earlier examination.

      Clinical efficacy of the procedure will be defined as absence of AF episodes longer than 30
      seconds detected by 24-hour ECG monitoring. Additionally, episodes of AF detected with event
      monitors and symptom driven 12-lead ECG recordings will be considered a recurrence.

      On the first and second clinical follow-up (3, 6 months) the following examinations will be
      performed:

        -  history taking and clinical examination,

        -  12-lead ECG recording,

        -  24-hour Holter ECG,

        -  1 week event monitor with daily 2 minute ECG recordings that will be sent to the
           investigator.

      On the third clinical follow-up (12 months) the following examinations will be performed:

        -  history taking and clinical examination,

        -  12-lead ECG recording,

        -  24-hour Holter ECG,

        -  1 week event monitor with daily 2 minute ECG recordings that will be sent to the
           investigator,

        -  transthoracic ultrasound of the heart.

      Medical management: Antiarrhythmic drug (AAD) and anticoagulation (AC) management will be
      directed by the referring physician. Anticoagulation is continued post-procedurally for at
      least three months. This continuation of ADDs and AC will be controled by the referring
      physician and a predefined protocol for discontinuation will not be provided. Subsequent
      interventions including repeat catheter ablation will be directed by the referring physician
      and recorded.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recurrence of atrial fibrillation
time frame: 3-12 months
description: Atrial fibrillation recorded with 12-lead ECG, event monitor or a 30 seconds episode recorded with Holter ECG.
measure: Durability of pulmonary vein isolation
time frame: 12 months
description: Presence of gaps in the circumferential ablation line (reconduction of pulmonary veins) as evidenced at predefined remapping procedure.
measure: Characteristics of gaps in ablation lines
time frame: 0-12 months
description: Characteristics of electrograms and ablation lesions in the areas where gaps in the ablation line will be discovered acutely during high density mapping at index procedure. Also, characteristics of electrograms and ablation lesions in the areas where gaps will be discovered at a remote re-mapping procedure at 12 months after the index procedure
measure: Adverse events
time frame: 0-1 month
description: During and after the procedure and at clinical follow-ups, any serious adverse event will be recorded. Significant adverse events will be defined as all events that endanger the participant's health or prolong hospitalization, or require intervention:
Death in hospital
Pericardial effusion resulting in tamponade
Cerebral insult
Pneumonia
Phrenic nerve injury
Esophageal perforation
Cardiac arrest
Complete atrioventricular block
Vascular intervention and / or surgery
Transfusion
arm group label: Modified CLOSE protocol
arm group type: Experimental
description: Width antral circumferential pulmonary vein isolation guided according to CLOSE protocol, confirmed with multipolar circular mapping catheter.
arm group label: High density mapping guided pulmonary vein isolation
arm group type: Active Comparator
description: Width antral circumferential pulmonary vein isolation guided according to CLOSE protocol and confirmed with high density mapping of each pulmonary vein antrum, with additional ablation lesions at sites of gap or dormant conduction.
intervention type: Procedure
intervention name: Modified CLOSE protocol
description: Modified CLOSE protocol guided isolation of pulmonary veins.
arm group label: Modified CLOSE protocol
intervention type: Procedure
intervention name: High density mapping guided pulmonary vein isolation
description: Modified CLOSE protocol guided isolation of pulmonary veins with additional ablations at sites of gaps or dormant conduction as evidenced by high density mapping of pulmonary vein antra.
arm group label: High density mapping guided pulmonary vein isolation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jernej Stublar, MSE
role: Study Director
affiliation: University Medical Centre Ljubljana
last name: Bor Antolic, MD, PhD
role: Study Chair
affiliation: University Medical Centre Ljubljana
facility: 
country: Slovenia
citation: Phlips T, Taghji P, El Haddad M, Wolf M, Knecht S, Vandekerckhove Y, Tavernier R, Duytschaever M. Improving procedural and one-year outcome after contact force-guided pulmonary vein isolation: the role of interlesion distance, ablation index, and contact force variability in the 'CLOSE'-protocol. Europace. 2018 Nov 1;20(FI_3):f419-f427. doi: 10.1093/europace/eux376.
PMID: 29315411
citation: Taghji P, El Haddad M, Phlips T, Wolf M, Knecht S, Vandekerckhove Y, Tavernier R, Nakagawa H, Duytschaever M. Evaluation of a Strategy Aiming to Enclose the Pulmonary Veins With Contiguous and Optimized Radiofrequency Lesions in Paroxysmal Atrial Fibrillation: A Pilot Study. JACC Clin Electrophysiol. 2018 Jan;4(1):99-108. doi: 10.1016/j.jacep.2017.06.023. Epub 2017 Sep 27.
PMID: 29600792
citation: Duytschaever M, De Pooter J, Demolder A, El Haddad M, Phlips T, Strisciuglio T, Debonnaire P, Wolf M, Vandekerckhove Y, Knecht S, Tavernier R. Long-term impact of catheter ablation on arrhythmia burden in low-risk patients with paroxysmal atrial fibrillation: The CLOSE to CURE study. Heart Rhythm. 2020 Apr;17(4):535-543. doi: 10.1016/j.hrthm.2019.11.004. Epub 2019 Nov 9.
PMID: 31707159
citation: Meissner A, Maagh P, Christoph A, Oernek A, Plehn G. Pulmonary vein potential mapping in atrial fibrillation with high density and standard spiral (lasso) catheters: A comparative study. J Arrhythm. 2017 Jun;33(3):192-200. doi: 10.1016/j.joa.2016.10.562. Epub 2016 Nov 25.
PMID: 28607614
citation: Segerson NM, Lynch B, Mozes J, Marks MM, Noonan DK, Gordon D, Jais P, Daccarett M. High-density mapping and ablation of concealed low-voltage activity within pulmonary vein antra results in improved freedom from atrial fibrillation compared to pulmonary vein isolation alone. Heart Rhythm. 2018 Aug;15(8):1158-1164. doi: 10.1016/j.hrthm.2018.04.035. Epub 2018 May 3.
PMID: 29729399
responsible party type: Principal Investigator
investigator affiliation: University Medical Centre Ljubljana
investigator full name: Matevz Jan
investigator title: Principal investigator
mesh term: Atrial Fibrillation
sharing ipd: No