Calcium Handling and Epicardial Ablation
Condition: Persistent Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional

Summary: 
      In this multi centre prospective study authors will evaluate atrial fibrillation (AF)
      recurrence at 360 days follow-up and calcium handling in patients treated by epicardial
      thoracoscopic ablation for persistent AF. Indeed, responders patients to epicardial ablation
      will experience sinus rhythm restoration after the treatment, and will be in sinus rhythm
      until follow-up end.

      However, from October 2014 to June 2016, 27 consecutive patients with persistent AF will be
      identified and screened for participation in this prospective, multicenter trial at Catholic
      University of Sacred Heart, Campobasso, at University Study of Molise, Campobasso, at Vecchio
      Pellegrini Hospital, Naples and at University of Campania "Luigi Vanvitelli", Naples, Italy.
      All patients will receive an epicardial thoracoscopic pulmonary vein isolation. Before
      interventions, baseline laboratory studies, B type Natriuretic Peptide (BNP) and serum
      Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) will be evaluated. These markers
      will be re-evaluated at 12th month of follow-up.

      Therefore, study hypothesis will be that successful epicardial ablation might reduce, in
      responders patients, the SERCA expression. Parallely, a lower serum expression of SERCA in
      patients with persistent AF might potentially identify a response to an epicardial ablative
      approach, and an innovative target to improve the response to an epicardial ablative
      treatment.
    

Detailed description: 
      Atrial fibrillation (AF) is most common arrhythmia in the worldwide population, and it is
      defined as paroxysmal, persistent and/or permanent. Patients with persistent AF might have
      higher rate of tromboembolic stroke, heart failure events and worse prognosis. Therefore, for
      patients with persistent AF the sinus rhythm restoration by catheter ablation might be a
      valid treatment to ameliorate clinical outcomes. On other hand, in patients with persistent
      AF the catheter ablation by percutaneous approach has a success rate about the 50% at 5 years
      of follow-up. Indeed, the endocardial ablation cannot determine deeper and extensive trans
      mural lesions in pulmonary veins and left atrium structure, and this might favor atrial
      fibrosis and remodeling with consequent persistence of arrhythmic substrate. In this setting,
      the epicardial AF ablation has been proposed to reach epicardial gaps of the complex
      arrhythmic atrial substrate, and this might favor sinus rhythm restoration with consequent
      reduction of the left atrial diameters and volume in patients with persistent AF. Notably,
      40% of patients treated by epicardial ablatiion might show an AF recurrence at follow-up.
      This might be explained by multiple ionic, molecular and cellular alterations favoring AF
      persistence. In this setting, recently a great interest has been focused to study the calcium
      handling as cause of abnormal trigger activity and reentry in AF patients, that are both
      mechanisms implied in the genesis and perpetuation of persistent AF. Intriguingly, patients
      with persistent AF have an over activity of the Sarcoplasmic Endoplasmic Reticulum (SR) with
      increased calcium (Ca2+) release. However, in human atrial myocites the Ca2+ overload causes
      an increased prevalence of spontaneous events and delayed after depolarizations (DADs), (12).
      Therefore, the SERCA over activity increases the risk of Ca overload and this might be
      arrhythmogenic (13). Therefore, abnormal Ca2+ signaling and enhanced diastolic SR Ca2+ leak
      along with cellular DAD-mediated triggered activity might promote AF persistence, than
      favoring electrical and anatomical reentry. Conversely, the persistence of abnormal Ca2+
      signaling and enhanced diastolic SR Ca2+ leak can activate ion channels and trigger
      Ca2+-dependent signaling pathways, thereby promoting the evolution of atrial remodeling and
      the progression of AF to more persistent forms. In this setting, authors might speculate that
      these AF-related alterations in Ca2+ handling and SERCA over activity might contribute to AF
      persistence after an epicardial ablation. Intriguingly, no data have been reported about the
      SERCA activity in patients with persistent AF before and after epicardial ablation. Moreover,
      authors study hypothesis is that a SERCA over expression might be linked to higher rate of
      failure to an epicardial ablation for patients with persistent AF. Thereafter, in this study
      authors will evaluate AF recurrences during 1 year of follow-up after epicardial ablation,
      correlating this clinical outcomes to SERCA protein modifications in patients with sinus
      rhythm restoration (responders group), vs. atrial fibrillating patients (non responders
      group) after an epicardial ablative approach.
    

Intervention name(s): epicardial ablation
Intervention type(s): Procedure
Intervention description(s): In general anesthesia and left lung ventilation, authors will access the right thorax by three working ports. However, a rigid video thoracoscopic camera with a direct optics will be used. Pericardium will be widely opened anterior to a phrenic nerve and transverse and oblique sinuses were dissected. An insertion of the ablation catheter will be a tricky part of the surgery with the first MW catheter, while no special introducer will be provided. Later RF devices will be equipped with a special flexible introducers, lately also with a magnetic tip and the positioning of the catheter around PVs became much safer and easier.
The correct position of catheter will be visualized by trans esophageal echocardiography before the ablation.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment