Investigation of Substrates Associated With the Recurrence of Atrial Fibrillation After PV Cryoablation
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation; Recurrence
Study type: Observational

Summary: 
      The two main mechanisms for atrial fibrillation (AF) recurrence after cryoablation include
      Pulmonary vein (PV) reconnection and the presence of non-PV associated arrhythmic focuses.
      The aim of this study is to investigate the prevalence of each mechanism and if biomarkers
      may be used to predict of these events.

      Eighty patients with paroxysmal or persistent AF will undergo PV isolation with cryoablation
      followed by loop recorder implantation. Patients in whom atrial tachyarrhythmias recur during
      12 months follow-up (outside of the 3-month post procedure blanking window) will be offered a
      second electrophysiology study (EP) study to assess PV isolation and non-PV focuses and
      further ablation performed as required.

      At baseline blood samples will be taken to investigate the correlation between specific
      biomarkers and both the incidence and type of recurrence. The correlation between recurrence
      of atrial tachyarrhythmias due to non-PV associated arrhythmic focuses and elevated baseline
      levels of NT-ProBNP, CRP, TNF, MMP1 will be pre-specified.

      40 consecutive patients will have a biopsy taken from the intraventricular and interatrial
      septum to investigate the correlation between myocardial inflammation, the presence of
      fibrosis and recurrence of atrial tachyarrhythmias. Correlation between biomarkers of
      inflammation and biopsy-proven myocardial inflammation or fibrosis will be assessed.
    

Detailed description: 
      The two main mechanisms for atrial fibrillation (AF) recurrence after cryoablation include
      Pulmonary vein (PV) reconnection and the presence of non-PV associated arrhythmic focuses.
      The aim of this study is to investigate the prevalence of each mechanism and if biomarkers
      may be used to predict these events.

      Eighty patients with paroxysmal or persistent AF will undergo PV isolation with cryoablation
      followed by loop recorder implantation. Patients in whom atrial tachyarrhythmias recur during
      12 months follow-up (outside of the 3-month post procedure blanking window) will be offered a
      second EP study to assess PV isolation and non-PV focuses and further ablation performed as
      required. Recurrence will be defined as an episode of atrial tachyarrhythmia (AF, atypical
      atrial flutter, or atrial tachycardia) on loop recorder with a duration greater than 30
      seconds or ECG document atrial tachyarrhythmia. The incidence of atrial tachyarrhythmia
      recurrence, and its association with symptoms after the index PV cryoballoon isolation, will
      be assessed.

      At baseline blood samples will be taken to assess levels of N-terminal pro brain natriuretic
      peptide (NT-proBNP), High-sensitivity C-reactive protein (high-sensitive CRP), Tumor Necrosis
      Factor (TNF), Interleukin 1 beta (IL1B), Fatty acid binding protein (FABP), Matrix
      metalloproteinase-1 (MMP1), Matrix metalloproteinase-3 (MMP3), Matrix metalloproteinase-9
      (MMP9), Transforming growth factor beta 1 (TGF-beta1), Tissue inhibitor of metalloproteinases
      1 (TIMP-1), Fibroblast growth factor 9 (FGF-9). Correlation between recurrence of atrial
      tachyarrhythmias due to non-PV associated arrhythmic focuses and elevated baseline levels of
      NT-ProBNP, CRP, TNF, MMP1 will be pre-specified. We will look with receiver operating
      characteristic (ROC) curve analysis the level of biomarkers which predict recurrence of
      atrial tachyarrhythmias with the best ratio between sensitivity and specificity.

      40 consecutive patients will have a biopsy taken from the intraventricular and interatrial
      septum to investigate the correlation between myocardial inflammation, the presence of
      fibrosis and recurrence of atrial tachyarrhythmias. Correlation between biomarkers of
      inflammation and biopsy-proven myocardial inflammation or fibrosis will be assessed.
    

Intervention name(s): Cryoablation of the pulmonary veins and myocardial biopsy
Intervention type(s): Procedure
Intervention description(s): Before intervention blood samples will be collected for biobank storage. After left atrial appendage thrombus exclusion, a cardiac biopsy from intraventricular and interatrial septum will be performed. PV isolation will be performed with cryoablation. Successful PV isolation will be confirmed by the confirmation of bi-directional block. Phrenic nerve function will be assessed in a standard fashion during intervention of the right PVs using high output phrenic nerve pacing from the superior vena cava. Loop recorder implantation will be performed during the same procedure.
In patients with recurrent atrial tachyarrhythmias an EP study will be performed to assess the mechanism of recurrence. PV reconnections will be re-isolated and linear lesions performed as required.
Other intervention name(s): loop recorder implantation
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients 18-80 years old with symptomatic paroxismal or persistant atrial fibrillation
        (EHRA scale 2b-4)
      
Biospecimen description: 
      Before intervention blood samples will be collected for biobank storage. It is planned to
      assess levels of NT-proBNP, high-sensitive CRP, TNF, IL1B, FABP, MMP1, MMP3, MMP9, TGF-beta1,
      TIMP-1, FGF-9.
    
Keywords: Cryoballoon, Cryoablation, biobanking, Loop recorder, biopsy