Clinical trial NCT03587181: Investigation of Substrates Associated With the Recurrence of Atrial Fibrillation After PV Cryoablation
Official title: Investigation of Substrates Associated With the Recurrence of Atrial Fibrillation After PV Cryoablation
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Fibrillation
Keywords: Cryoballoon, Cryoablation, biobanking, Loop recorder, biopsy
Lead sponsor: National Medical Research Center for Therapy and Preventive Medicine
Sponsor class: OTHER_GOV
Collaborators: name: I.M. Sechenov First Moscow State Medical University
First posted: 2018-07-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
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)

Brief 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.

Eligibility criteria: Inclusion Criteria:

• Patient with paroxysmal/persistent atrial fibrillation (EHRA scale 2b-4)

Exclusion Criteria:

* prior interventions for AF
* permanent AF
* contraindications to oral anticoagulation or heparin
* chronic kidney disease requiring dialysis
* untreated hypo- or hyperthyroidism
* breast feeding
* pregnancy
* chronic kidney disease requiring dialysis
* decompensated heart failure
* stroke within the last 3 months
* myocardial infarction within the last 3 months
* Percutaneous coronary intervention or Coronary Artery Bypass Grafting within the last 3 months
* active myocarditis
* artificial valve replacement surgery
* severe mitral or aortic stenosis
* coronary artery disease requiring revascularization
* heart transplant

Primary outcomes:
measure: Atrial tachyarrhythmia recurrence
timeFrame: 1 year
Secondary outcomes:
measure: The prevalence of PV reconnection and non-PV focuses as substrate of atrial tachyarrhythmia after cryoablation
timeFrame: 1 year
measure: The difference in baseline NT-ProBNP levels between those patients with recurrence of atrial tachyarrhythmias due to non-PV associated arrhythmic focuses and those without at 12 months
timeFrame: 1 year
measure: The difference in baseline CRP levels between those patients with recurrence of atrial tachyarrhythmias due to non-PV associated arrhythmic focuses and those without at 12 months
timeFrame: 1 year
measure: The difference in baseline TNF levels between those patients with recurrence of atrial tachyarrhythmias due to non-PV associated arrhythmic focuses and those without at 12 months
timeFrame: 1 year
measure: The difference in baseline MMP1 levels between those patients with recurrence of atrial tachyarrhythmias due to non-PV associated arrhythmic focuses and those without at 12 months
timeFrame: 1 year
measure: The difference in baseline NT-ProBNP levels between those patients with recurrence of atrial tachyarrhythmias and those without at 12 months
timeFrame: 1 year
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: National Research Center for Preventive Medicine
Study officials:
References: