Investigation of Substrates Associated With the Recurrence of Atrial Fibrillation After PV Cryoablation (SubstrateAF)

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.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Procedure: Cryoablation of the pulmonary veins and myocardial biopsy

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.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 101990
    • National Research Center for Preventive Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients 18-80 years old with symptomatic paroxismal or persistant atrial fibrillation (EHRA scale 2b-4)

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Atrial tachyarrhythmia recurrence	Atrial tachyarrhythmias recurrence by ECG, Holter monitoring or loop recorder after 3 months of blanking period	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The prevalence of PV reconnection and non-PV focuses as substrate of atrial tachyarrhythmia after cryoablation	1 year
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	1 year
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	1 year
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	1 year
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	1 year
The difference in baseline NT-ProBNP levels between those patients with recurrence of atrial tachyarrhythmias and those without at 12 months	1 year

Collaborators and Investigators

• Sponsor: National Research Center for Preventive Medicine
• Collaborators: I.M. Sechenov First Moscow State Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2017
• Primary Completion (Actual): October 30, 2019
• Study Completion (Actual): October 30, 2019

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 16, 2018

Study Record Updates

• Last Update Posted (Actual): January 13, 2020
• Last Update Submitted That Met QC Criteria: January 10, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Keywords: Cryoballoon, Cryoablation, biobanking, Loop recorder, biopsy
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Recurrence
• Other Study ID Numbers: 01-04/18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No