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

Atrial Fibrillation Clinical Trial

— SubstrateAF  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03587181
• Other study ID #: 01-04/18
• Status: Completed
• Start date: April 3, 2017
• Est. completion date: October 30, 2019

Study information

• Verified date: January 2020
• Source: National Research Center for Preventive Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: October 30, 2019
• Est. primary completion date: October 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Recurrence

Intervention

Procedure:
• Cryoablation of the pulmonary veins and myocardial biopsy
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.

Locations

Country	Name	City	State
Russian Federation	National Research Center for Preventive Medicine	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
National Research Center for Preventive Medicine	I.M. Sechenov First Moscow State Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Atrial tachyarrhythmia recurrence	Atrial tachyarrhythmias recurrence by ECG, Holter monitoring or loop recorder after 3 months of blanking period	1 year
Secondary	The prevalence of PV reconnection and non-PV focuses as substrate of atrial tachyarrhythmia after cryoablation		1 year
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	The difference in baseline NT-ProBNP levels between those patients with recurrence of atrial tachyarrhythmias and those without at 12 months		1 year