Atrial FibrillationSubstrateAFNCT03587181
Investigation of Substrates Associated With the Recurrence of Atrial Fibrillation After PV Cryoablation
An observational study of Atrial Fibrillation, run by National Research Center for Preventive Medicine at 1 site in Russia.
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Atrial Fibrillation
- What is being tested?
- Cryoablation of the pulmonary veins and myocardial biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 1 siteRussia
- Study dates
- 3 Apr 2017to 30 Oct 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients 18-80 years old with symptomatic paroxismal or persistant atrial fibrillation (EHRA scale 2b-4)
Who may be able to join
- Patient with paroxysmal/persistent atrial fibrillation (EHRA scale 2b-4)
Who cannot join
- prior interventions for AF
- permanent AF
- contraindications to oral anticoagulation or heparin
- chronic kidney disease requiring dialysis
- untreated hypo- or hyperthyroidism
- breast feeding
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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.
Read the 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.
- Conditions
- Atrial Fibrillation
- Being tested
- Cryoablation of the pulmonary veins and myocardial biopsy
- Keywords
- Cryoballoon, Cryoablation, biobanking, Loop recorder, biopsy
- Medical subject headings
- Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cryoablation of the pulmonary veins and myocardial biopsyProcedure or surgery
Also called loop recorder implantation
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Atrial tachyarrhythmia recurrence
Atrial tachyarrhythmias recurrence by ECG, Holter monitoring or loop recorder after 3 months of blanking period
Measured: 1 year
Secondary outcomes (6)
The prevalence of PV reconnection and non-PV focuses as substrate of atrial tachyarrhythmia after cryoablation
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 1 year
The difference in baseline NT-ProBNP levels between those patients with recurrence of atrial tachyarrhythmias and those without at 12 months
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2018
- Study start3 Apr 2017
- Primary completion30 Oct 2019
- Study completion30 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Atrial FibrillationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Research Center for Preventive Medicine
- Sponsor type
- Other government
- Collaborators
- I.M. Sechenov First Moscow State Medical University
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03587181
- Sponsor's protocol ID
- 01-04/18
- Acronym
- SubstrateAF
- Status last verified
- Jan 2020
- First submitted
- 2 Jul 2018
- Last updated
- 13 Jan 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Davtyan K, Topchyan A, Brutyan H, Kalemberg E, Simonyan G, Serdyuk S, Kharlap M, Bazaeva E. Does cryoballoon ablation affect the symptom severity of atrial fibrillation? Insights from 12-months continuous cardiac monitoring. BMC Cardiovasc Disord. 2025 Sep 26;25(1):674. doi: 10.1186/s12872-025-05134-4.
PubMed 41013270
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Substrates Associated With the Recurrence of Atrial Fibrillation After PV Cryoablation
- ClinicalTrials.gov ID
- NCT03587181
- Acronym / sponsor ID
- SubstrateAF / 01-04/18
- Conditions
- Atrial Fibrillation
- Keywords
- Cryoballoon, Cryoablation, biobanking, Loop recorder, biopsy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- National Research Center for Preventive MedicineOther government
- Collaborators
- I.M. Sechenov First Moscow State Medical University
- Study start
- 3 Apr 2017 (actual)
- Primary completion
- 30 Oct 2019 (actual)
- Study completion
- 30 Oct 2019 (actual)
- First posted
- 16 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients 18-80 years old with symptomatic paroxismal or persistant atrial fibrillation (EHRA scale 2b-4)
Key inclusion criteria (1 listed)
- Patient with paroxysmal/persistent atrial fibrillation (EHRA scale 2b-4)
Key exclusion criteria (17 listed)
- prior interventions for AF
- permanent AF
- contraindications to oral anticoagulation or heparin
- chronic kidney disease requiring dialysis
- untreated hypo- or hyperthyroidism
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cryoablation of the pulmonary veins and myocardial biopsyAlso: loop recorder implantationBefore 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. | Procedure or surgery | – |
Primary outcome
Atrial tachyarrhythmia recurrence
Time frame: 1 year
Atrial tachyarrhythmias recurrence by ECG, Holter monitoring or loop recorder after 3 months of blanking period
6 secondary outcomes
The prevalence of PV reconnection and non-PV focuses as substrate of atrial tachyarrhythmia after cryoablation
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 1 year
The difference in baseline NT-ProBNP levels between those patients with recurrence of atrial tachyarrhythmias and those without at 12 months
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Derived from this study: PubMed 41013270Davtyan K, Topchyan A, Brutyan H, Kalemberg E, Simonyan G, Serdyuk S, Kharlap M, Bazaeva E. Does cryoballoon ablation affect the symptom severity of atrial fibrillation? Insights from 12-months continuous cardiac monitoring. BMC Cardiovasc Disord. 2025 Sep 26;25(1):674. doi: 10.1186/s12872-025-05134-4.
- Individual participant dataSharing planned: No
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Atrial Fibrillation (AF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Atrial Fibrillation, run by National Research Center for Preventive Medicine at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Atrial tachyarrhythmia recurrence (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03587181, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2020.