Changes in Cardiac Autonomic Nervous System Following Atrial Fibrillation Ablation.

NCT ID: NCT03811639

Last Updated: 2021-02-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

126 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-01

Study Completion Date

2019-12-31

Brief Summary

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Aim. To compare changes in cardiac autonomic tone caused by radio-frequency versus cryoballoon ablation and to assess their value in predicting the outcome.

Study group. In this prospective randomized study 126 consecutive patients with paroxysmal AF undergoing first ablation of AF using radio-frequency (RF) or cryoballoon (CB) technique will be recruited. Patients will undergo several ECG and autonomic tests before and after the procedure. The follow-up will last one year.

Measurements:

1. Standard 12-lead ECG a day before and 1-2 days after the procedure will be performed. The SR and P wave duration as well as the difference (∆) in SR and P wave duration before and after ablation will be analyzed.
2. A 24-hour Holter ECG will be performed at baseline (1-2 days before ablation) and 7-day Holter ECG will be performed 3, 6 and 12 months after the procedure. Minimal, maximal and mean heart rate (HR) as well as HRV parameters will be analyzed. The differences (∆) in these variables between baseline and post-ablation Holter ECG recordings will be analyzed.
3. Autonomic parameters (HR, HRV parameters and baroreceptor reflex sensitivity as well as hemodynamic parameters (stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR)) will be also examined before and after orthostatic stress. This will be performed using tilt table test and non-invasive measurement of autonomic and hemodynamic parameters before and shortly after (1-3 days) the procedure.
4. Quality of life will be assessed using the AFSS scale and EHRA scale at baseline and 3, 6 and 12 months after ablation.
5. Follow-up will last 12 months. Efficacy of ablation will be assessed during outpatients visits and using 7-day Holter ECG recordings 3, 6 and 12 months after the procedure. The analyzed outcomes will include symptomatic recurrences of AF, hospitalizations due to AF, redo procedures i occurrence of asymptomatic AF on Holter ECG monitoring.
6. All the above listed parameters and ablation efficacy will be compared between the RF and CB groups.

Anticipated results.

1. Ablation significantly effects the parameters of cardiac autonomic control
2. These effects are more pronounced in the CB group compared with the RF group
3. Changes in autonomic indices have value in predicting ablation efficacy in both analyzed groups.

Detailed Description

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ABLation-induced changes in cardiac Autonomic Nervous System in patients with Atrial Fibrillation: radiofrequency versus cryoballoon techniques (the ABLANSAF study).

Introduction. The primary goal of ablation for atrial fibrillation (AF) is pulmonary vein isolation (PVI). The second mechanism of action of ablation is modification of cardiac autonomic tone by ablation of atrial ganglionated plexi, mainly of their parasympathetic component. Data in literature concerning this topic is scares. A few studies showed that ablation-induced changes in heart rate variability (HRV) or sinus rate (SR) predict the outcome. However, these data are preliminary and have not yet been included into clinical practice. Moreover, whether these effects depend on the technique used - radio-frequency (RF) ablation or cryoballoon (CB) ablation, has not yet been examined.

Aim. To compare the changes in cardiac autonomic tone caused by RF versus CB ablation and to assess their value in predicting the outcome after the procedure.

Hypothesis. We hypothesised that both techniques cause significant changes in cardiac autonomic innervation, however, these changes are significantly more pronounced following CB rather than RF ablation.

Methods. Study group. In this prospective randomised study 126 consecutive patients with paroxysmal AF undergoing first ablation of AF using RF or CB technique will be recruited. Patients will undergo several ECG and autonomic tests before and after the procedure. The follow-up will last one year.

Ablation The RF and CB ablation will be performed using standard approach. A patient will be randomly selected to RF or CB ablation. The only parameter influencing randomisation will be the presence of the common trunk of the left PV (visualised by computed tomography or rotational angiography) which is regarded as relative contraindication to CB because of anatomical difficulties in the positioning of balloon. In such cases the decision as to the type of procedure will be left to the discretion of the operator.

The CB PVI will be conducted in standard manner. Briefly, after injection of local anesthetic, both femoral veins is punctured. One long sheath (8.5 F Swartz, St. Jude, Saint Paul, USA) to cross interatrial septum is inserted in the right femoral vein. Another two short sheaths were inserted in the left femoral vein for the intracardiac echocardiographic probe (8 or 10 Fr Acunav, Acuson, Siemens, Berlin) and diagnostic catheter introduced into the coronary sinus. After crossing the septum and introducing guidewire into the left superior pulmonary vein (LSPV), long sheath is replaced with steerable sheath (14 F., Flexcath, Medtronic, Minneapolis, USA) and CB (28 mm, second generation) is introduced into the left atrium. Next, the Achieve (20 mm diameter) mapping catheter, (Medtronic, Milwaukee, USA) is placed in the LSPV ostium, CB inflated and contrast injected to confirm proper occlusion of LSPV. When PVI is achieved during first freezing lasting 180 - 240 sec and confirmed by PV potentials (PVP) disappearance within 60 seconds by recordings from the Achieve catheter, no second cryoapplication is performed. In case of incomplete occlusion, persistence or very late disappearance of PVP, suboptimal temperatures achieved (less than -36C) or very short thawing time, CB is repositioned and another cryo-application is delivered. Next, CB-PVI of the left inferior pulmonary vein (LIPV), right superior pulmonary vein (RSPV) and right inferior pulmonary vein (RIPV) is performed. Pacing of the right phrenic nerve is performed during CB of the right veins to avoid phrenic nerve palsy.

The RF ablation is performed in a standard manner using 3-D electro-anatomical system CARTO-3 (Biosense Webster, USA) and Smarttouch ablation catheter. Two separate transseptal punctures are performed under intracardiac echocardiography guidance. After reconstruction of the left atrial geometry using merging of the computed tomography or rotational angiography image with the CARTO map, the point-by-point PVI of each vein is performed. The ablation index is used to ensure the quality of RF applications. The Lasso circular catheter (Biosense Webster, USA) is used to assess PVI and diagnostic catheter placed in the coronary sinus is used for pacing manoeuvres.

Measurements:

1. Standard 12-lead ECG a day before and 1-2 days after the procedure will be performed. The SR and P wave duration as well as the difference (∆) in SR and P wave duration before and after ablation will be analysed.
2. A 24-hour Holter ECG will be performed at baseline (1-2 days before ablation) and 7-day Holter ECG will be performed 3, 6 and 12 months after the procedure. Minimal, maximal and mean heart rate (HR) as well as time-domain HRV parameters (SDNN, SDANN, pNN50, rMSSD) and frequency-domain HRV indices (LF, HF, LF/HF) will be analysed. The differences (∆) in these variables between baseline and post-ablation Holter ECG recordings will be analysed.
3. Autonomic parameters (HR, frequency-domain HRV parameters and baro-reflex sensitivity (BRS) using sequential method) as well as hemodynamic parameters (stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR)) will be also examined before and after orthostatic stress. This will be performed using tilt table test (70 degrees) and non-invasive measurement of autonomic and hemodynamic parameters (cardiac impedance method) using the Task Force system, before (1-2 days) and shortly after (1-3 days) the procedure. The 5-min ECG recordings will be used to calculate the values of autonomic and haemodynamic parameters. Also ∆ of these parameters will be computed. The values measured before and after ablation, before and after tilt testing as well ∆ will be compared.
4. Quality of life will be assessed using the AFSS scale and EHRA scale at baseline and 3, 6 and 12 months after ablation.
5. Follow-up will last 12 months. Efficacy of ablation will be assessed during outpatients visits and using 7-day Holter ECG recordings 3, 6 and 12 months after the procedure. The analysed outcomes will include symptomatic recurrences of AF, hospitalisations due to AF, redo procedures i occurrence of asymptomatic AF on Holter ECG monitoring. Efficacy of the procedure will be assessed and defined as (1) complete efficacy - no symptoms attributed to AF and no AF on Holter ECG monitoring; (2) symptomatic efficacy - no symptoms attributed to AF but AF episodes \> 30 sec recorded on Holter ECG monitoring; (3) partial efficacy - recurrences of symptomatic AF, however, of lower intensity, defined as improvement of at least 1 degree in the EHRA scale and improvement in the AFSS scale; and (4) no effects - no change in symptoms compared with the pre-ablation periods.
6. All the above listed parameters and ablation efficacy will be compared between the RF and CB groups.

Statistical analysis. The results will be presented as mean±SD (normally distributed variables) or median values (not normally distributed variables). The changes between baseline and parameters obtained after ablation as well as before and after tilt testing will be performed using paired two-tailed Student t-test, Mann-Whitney or ANOVA tests where appropriate. The results obtained in the RF versus CB groups will be compared using unpaired Student t-test. The predictive value of examined parameters in identifying responders to ablation will be assessed using the ROC curves and by computing sensitivity, specificity, positive and negative predictive value. Multivariate analysis will be performed to identify parameters independently associated with ablation efficacy. A p value \< 0.05 will be considered significant.

The estimated number of patients sufficient to detect significant difference between the RF and CB groups is 126 based on the assumption that ablation-induced changes in cardiac autonomic parameters will differ between the RF and CB groups by 20% (alfa error = 0.05 and beta error = 0.2) Anticipated results.

1. Ablation significantly effects the parameters of cardiac autonomic control
2. These effects are more pronounced in the CB group compared with the RF group
3. Changes in autonomic indices have value in predicting ablation efficacy in both analysed groups.

Conditions

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Atrial Fibrillation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Comparison of changes in autonomic heart regulation caused by radio-frequency ablation and cryoballoon ablation
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RF ablation

Patients treated with point-by-point radio-frequency ablation

Group Type ACTIVE_COMPARATOR

Radio-frequency ablation

Intervention Type PROCEDURE

Ablation for atrial fibrillation

Cryoballoon ablation

Patients treated with cryoballoon ablation

Group Type EXPERIMENTAL

Cryoballoon ablation

Intervention Type PROCEDURE

Ablation for atrial fibrillation

Interventions

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Radio-frequency ablation

Ablation for atrial fibrillation

Intervention Type PROCEDURE

Cryoballoon ablation

Ablation for atrial fibrillation

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Paroxysmal AF
* First AF ablation
* Sinus rhythm before and after the procedure at the time of ECG and tilt table testing.
* No change in medication affecting cardiac autonomic nervous system before and after ablation.
* Obtained written informed consent to participate in the study.

Exclusion Criteria

* Any of inclusion criterion not met
* Pacing system implanted
* Additional ablation to PVI like cavo-tricuspid isthmus ablation or linear lesions in the left atrium.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centre of Postgraduate Medical Education

OTHER

Sponsor Role lead

Responsible Party

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Prof. Piotr Kulakowski

Professor, head of Electrophysiology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Piotr Kulakowski, MD

Role: STUDY_CHAIR

Postgraduate Medical School, Grochowski Hospital

Locations

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Department of Cardiology, Postgraduate Medical School, Grochowski Hospital

Warsaw, , Poland

Site Status

Countries

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Poland

References

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Hsieh MH, Chiou CW, Wen ZC, Wu CH, Tai CT, Tsai CF, Ding YA, Chang MS, Chen SA. Alterations of heart rate variability after radiofrequency catheter ablation of focal atrial fibrillation originating from pulmonary veins. Circulation. 1999 Nov 30;100(22):2237-43. doi: 10.1161/01.cir.100.22.2237.

Reference Type BACKGROUND
PMID: 10577997 (View on PubMed)

Pappone C, Santinelli V, Manguso F, Vicedomini G, Gugliotta F, Augello G, Mazzone P, Tortoriello V, Landoni G, Zangrillo A, Lang C, Tomita T, Mesas C, Mastella E, Alfieri O. Pulmonary vein denervation enhances long-term benefit after circumferential ablation for paroxysmal atrial fibrillation. Circulation. 2004 Jan 27;109(3):327-34. doi: 10.1161/01.CIR.0000112641.16340.C7. Epub 2004 Jan 5.

Reference Type RESULT
PMID: 14707026 (View on PubMed)

Yamada T, Yoshida N, Murakami Y, Okada T, Yoshida Y, Muto M, Inden Y, Murohara T. Vagal modification can be a valid predictor of late recurrence of paroxysmal atrial fibrillation independent of the pulmonary vein isolation technique. Circ J. 2009 Sep;73(9):1606-11. doi: 10.1253/circj.cj-09-0158. Epub 2009 Jul 17.

Reference Type RESULT
PMID: 19609042 (View on PubMed)

Yamada T, Yoshida N, Murakami Y, Okada T, Yoshida Y, Muto M, Inden Y, Murohara T. The difference in autonomic denervation and its effect on atrial fibrillation recurrence between the standard segmental and circumferential pulmonary vein isolation techniques. Europace. 2009 Dec;11(12):1612-9. doi: 10.1093/europace/eup330. Epub 2009 Oct 29.

Reference Type RESULT
PMID: 19875397 (View on PubMed)

Yamaguchi Y, Kumagai K, Nakashima H, Saku K. Long-term effects of box isolation on sympathovagal balance in atrial fibrillation. Circ J. 2010 Jun;74(6):1096-103. doi: 10.1253/circj.cj-09-0899. Epub 2010 May 8.

Reference Type RESULT
PMID: 20467150 (View on PubMed)

Oswald H, Klein G, Koenig T, Luesebrink U, Duncker D, Gardiwal A. Cryoballoon pulmonary vein isolation temporarily modulates the intrinsic cardiac autonomic nervous system. J Interv Card Electrophysiol. 2010 Oct;29(1):57-62. doi: 10.1007/s10840-010-9491-7. Epub 2010 Jun 16.

Reference Type RESULT
PMID: 20556498 (View on PubMed)

Lim PB, Malcolme-Lawes LC, Stuber T, Koa-Wing M, Wright IJ, Tillin T, Sutton R, Davies DW, Peters NS, Francis DP, Kanagaratnam P. Feasibility of multiple short, 40-s, intra-procedural ECG recordings to detect immediate changes in heart rate variability during catheter ablation for arrhythmias. J Interv Card Electrophysiol. 2011 Nov;32(2):163-71. doi: 10.1007/s10840-011-9580-2. Epub 2011 Jun 7.

Reference Type RESULT
PMID: 21647641 (View on PubMed)

Wang K, Chang D, Chu Z, Yang Y, Gao L, Zhang S, Xia Y, Dong Y, Yin X, Cong P, Jia J. Denervation as a common mechanism underlying different pulmonary vein isolation strategies for paroxysmal atrial fibrillation: evidenced by heart rate variability after ablation. ScientificWorldJournal. 2013 Aug 24;2013:569564. doi: 10.1155/2013/569564. eCollection 2013.

Reference Type RESULT
PMID: 24058286 (View on PubMed)

Seaborn GE, Todd K, Michael KA, Baranchuk A, Abdollah H, Simpson CS, Akl SG, Redfearn DP. Heart rate variability and procedural outcome in catheter ablation for atrial fibrillation. Ann Noninvasive Electrocardiol. 2014 Jan;19(1):23-33. doi: 10.1111/anec.12098. Epub 2013 Sep 24.

Reference Type RESULT
PMID: 24112475 (View on PubMed)

Kang KW, Kim TH, Park J, Uhm JS, Joung B, Hwang C, Lee MH, Pak HN. Long-term changes in heart rate variability after radiofrequency catheter ablation for atrial fibrillation: 1-year follow-up study with irrigation tip catheter. J Cardiovasc Electrophysiol. 2014 Jul;25(7):693-700. doi: 10.1111/jce.12398. Epub 2014 Mar 28.

Reference Type RESULT
PMID: 24575794 (View on PubMed)

Mori H, Kato R, Ikeda Y, Goto K, Tanaka S, Asano S, Shiki Y, Nagase T, Iwanaga S, Nishimura S, Muramatsu T, Matsumoto K. Analysis of the heart rate variability during cryoballoon ablation of atrial fibrillation. Europace. 2018 Aug 1;20(8):1259-1267. doi: 10.1093/europace/eux225.

Reference Type RESULT
PMID: 29016780 (View on PubMed)

Yu HT, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Pak HN. Prognosis of high sinus heart rate after catheter ablation for atrial fibrillation. Europace. 2017 Jul 1;19(7):1132-1139. doi: 10.1093/europace/euw142.

Reference Type RESULT
PMID: 27256421 (View on PubMed)

Other Identifiers

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65/PB/2015

Identifier Type: -

Identifier Source: org_study_id

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