Cardioneuroablation for Reflex Syncope

NCT03903744 | Completed

• 1 other identifier: 113/PB/2018
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

Aim. To assess the effects of cardioneuroablation (CNA) on cardiac autonomic regulation and syncope recurrences in patients with vasovagal syncope (VVS), and to compare this novel approach with standard non-pharmacological treatment. Measurements.

1. 1.Before CNA:
2. 2.Detailed history taking and assessment of eligibility
3. 3.Baseline 12-lead ECG for heart rate assessment, morphology and duration of the P wave and PR interval
4. 4.24-hour Holter ECG for heart rhythm (mean, minimal, maximal, pauses) and heart rate variability (HRV) assessment
5. 5.Passive tilt test (70 degrees, 45 minutes) to fulfill inclusion criterion and to assess baseline autonomic parameters such as HRV and baroreflex sensitivity (BRS) using sequential method. These parameters will be calculated from 5 min recordings before and after orthostatic stress (tilt).
6. 6.Atropine test - positive response to intravenous atropine in a dose of 2 mg defined as at least 30% increase in sinus rate compared with baseline value
7. 7.Assessment of quality of life using the SF-36 questionnaire
8. 8.Implantable Loop Recorder (ILR) implantation 2-3 days before CNA
9. 9.During CNA:
10. 10.Heart rate before and immediately after CNA
11. 11.Episodes of bradycardia (sinus arrest or atrio-ventricular block) during application of RF to GP.
12. 12.Standard electrophysiological parameters (sinus node recovery time, corrected sinus recovery time, refractory atrio-ventricular node, atrio-ventricular conduction - Wenckebach point, A-H and H-V intervals) will be assessed before an immediately after CNA
13. 13.Atropine test (2 mg) will be repeated immediately after CNA.
14. 14.After CNA:
15. 15.1-2 days after CNA standard ECG
16. 16.Follow-up: 3, 12 and 24 months after CNA assessment of symptoms, 12 lead standard ECG, control of ILR, 24-hour Holter ECG, tilt test and atropine test will be performed. Additionally, quality of life will be assessed using SF-36 questionnaire
17. 17.CNA performed with technique used in the present study is effective in \> 90% of patients.
18. 18.CNA-induced changes in analysed ECG and autonomic parameters predict CNA efficacy

Conditions

Syncope, Vasovagal

Keywords

syncope; cardioneuroablation; cardioneuromodulation

Outcome Measures

Primary Outcomes (1)

• Time to first syncope recurrence.

  Recurrence of syncope (in days) after using the appropriate method (cardioneuroablation or standard non-pharmacological treatment).

  Two-year follow-up after starting treatment.

Secondary Outcomes (6)

• Syncope burden.

  Two-year follow-up after starting treatment.

• Presyncope burden.

  Two-year follow-up.

• Heart rate and atrio-ventricular conduction if syncope occurs.

  Two-year follow-up.

• Cardioneuroablation-induced changes in heart rate variability predicting ablation efficacy.

  3, 12 and 24 months after cardioneuroablation.

• Cardioneuroablation-induced changes in baroreflex sensitivity predicting ablation efficacy.

  Two-year follow-up.

Study Arms (2)

Treatment arm

EXPERIMENTAL

Patients treated with cardioneuroablation.

Procedure: Cardioneuroablation

Control arm

ACTIVE COMPARATOR

Patients treated with standard non-pharmacological methods.

Procedure: Cardioneuroablation

Interventions

Cardioneuroablation PROCEDURE

The electroanatomical map of the right (RA) and left (LA) atrium will be created and anatomically-based ablation of GP will be performed. Ablation in the RA is started from the supero-posterior area (superior right atrial GP), to the middle-posterior area (posterior right atrial GP). In the LA, ablation is started at the site of the anterior right GP and is continued downwards along the anterior part of a common vestibulum of the right pulmonary veins (PV), opposite to the right-sided ablation lesions. Finally, area of right inferior GP, close to the RIPV is ablated under intracardiac echocardiography control. Using this technique, GP's located close to the left PV are not ablated. We use a pure anatomic approach without identification of GP.

Also known as: Cardioneuromodulation

Control arm; Treatment arm

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• At least one documented spontaneous VVS during preceding 12 months or one syncope in history leading to injury and minimum 2 presyncopal events during preceding 12 months, refractory to all recommended types of standard treatment.
• In case of lack of ECG documentation during spontaneous syncope and history suggesting reflex syncope, at least 3 seconds of asystole due to sinus arrest or atrio-ventricular block with syncope or bradycardia \<40 beats per minute with syncope or presyncope during baseline tilt test
• Sinus rhythm during ECG and tilt test
• Significantly decreased quality of life due to syncope
• Positive response to atropine test
• Obtained written informed consent.

You may not qualify if:

• Other possible and treatable causes of syncope such as significant cardiac disease, cardiac arrhythmia or abnormalities of vertebro-basiliar arteries
• History of stroke or TIA
• History of cardiac surgery
• Contraindications to ablation in the right or left atrium

Sponsors & Collaborators

• Centre of Postgraduate Medical Education: lead

Study Sites (1)

Department of Cardiology, Postgraduate Medical School, Grochowski Hospital

Warsaw, Masovian Voivodeship, 04-073, Poland

Location

Related Publications (19)

• Brignole M, Moya A, de Lange FJ, Deharo JC, Elliott PM, Fanciulli A, Fedorowski A, Furlan R, Kenny RA, Martin A, Probst V, Reed MJ, Rice CP, Sutton R, Ungar A, van Dijk JG; ESC Scientific Document Group. 2018 ESC Guidelines for the diagnosis and management of syncope. Eur Heart J. 2018 Jun 1;39(21):1883-1948. doi: 10.1093/eurheartj/ehy037. No abstract available.

  PMID: 29562304 RESULT

• Grubb BP. Clinical practice. Neurocardiogenic syncope. N Engl J Med. 2005 Mar 10;352(10):1004-10. doi: 10.1056/NEJMcp042601. No abstract available.

  PMID: 15758011 RESULT

• Mathias CJ, Deguchi K, Schatz I. Observations on recurrent syncope and presyncope in 641 patients. Lancet. 2001 Feb 3;357(9253):348-53. doi: 10.1016/S0140-6736(00)03642-4.

  PMID: 11210997 RESULT

• Sheldon RS, Grubb BP 2nd, Olshansky B, Shen WK, Calkins H, Brignole M, Raj SR, Krahn AD, Morillo CA, Stewart JM, Sutton R, Sandroni P, Friday KJ, Hachul DT, Cohen MI, Lau DH, Mayuga KA, Moak JP, Sandhu RK, Kanjwal K. 2015 heart rhythm society expert consensus statement on the diagnosis and treatment of postural tachycardia syndrome, inappropriate sinus tachycardia, and vasovagal syncope. Heart Rhythm. 2015 Jun;12(6):e41-63. doi: 10.1016/j.hrthm.2015.03.029. Epub 2015 May 14. No abstract available.

  PMID: 25980576 RESULT

• Rose MS, Koshman ML, Spreng S, Sheldon R. The relationship between health-related quality of life and frequency of spells in patients with syncope. J Clin Epidemiol. 2000 Dec;53(12):1209-16. doi: 10.1016/s0895-4356(00)00257-2.

  PMID: 11146266 RESULT

• Bartoletti A, Fabiani P, Bagnoli L, Cappelletti C, Cappellini M, Nappini G, Gianni R, Lavacchi A, Santoro GM. Physical injuries caused by a transient loss of consciousness: main clinical characteristics of patients and diagnostic contribution of carotid sinus massage. Eur Heart J. 2008 Mar;29(5):618-24. doi: 10.1093/eurheartj/ehm563. Epub 2007 Dec 16.

  PMID: 18086659 RESULT

• Chen-Scarabelli C, Scarabelli TM. Neurocardiogenic syncope. BMJ. 2004 Aug 7;329(7461):336-41. doi: 10.1136/bmj.329.7461.336. No abstract available.

  PMID: 15297344 RESULT

• Brignole M, Menozzi C, Moya A, Andresen D, Blanc JJ, Krahn AD, Wieling W, Beiras X, Deharo JC, Russo V, Tomaino M, Sutton R; International Study on Syncope of Uncertain Etiology 3 (ISSUE-3) Investigators. Pacemaker therapy in patients with neurally mediated syncope and documented asystole: Third International Study on Syncope of Uncertain Etiology (ISSUE-3): a randomized trial. Circulation. 2012 May 29;125(21):2566-71. doi: 10.1161/CIRCULATIONAHA.111.082313. Epub 2012 May 7.

  PMID: 22565936 RESULT

• Aydin MA, Mortensen K, Salukhe TV, Wilke I, Ortak M, Drewitz I, Hoffmann B, Mullerleile K, Sultan A, Servatius H, Steven D, von Kodolitsch Y, Meinertz T, Ventura R, Willems S. A standardized education protocol significantly reduces traumatic injuries and syncope recurrence: an observational study in 316 patients with vasovagal syncope. Europace. 2012 Mar;14(3):410-5. doi: 10.1093/europace/eur341. Epub 2011 Nov 1.

  PMID: 22048993 RESULT

• Sheldon RS, Morillo CA, Klingenheben T, Krahn AD, Sheldon A, Rose MS. Age-dependent effect of beta-blockers in preventing vasovagal syncope. Circ Arrhythm Electrophysiol. 2012 Oct;5(5):920-6. doi: 10.1161/CIRCEP.112.974386. Epub 2012 Sep 12.

  PMID: 22972872 RESULT

• Tan MP, Newton JL, Chadwick TJ, Gray JC, Nath S, Parry SW. Home orthostatic training in vasovagal syncope modifies autonomic tone: results of a randomized, placebo-controlled pilot study. Europace. 2010 Feb;12(2):240-6. doi: 10.1093/europace/eup368. Epub 2009 Nov 17.

  PMID: 19919966 RESULT

• Romme JJ, van Dijk N, Go-Schon IK, Reitsma JB, Wieling W. Effectiveness of midodrine treatment in patients with recurrent vasovagal syncope not responding to non-pharmacological treatment (STAND-trial). Europace. 2011 Nov;13(11):1639-47. doi: 10.1093/europace/eur200. Epub 2011 Jul 13.

  PMID: 21752826 RESULT

• Raviele A, Giada F, Menozzi C, Speca G, Orazi S, Gasparini G, Sutton R, Brignole M; Vasovagal Syncope and Pacing Trial Investigators. A randomized, double-blind, placebo-controlled study of permanent cardiac pacing for the treatment of recurrent tilt-induced vasovagal syncope. The vasovagal syncope and pacing trial (SYNPACE). Eur Heart J. 2004 Oct;25(19):1741-8. doi: 10.1016/j.ehj.2004.06.031.

  PMID: 15451153 RESULT

• Yao Y, Shi R, Wong T, Zheng L, Chen W, Yang L, Huang W, Bao J, Zhang S. Endocardial autonomic denervation of the left atrium to treat vasovagal syncope: an early experience in humans. Circ Arrhythm Electrophysiol. 2012 Apr;5(2):279-86. doi: 10.1161/CIRCEP.111.966465. Epub 2012 Jan 24.

  PMID: 22275485 RESULT

• Pachon JC, Pachon EI, Cunha Pachon MZ, Lobo TJ, Pachon JC, Santillana TG. Catheter ablation of severe neurally meditated reflex (neurocardiogenic or vasovagal) syncope: cardioneuroablation long-term results. Europace. 2011 Sep;13(9):1231-42. doi: 10.1093/europace/eur163. Epub 2011 Jun 28.

  PMID: 21712276 RESULT

• Aksu T, Golcuk E, Yalin K, Guler TE, Erden I. Simplified Cardioneuroablation in the Treatment of Reflex Syncope, Functional AV Block, and Sinus Node Dysfunction. Pacing Clin Electrophysiol. 2016 Jan;39(1):42-53. doi: 10.1111/pace.12756. Epub 2015 Oct 26.

  PMID: 26411271 RESULT

• Sun W, Zheng L, Qiao Y, Shi R, Hou B, Wu L, Guo J, Zhang S, Yao Y. Catheter Ablation as a Treatment for Vasovagal Syncope: Long-Term Outcome of Endocardial Autonomic Modification of the Left Atrium. J Am Heart Assoc. 2016 Jul 8;5(7):e003471. doi: 10.1161/JAHA.116.003471.

  PMID: 27402231 RESULT

• Piotrowski R, Baran J, Kulakowski P. Cardioneuroablation using an anatomical approach: a new and promising method for the treatment of cardioinhibitory neurocardiogenic syncope. Kardiol Pol. 2018;76(12):1736-1738. doi: 10.5603/KP.a2018.0200. Epub 2018 Oct 19. No abstract available.

  PMID: 30338504 RESULT

• Piotrowski R, Baran J, Sikorska A, Krynski T, Kulakowski P. Cardioneuroablation for Reflex Syncope: Efficacy and Effects on Autonomic Cardiac Regulation-A Prospective Randomized Trial. JACC Clin Electrophysiol. 2023 Jan;9(1):85-95. doi: 10.1016/j.jacep.2022.08.011. Epub 2022 Aug 28.

  PMID: 36114133 DERIVED

MeSH Terms

Conditions

Syncope, Vasovagal; Syncope

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Unconsciousness; Consciousness Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Piotr Kulakowski, Prof.

  Centre of Postgraduate Medical Education

  STUDY CHAIR

• Roman Piotrowski, MD, PhD

  Centre of Postgraduate Medical Education

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 30, 2019
• First Posted: April 4, 2019
• Study Start: November 1, 2018
• Primary Completion: February 15, 2022
• Study Completion: February 15, 2022
• Last Updated: April 19, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)