Comparison of Focal Cryoablation vs. Radiofrequency Cardioneuroablation for Bradyarrhythmias

Official title

Prospective Non-Randomized Comparison of Point-by-Point Cryoablation Using Freezor™ Xtra Versus Radiofrequency Ablation Using TactiFlex™ SE of Parasympathetic Ganglia (Cardioneuroablation) in Patients With Vagally-Mediated Bradyarrhythmias

Overview

Bradyarrhythmias are conditions where the heart beats too slowly, causing symptoms like dizziness, fainting, and fatigue. In some patients, these slow heart rhythms are caused by overactivity of the vagus nerve (the part of the nervous system that slows the heart down). Cardioneuroablation (CNA) is a catheter-based procedure that targets and reduces the effect of these overactive nerves on the heart. It is an alternative to permanent pacemaker implantation, especially for younger patients. Traditionally, CNA is performed using radiofrequency (RF) energy to create small burns in specific areas of the heart. This study investigates whether focal cryoablation (freezing technology using the Freezor™ Xtra catheter) is as safe and effective as standard RF ablation for CNA. This is a prospective, non-randomized study. Participants will receive either RF ablation (N=30) or cryoablation (N=30). The study will evaluate the recurrence of slow heart rhythms and fainting episodes, as well as any complications, over 12 months of follow-up.

Detailed description

Background and Rationale

Cardioneuroablation is an emerging treatment for vagally-mediated bradyarrhythmias, including symptomatic sinus bradycardia, atrioventricular blocks, and vasovagal syncope with a cardioinhibitory component . The procedure targets ganglionated plexi located in the epicardial fat and myocardium, which contain parasympathetic nerve endings.

While radiofrequency (RF) energy is the standard modality for CNA, epicardial fat may limit RF lesion formation when fat thickness exceeds 3 mm. Cryoablation, by contrast, uniformly cools tissue without energy dissipation in fat, potentially offering more consistent ganglion ablation.

To date, no clinical study has compared focal cryoablation versus RF ablation specifically for cardioneuroablation.

Objectives

Primary: To compare the efficacy of focal cryoablation versus RF ablation for cardioneuroablation in preventing bradyarrhythmia recurrence.

Secondary: To compare the safety profile of both techniques, including periprocedural complications and inappropriate sinus tachycardia.

Study Design

This is a prospective, non-randomized, parallel-group study conducted at a single center (Cardiology Research Institute, Tomsk NRMC). Eligible patients aged 18-60 years with symptomatic vagally-mediated bradyarrhythmias (confirmed by positive atropine test and/or EP study) are assigned non-randomly to either:

Group 1 (RF-CNA, N=30): Radiofrequency ablation using TactiFlex™ SE catheter (Abbott), power 45W, target AI 45, with irrigation

Group 2 (Cryo-CNA, N=30): Focal cryoablation using Freezor™ Xtra 6mm catheter (Medtronic), target temperature -75°C, 240 seconds per application

Procedures

All procedures are performed under intravenous sedation. After establishing venous access, a 3D electroanatomical map of the right atrium is created using the EnSite™ X system with HD Grid mapping catheter. Ganglionated plexi are identified using spectral analysis (OTNF algorithm) and anatomical landmarks (RAGP and IRGP).

Ablation is applied at identified sites. Intraprocedural endpoints include:

Reduction of SNRT \<1500 ms and cSNRT \<525 ms

Wenckebach point ≥140 bpm

AV node ERP \>300 ms

Absence of bradycardic response to phenylephrine (\<10% heart rate reduction)

Follow-up

Patients are followed at 6 and 12 months post-procedure with clinical assessment, 12-lead ECG, and 24-hour Holter monitoring.

Statistical Considerations

The planned sample size is 60 patients (30 per group). Quantitative variables will be presented as mean±SD or median \[Q1;Q3\]. Paired t-test or Wilcoxon test will be used for pre-post comparisons. Between-group comparisons will use Mann-Whitney U test. Statistical significance set at p\<0.05.

Interventions

• Procedure Focal Cryoablation
  Focal cryoablation of right atrial ganglionated plexi using Freezor™ Xtra 6mm catheter (Medtronic) at -75°C for 240 seconds per application. 3-5 applications per GP zone. Positioned by fluoroscopy and impedance-based tracking in EnSite™ X system.
• Procedure Radiofrequency Catheter Ablation
  Radiofrequency ablation of right atrial ganglionated plexi using TactiFlex™ SE catheter (Abbott) with power up to 45W, temperature 50°C, target AI 45, with irrigation. 3-5 applications per GP zone. Guided by EnSite™ X mapping system and spectral analysis (OTNF).

Primary outcome measures

• Recurrence of Bradyarrhythmia or Syncope [Time frame: 12 months]

Secondary outcome measures (7)

• Pericardial Effusion or Hemopericardium [Time frame: Periprocedural (7 days)]
• Inappropriate Sinus Tachycardia [Time frame: 12 months]
• Vascular Access Complications [Time frame: Periprocedural (7 days)]
• Change in Minimum Heart Rate [Time frame: Baseline to 6 months]
• Change in Maximum Heart Rate [Time frame: Baseline to 6 months]
• Change in Electrophysiological Parameters [Time frame: Intraprocedural]
• Change in Mean Heart Rate [Time frame: Baseline to 6 months]

Eligibility criteria

Inclusion criteria

• Age 18 to 60 years;
• Symptomatic bradycardia (sinus bradycardia or bradycardia due to atrioventricular block, including transient);
• Severe asymptomatic sinus bradycardia (heart rate less than 30 beats per minute);
• Transient second- or third-degree atrioventricular block;
• Persistent second-degree atrioventricular block;
• Rhythm pauses greater than 6 seconds;
• Recurrent syncope or presyncope with documented association with bradycardia (without trauma);
• Positive response to atropine (heart rate increase ≥25% from baseline or >90 beats per minute) OR positive response to exercise (heart rate increase ≥25% from baseline or >90 beats per minute, OR conversion of second- or third-degree atrioventricular block to first-degree block or complete normalization of atrioventricular conduction during sinus rhythm);

Exclusion criteria

• Chronic antiarrhythmic drug therapy (ongoing);
• Presence of implanted pacemaker, cardiac resynchronization therapy device, or implantable cardioverter-defibrillator;
• Bradyarrhythmia secondary to medications;
• Bradyarrhythmia secondary to electrolyte imbalance (hyperkalemia);
• Bradyarrhythmia secondary to hypothyroidism;
• Bradyarrhythmia secondary to obstructive sleep apnea syndrome;
• Absence of response to pharmacological denervation (no heart rate increase after atropine administration up to maximum dose of 0.2 mg/kg);
• Clinically significant coronary artery disease;
• Post-myocardial infarction cardiosclerosis;
• Hemodynamically significant congenital heart disease (including surgically corrected);
• Stable ventricular tachycardia in the setting of bradycardia;
• History of stroke or transient ischemic attack;
• Prior open-heart surgery;
• Prior catheter-based coronary artery intervention or percutaneous coronary intervention;
• Pregnancy or breastfeeding; Age less than 18 years Age greater than 60 years

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Russia · 1 center

• Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Acade — Tomsk

Identifiers

NCT: NCT07671898 · CRI-281/2

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗