Clinical trial NCT05707637: Bipolar Radio-frequency Ablation After Standard Unipolar Approach - Prospective Registry.
Official title: Bipolar Radio-frequency Ablation After Standard Unipolar Approach for Ventricular Arrhythmias Originating From the Base of the Heart. The BiUniVA Prospective Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Ventricular Arrythmia
Keywords: ventricular arrhythmia
unipolar ablation
bipolar ablation
base of the heart
Lead sponsor: Centre of Postgraduate Medical Education
Sponsor class: OTHER
First posted: 2023-02-01
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Consecutive patients with ventricular arrhythmias originating from the base of the heart undergoing first standard unipolar ablation

Brief summary: Treatment of ventricular arrhythmias (VA) originating at the base of the heart may be challenging. Unipolar radio-frequency (RF) ablation is a standard approach to treat VA, however, it fails in 10 to 75% of patients, depending on the localization of VA. The main reason for unipolar ablation failure is the intramural location of the source of VA. In such patients, bipolar ablation may occur effective. However, there are no prospective studies or registries on consecutive patients wilt failed unipolar ablation, therefore, the proportion of candidates for bipolar ablation after failed unipolar approach is not known. Also, invasive electrophysiological parameters associated with successful unipolar and bipolar ablation have not been well established. It has been hypothesised that (1) bipolar ablation fails in 12-75% (mean 30%) of consecutive patients and these patients are candidates for bipolar ablation, (2) local ventricular signal precocity \> 20 ms, unipolar signal without R wave and pace mapping 12/12 predict effective unipolar ablation but not bipolar ablation, (3) morphology of VA from surface ECG can identify patients with possible intramural localization, and (4) successful ablation results in improvement of quality of life (QoL).

Aims:

1. To assess how many patients after failed unipolar ablation need redo procedure with bipolar ablation (primary end-point)
2. To assess which intraprocedural electrophysiological parameters predict success during standard unipolar ablation (secondary endpoint)
3. To assess short term efficacy of bipolar ablation (secondary endpoint)
4. To assess one-month efficacy of bipolar ablation (secondary endpoint)
5. To assess which intraprocedural electrophysiological parameters predict success during redo bipolar ablation (secondary endpoint)
6. To evaluate the performance of ECG-based algorithms in predicting the localization / origin of VA, especially of transmural origin (secondary endpoint)
7. To assess the effects of ablation on QoL (secondary endpoint)Methods. The study group consists of all consecutive patients who underwent unipolar ablation of VA originating from the base of the heart in the Grochowski Hospital and collaborating centres. All these patients are referred to Grochowski Hospital for further follow-up and treatment if needed, including bipolar ablation if initial unipolar approach failed. In all patients acute and one-month efficacy of unipolar and bipolar ablation is assessed.

Detailed description: Treatment of ventricular arrhythmias (VA) originating at the base of the heart may be challenging. Although such sites as right ventricular or left ventricular outflow tracts (RVOT and LVOT) or aortic cusps (AoCusps) are usually easy to access, other VA locations may be difficult to reach. They include arrhythmias originating close to the great cardiac vein (GCV), anterior interventricular vein (AIV) or those coming from above the pulmonary valve (PV). In addition, a significant proportion of these arrhythmias have their source of origin in the mid-myocardium and such sites are difficult to ablate from endocardium or epicardium using standard techniques. It has been estimated that the efficacy of standard unipolar radio-frequency (RF) ablation ranges from 80-90% in patients with typical RVOT arrhythmias to 75% in cases with VA originating from LVOT and as low as 25% in VA coming from the left ventricular (LV) summit.

Unipolar radio-frequency (RF) ablation is a standard approach to treat VA. When it fails, bipolar RF ablation may be an attractive alternative. Using this approach, RF energy travels between the tip of ablation electrode and the tip of another electrode, called return or passive electrode. By proper positioning of the electrodes in two adjacent structures, the site of VA origin may lay between the tips of these electrodes and high density RF current may effectively destroy the tissue responsible for VA. The most frequently used electrode locations for bipolar RF ablation are left pulmonic cusp (LPC), AoCusps, aorto-mitral continuity (AMC) and GCV.

It has been shown in animal model that bipolar ablation causes denser and larger lesions than standard unipolar approach. The lesions are also deeper, more transmural and created without steam pops as compared with unipolar RF ablation. Also, the perpendicular orientation of the electrodes tips as well as irrigated catheters rather than standard catheters are important for bipolar ablation safety and efficacy.

The bipolar approach is usually used when unipolar ablation fails. To date, only case reports and case series have been published showing improved outcome when bipolar ablation was used during redo procedures. However, no prospective registry was performed to establish how many patients with VA originating from the base of the heart require bipolar ablation and which invasive electrophysiological (EP) parameters predict failure of unipolar ablation and the need for bipolar approach. One ongoing registry does include consecutive patients and is heterogenous. In the current guidelines for VT ablation, the bipolar approach is only shortly mentioned as one of new and still experimental approaches. Also the performance of surface ECG criteria to predict intra-mural VA and effects of bipolar ablation of quality of life have not been established.

2. Hypothesis.

1. Unipolar ablation fails in a mean of 30% (12-75% depending on VA site), consecutive patients with VA originating from the base of the heart and these patients are candidates for bipolar ablation.
2. Local ventricular signal precocity \> 20 ms, unipolar signal without R wave and pace mapping 12/12 predict effective unipolar ablation
3. Local signal precocity, unipolar signal and pace mapping do not predict efficacy of bipolar ablation,
4. Morphology of VA from surface ECG can identify patients with possible intramural localization of arrhythmia origin in whom initial unipolar ablation fails
5. Successful ablation results in improvement of quality of life (QoL) 3. Aim.

a. To assess how many patients after failed unipolar ablation need redo procedure with bipolar ablation (primary end-point) b. To assess which intraprocedural electrophysiological parameters predict success during standard unipolar ablation (secondary endpoint) c. To assess acute efficacy of bipolar ablation (secondary endpoint) d. To assess one-month efficacy of bipolar ablation (secondary endpoint) e. To assess which intraprocedural electrophysiological parameters predict success during redo bipolar ablation (secondary endpoint) f. To evaluate the performance of ECG-based algorithms in predicting the localization / origin of VA, especially of transmural origin (secondary endpoint) g. To assess the effects of ablation on QoL (secondary endpoint) Methods. Patients. The study group consists of all consecutive patients who underwent unipolar ablation of VA originating from the base of the heart in the Grochowski Hospital and collaborating centres. All these patients are referred to Grochowski Hospital for further follow-up and treatment if needed, including bipolar ablation if initial unipolar approach failed.

Electrophysiology study During EP study three EP parameters characterizing potential site for RF application are assessed. If surface ECG suggests right-sided focus - RVOT is firstly explored. If ECG suggests left-sided focus AoCusps, LVOT, GCV and possibly AIV are firstly explored. The EP parameters consist of (1) precocity of local V signal measured as a difference between the onset of the surface QRS complex (in lead with the earliest onset) and the onset of local bipolar V signal, and (2) presence or absence of R wave in the unipolar V signal. The third (3) parameter - pace-mapping, is also performed and expressed in the number of surface ECG leads with concordant pace-induced and spontaneous QRS morphology and also expressed in percentage of pace-matching in each lead, using dedicated software (EP Bard Lab System, US).

Unipolar ablation. Patients undergo ablation in light sedation using fentanyl and midazolam. In case of lack of PVC in patients with a history PVC only, isoproterenol infusion is used to facilitate PVC occurrence. In patients who undergo ablation due to VT, programmed ventricular stimulation is used to induce VT and in case of non-inducibility, isoproterenol infusion is used and programmed ventricular stimulation repeated to induce VT. In these patients stimulation is repeated at the end of procedure.

RF applications are performed at site with best EP parameters. If this ablation fails, no further attempts are made unless another site is almost as good as initial one and V signal exceeds surface QRS onset.

Ablation is considered acutely effective if no sVT is induced or \>90% reduction of PVC or abolition of nsVT (in patients with nsVT) is achieved.

Ablation is considered acutely failed if all possible sites of VA are mapped: RVOT, PA, GCV, LVOT, AoCusp, AMC (mapping of AVI is not obligatory if placing of ablation electrode there is not feasible) and after RF applications VA is present or no applications were made (no place with good EP parameters were found).

All procedures are performed using Smarttouch Thermocool catheter, ablation index and electroanatomical Carto® 3 (Biosense Webster, Diamond Bar, CA, USA) 3D mapping system. The Smartablate or nGEN ablators are used. Energy settings are standard as usually used for various sites, ranging from 20 watts at AoCusps to 40 watts in LVOT. The power, temperature and duration of RF applications may differ between patients according to the clinical needs and circumstances.

Medium-term efficacy of unipolar ablation. Medium-term efficacy of unipolar ablations is based on 24-h Holter ECG performed 1 month after ablation without any antiarrhythmic drugs (beta blockers are allowed). Efficacy is defined as \>90% reduction of PVC (from baseline Holter) and abolition of nsVT (in patients with nsVT before ablation). In patients with sVT - no sVT recurrence during one month.

Bipolar ablation. Bipolar ablation is performed in a patient with failed/unsuccessful initial unipolar ablation during with all accessible sites were mapped and EP parameters collected.

Bipolar ablation is performed using the Osypka and Carto 3 systems. The HAT500 (OSYPKA AG, Rheinfelden, Germany) generator enables to perform bipolar ablation using two ablation catheters. Power levels and impedance are recorded and displayed for both electrodes. Two open-irrigated 3.5mm or 4 mm tip mapping and ablation catheters are inserted in two adjacent locations. One ablation electrode is active and the second ablation catheter is passive (also named as return) catheter and is not visible on the electro-anatomical system screen during RF energy application.

In general, three sites for bipolar system can be used: (1) LPC, (2) GCV with its extension - AIV and (3) LVOT/AoCusps/AMC/MA. The sites for ablation electrodes positioning are chosen based on intracardiac signals (where local signals exceeds the most the onset of the QRS complex), presumed localization of intramural substrate (anatomical approach - focus should be located between the tips of active and return electrode) and safety issues (no coronary artery between the tips of electrodes based on repeated coronary angiography). Thus, the possible configurations include (1) LPC → LVOT/AoCusps/AMC/MA, (2) GCV → LVOT/AoCusps/AMC/MA or (3) LPC → GCV.

Optimal energy settings for bipolar ablation have not been yet established and are adjusted to the actual needs for effective and safe RF applications in a given patient.

Medium-term efficacy of bipolar ablation. Acute and long-term efficacy are the same as for unipolar ablation.

Coronary artery angiography. Coronary artery angiography is performed routinely during bipolar ablation and in selected patients undergoing unipolar approach (as needed). The radial or femoral artery access is used to enable repetitive contrast injections into the coronary vessels.

Assessment of quality of life. In addition, all patients will be asked to fill-in quality of life (QoL) questionnaires - before and 1 month after ablation. Two types of questionnaire will be used: the EuroQoL (EQ-5D) and the EHRA questionnaire which was developed for patients with atrial fibrillation, however, in this study it will used for patients with VA.

Eligibility criteria: Inclusion Criteria:

1. Baseline Holter ECG before initial unipolar ablation within 6 months prior to the procedure, performed without antiarrhythmic drugs (beta-blockers allowed).
2. Initial unipolar ablation of VA originating from the base of the heart (R in II, III and aVF) performed according to the standard scheme which includes detailed measurements of EP parameters at each examined and/or ablated site and inspection of all three regions (RVOT with PA, GCV and LVOT/AoCusps/AMC/MA) in cases with unsatisfactory EP parameters or failed ablation at first or second site.
3. Typical indications for ablation: a. \> 10 000 PVC in 24-hour Holter ECG or b. \> 10% PVC in 24-hour Holter ECG or c. less frequent but symptomatic PVC or d. at least 3 episodes symptomatic non-sustained ventricular tachycardia (nsVT) (\>3 QRS evolutions) in Holter ECG, regardless of the amount of PVC or e. sustained ventricular tachycardia (sVT), regardless of nsVT or PVC
4. Written informed consent

Exclusion Criteria:

1. History of \> 1 unipolar ablation for VA originating at the base of the heart
2. Lack of properly acquired EP parameters during baseline unipolar ablation
3. Lack of baseline Holter ECG performed \< 6 months prior to initial unipolar ablation
4. Absence of typical indication for ablation
5. Lack of written informed consent for participation in the study

Primary outcomes:
measure: Candidates for redo bipolar ablation
timeFrame: 2 years
Secondary outcomes:
measure: Precosity of signal predicting unipolar ablation success
timeFrame: 2 years
measure: Unipolar recording predicting unipolar ablation success
timeFrame: 2 years
measure: Pace-mapping predicting success of unipolar ablation
timeFrame: 2 years
measure: Acute efficacy of bipolar ablation
timeFrame: 2 years
measure: Mid-term efficacy of bipolar ablation
timeFrame: 2 years
measure: Precosity of signal predicting bipolar ablation success
timeFrame: 2 years
measure: Unipolar recording predicting bipolar ablation success
timeFrame: 2 years
measure: Pace-mapping predicting success of bipolar ablation
timeFrame: 2 years
measure: ECG criteria to predict origin of ventricular arrhythmia
timeFrame: 2 years
measure: Effects of ablation on QoL
timeFrame: 2 years
Other outcomes:
Locations:
city: Warsaw
country: Poland
facility: Department of Cardiology, Postgraduate Medical School, Grochowski Hospital
Study officials:
affiliation: Centre for Medical Postgraduate Education
name: Piotr Kulakowski, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre for Medical Postgraduate Education
name: Agnieszka Sikorska, MD PhD
role: STUDY_CHAIR
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