Functional Substrate-Only Guided VT Ablation

NCT ID: NCT06464315

Last Updated: 2025-11-06

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-17
• Study Completion Date: 2030-04-01

Brief Summary

Ventricular tachycardia (VT) is a leading cause of death and suffering in the Veteran population. Currently, ablation procedures are performed to destroy the diseased tissue that causes this problem. This study will test to see if an experimental strategy of only targeting regions of slow conduction without the induction of VT can improve the efficacy and safety of VT ablation. Once this study is completed, the investigators will know whether this ablation strategy could help increase the efficacy, safety and efficiency of ablation therapy of fatal heart rhythms.

Detailed Description

Ventricular tachycardia (VT) remains a leading cause of death and morbidity in the veteran population, but current ablation procedures to treat VT are limited by hemodynamic instability of induced VT during standard invasive activation mapping (up to 80% of induced VT), lengthy ablation procedures (~8 hours), and difficulty in accurately localizing the critical origination sites of VT. The long-term goal is to simplify VT ablation using invasive functional substrate mapping techniques to improve the safety, efficacy, and efficiency of VT catheter ablation. The overall objectives in this application are to i) perform a randomized clinical trial to test whether performing simplified VT ablation guided only by invasive functional substrate mapping without VT induction improves the safety and efficiency of VT ablation while maintaining similar efficacy compared to standard ablation and ii) mechanistically correlate abnormal functional substrate with VT origination sites localized using gold standard invasive activation mapping. The central hypothesis is that ablation of slowly conducting tissue characterized by high frequency signals is sufficient to eliminate VT and improves clinical outcomes of VT ablation. The rationale is that recently developed sophisticated techniques to characterize functionally abnormal tissue can localize critical VT-sustaining substrate without needing to subjecting patients to mapping of hemodynamically unstable VT which is routinely done during standard of care ablation. The central hypothesis will be tested by pursuing one primary specific aim: Perform a randomized clinical trial to determine whether VT ablation guided only by invasive functional substrate mapping without VT induction decreases procedure time, fluoroscopy time, and procedural complications while maintaining similar efficacy compared to standard VT ablation controls. This study also includes 2 sub-aims to uncover VT mechanisms characterizing the distance of slowly conducting tissue to VT exit sites and provide a method to unmask critical arrhythmogenic substrate in non-ischemic cardiomyopathy patients in whom scar is not easily identified. The research proposed is innovative because it tests a novel strategy using new algorithms that can identify the critical tissue sustaining VT without requiring the induction of VT. The proposed research is significant because a functional substrate-guided only approach to VT ablation while still localizing the critical tissue causing VT is expected to increase the safety, efficacy, and efficiency of treating a fatal heart rhythm disorder

Conditions

Ventricular Tachycardia; Sudden Cardiac Death

Keywords

functional substrate mapping; conduction slowing; isochronal late activation mapping (ILAM); peak frequency signal analysis; deceleration zones

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Functional substrate mapping only without VT induction

In this experimental arm, only functional substrate mapping will be used to guide ablation of conduction slowing regions, without VT induction or mapping during VT. Ablation targets of conduction slowing will be identified as: 1) deceleration zones of conduction slowing, previously defined as 3 isochrones coalescing within 1cm radius. 2) wavefront discontinuities represented by lines of conduction block, previously defined as late potentials with at least 20ms of isoelectric segment, and 3) regions of slow conduction characterized by high peak frequency (220-500Hz), which uses spectral frequency analysis to identify signals with highest frequency as a surrogate for slow conduction. All regions exhibiting any of these 3 surrogates of slow conduction will be ablated.

Group Type: EXPERIMENTAL

Functional Substrate-Only Mapping without VT Induction

Intervention Type: PROCEDURE

In this arm, invasive maps will be constructed by annotating the latest deflection and peak frequency during voltage mapping of stable intrinsic rhythm to localize areas of slow conduction. Annotated algorithms are cleared by the FDA. No VT will be purposefully induced in this experimental arm.

Standard VT Mapping

Standard-of-care mapping, including voltage mapping of intrinsic rhythm, entrainment, activation, and/or pace mapping, will be performed to guide VT ablation. Standard VT induction protocols will be performed.

Group Type: ACTIVE_COMPARATOR

Standard-of-Care Mapping/Imaging

Intervention Type: PROCEDURE

Conventional invasive scar (voltage) and electrical VT (entrainment, activation, pace) mapping will be used to guide VT ablation. Functional substrate mapping will not be used in this arm. VT will be induced using standard protocols.

Interventions

Functional Substrate-Only Mapping without VT Induction

In this arm, invasive maps will be constructed by annotating the latest deflection and peak frequency during voltage mapping of stable intrinsic rhythm to localize areas of slow conduction. Annotated algorithms are cleared by the FDA. No VT will be purposefully induced in this experimental arm.

Intervention Type: PROCEDURE

Standard-of-Care Mapping/Imaging

Conventional invasive scar (voltage) and electrical VT (entrainment, activation, pace) mapping will be used to guide VT ablation. Functional substrate mapping will not be used in this arm. VT will be induced using standard protocols.

Intervention Type: PROCEDURE

Other Intervention Names

Isochronal late activation mapping (ILAM), peak frequency analysis

Eligibility Criteria

Inclusion Criteria

• Men and women >18 years of age referred for clinically indicated VT ablation and experience monomorphic or polymorphic scar-based VT documented by telemetry, ICD interrogation, ECG or event monitoring.
• Scar-based VT is defined as VT in patients with structural heart disease (assessed with either abnormal nuclear perfusion imaging (>5% defect), late gadolinium uptake on cardiac MRI, wall thinning <10mm or calcified myocardium on cardiac CT, akinesis or hypokinesis on echocardiogram, presence of Q waves on ECG, history of myocardial infarct).
• Patients undergoing epicardial VT ablation and who undergo prophylactic percutaneous hemodynamic support devices will also be included.

Exclusion Criteria

• Patients without structural heart disease will be excluded from the pri-mary analysis, but enrolled in a prospective registry
• Patients who are pregnant
• Presence of intracardiac thrombus
• active acute coronary ischemia with unrevascularized coronary artery disease (CAD >70% stenosis)
• Active bacteremia
• Inaccessible ventricles due to dual mechanical valves
• Inability to tolerate and inability to tolerate anticoagulation during ablation and for at least 1 month after ablation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gordon Ho, MD

Role: PRINCIPAL_INVESTIGATOR

VA San Diego Healthcare System, San Diego, CA

Locations

VA San Diego Healthcare System, San Diego, CA

San Diego, California, United States

Countries

United States

Central Contacts

Gordon Ho, MD

Role: CONTACT

Phone: (858) 642-3147

Email: Gordon.Ho@va.gov

Nicholas W Wettersten, MD

Role: CONTACT

Phone: (858) 642-3048

Email: Nicholas.Wettersten@va.gov

Facility Contacts

Gordon Ho, MD

Role: primary

Other Identifiers

CARA-007-23F

Identifier Type: -

Identifier Source: org_study_id