Functional Substrate-Only Guided VT Ablation (SLO-VT)

Functional Substrate-Only Mapping Technique to Guide Ablation of Arrhythmogenic Substrate Underlying Ventricular Tachycardia

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Ventricular Tachycardia; Sudden Cardiac Death
• Intervention / Treatment: Procedure: Functional Substrate-Only Mapping without VT Induction; Procedure: Standard-of-Care Mapping/Imaging

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

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92161-0002
      • VA San Diego Healthcare System, San Diego, CA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Procedure: 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.; Other Names: Isochronal late activation mapping (ILAM), peak frequency analysis
Active Comparator: 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.	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to composite endpoint (VT recurrence, death, or acute hemodynamic decompensation)	Ventricular arrhythmia recurrence is defined by an episode of sustained VT lasting 30 seconds or appropriate implantable cardioverter-defibrillator therapy including anti-tachycardia pacing or shock. Acute hemodynamic decompensation is defined by escalation of at least 1 new high dose inotrope/pressor occurring after anesthesia induction with persistent requirement during stable rhythm, >20% drop in cardiac index, unplanned insertion of percutaneous hemodynamic support device.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VT burden (ICD therapy including shocks and ATP, sustained VT episodes >30 seconds)	Total number of ICD therapies (ATP and shocks) and recorded sustained VT episodes>30 seconds, compared 6 months before and 6 months after ablation.	6 months
total procedural time	time from introduction of catheters to removal of catheters	immediately at the end of the procedure
Procedural adverse events or complications	Major complications include: new acute pericardial effusion requiring intervention, vascular complication requiring intervention, embolic stroke confirmed by brain imaging, limb ischemia requiring intervention, or bacteremia. Major adverse events include: cardiogenic shock (requiring escalation of inotropes or salvage mechanical circulatory support)	1 month
Total fluoroscopy time	Total amount of fluoroscopy time during the entire procedure	immediately at the end of the procedure
Total Mapping Time	dwell time of multi-electrode mapping catheters	immediately at the end of the procedure
Use of general anesthesia	Whether general anesthesia (intubation) is required/used during the procedure	immediately at the end of the procedure
Acute heart failure readmission	unexpected readmission after index ablation discharge	1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
total procedural time	time from introduction of catheters to removal of catheters	immediately at the end of the procedure
Procedural adverse events or complications	Major complications include: new acute pericardial effusion requiring intervention, vascular complication requiring intervention, embolic stroke confirmed by brain imaging, limb ischemia requiring intervention, or bacteremia. Major adverse events include: cardiogenic shock (requiring escalation of inotropes or salvage mechanical circulatory support)	1 month
Number of vascular access sites	Total number of sheaths inserted into the femoral veins and arteries	immediately at the end of the procedure
Total fluoroscopy time	Total amount of fluoroscopy time during the entire procedure	immediately at the end of the procedure

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Gordon Ho, MD, VA San Diego Healthcare System, San Diego, CA

Publications and helpful links

General Publications

• Krummen DE, Villongco CT, Ho G, Schricker AA, Field ME, Sung K, Kacena KA, Martinson MS, Hoffmayer KS, Hsu JC, Raissi F, Feld GK, McCulloch AD, Han FT. Forward-Solution Noninvasive Computational Arrhythmia Mapping: The VMAP Study. Circ Arrhythm Electrophysiol. 2022 Sep;15(9):e010857. doi: 10.1161/CIRCEP.122.010857. Epub 2022 Sep 7.
• Fox SR, Toomu A, Gu K, Kang J, Sung K, Han FT, Hoffmayer KS, Hsu JC, Raissi F, Feld GK, McCulloch AD, Ho G, Krummen DE. Impact of artificial intelligence arrhythmia mapping on time to first ablation, procedure duration, and fluoroscopy use. J Cardiovasc Electrophysiol. 2024 May;35(5):916-928. doi: 10.1111/jce.16237. Epub 2024 Mar 4.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2026
• Primary Completion (Estimated): September 28, 2029
• Study Completion (Estimated): April 1, 2030

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: June 14, 2024
• First Posted (Actual): June 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: functional substrate mapping; conduction slowing; isochronal late activation mapping (ILAM); peak frequency signal analysis; deceleration zones
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Death; Heart Arrest; Death, Sudden; Tachycardia; Pathological Conditions, Signs and Symptoms; Death, Sudden, Cardiac; Tachycardia, Ventricular; Physical Phenomena; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; X-Rays
• Other Study ID Numbers: CARA-007-23F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No