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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Functional substrate mapping only without VT induction | Experimental | 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. |
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| Standard VT Mapping | Active Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Functional Substrate-Only Mapping without VT Induction | 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. |
| 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 |
| 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 Mapping Time |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gordon Ho, MD | VA San Diego Healthcare System, San Diego, CA | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA San Diego Healthcare System, San Diego, CA | San Diego | California | 92161-0002 | United States |
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| ID | Term |
|---|---|
| D017180 | Tachycardia, Ventricular |
| D016757 | Death, Sudden, Cardiac |
| ID | Term |
|---|---|
| D013610 | Tachycardia |
| D001145 | Arrhythmias, Cardiac |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D014965 | X-Rays |
| ID | Term |
|---|---|
| D060733 | Electromagnetic Radiation |
| D055590 | Electromagnetic Phenomena |
| D060328 | Magnetic Phenomena |
| D055585 | Physical Phenomena |
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Randomized controlled trial
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This is a prospective, single-blinded, randomized controlled trial comparing an experimental strategy of functional substrate mapping/ablation only without VT induction compared to standard VT mapping/ablation. The study subjects will be blinded to the randomization. The care providers doing the procedure (and/or investigators doing the procedure) cannot be blinded by nature of the intervention (either perform experimental mapping protocol or not).
|
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| Standard-of-Care Mapping/Imaging | 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. |
|
dwell time of multi-electrode mapping catheters |
| 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 |
| 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 |
| 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 |
| D000075224 |
| Cardiac Conduction System Disease |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006323 | Heart Arrest |
| D003645 | Death, Sudden |
| D003643 | Death |
| D011827 | Radiation |
| D011839 | Radiation, Ionizing |