Non-invasive Ablation of Ventricular Tachycardia

Study Overview
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Brief Summary
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Phase I/II study of 4-D Navigated Non-invasive radiosurgical ablation of ventricular tachycardia (NIRA-VT).

Detailed Description
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The goal of this project dealing with 4D-navigated substrate ablation is to evaluate the feasibility and safety of elimination of the scar-related monomorphic ventricular tachycardia (VT) or tachycardias by stereotactic radiosurgical ablation that is completely non-invasive. The arrhythmic substrate is defined as the scar after myocardial infarction (MI) described by transthoracic echocardiography (TTE) and specified by PET-CT or MRI. All sustained monomorphic VT induced by programmed ventricular stimulation via implanted ICD (Implantable Cardioverter Defibrillator) will be analyzed using body surface ECG mapping. The target volume for stereotactic radiosurgical ablation (single dose of 25 Gy) will be based on accordance between a post-infarction scar (PET-CT or MRI imaging) and arrhythmic substrate (body surface ECG mapping).

Official Title
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Phase I/II Study of 4-D Navigated Non-invasive Radiosurgical Ablation of Ventricular Tachycardia

Conditions
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Ventricular Tachycardia

Intervention / Treatment
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* Procedure: 4-D navigated stereotactic radiosurgical ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: history of sustained monomorphic VT or termination of monomorphic VT by ICD (appropriate therapy) during previous 6 months prior to enrollment implantation ICD inducibility at least one of monomorphic ventricular tachycardia by ICD during EP study with programmed ventricular stimulation history of myocardial infarction (MI) left ventricular scar and decreased systolic function of the left ventricle (ejection fraction of left ventricle less than 40%) based on transthoracic ultrasound stable chronic heart failure (NYHA II-III) older than 18 years signed an IRB approved written informed consent document. failed at least one invasive catheter ablation procedure or have a contraindication to a catheter ablation procedure Exclusion Criteria: acute myocardial infarction chronic heart failure NYHA IV channelopathy reversible cause of VT (e.g. ionic dysbalance, intoxications) pregnancy or breastfeeding history of chest radiotherapy arrhythmic substrate larger than 100 ccm

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: All patients enroled in the study are allocated to one group with 4-D navigated stereotactic radiosurgical ablation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4-D navigated stereotactic radiosurgical ablation<br>The patients enroled to this arm of the study will undergo 4-D navigated stereotactic radiosurgical ablation. | Procedure: 4-D navigated stereotactic radiosurgical ablation<br>* 4-D Navigated Non-invasive radiosurgical ablation of ventricular tachycardia in patients with sustained monomorphic ventricular tachycardia/tachycardias after myocardial infarction.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of death | Composite of death occurring at any time after treatment or arrhythmic storm (three or more documented episodes of VT within 24 hours) or appropriate ICD therapy (both shock and pacing) after a 90-day treatment period. 90-day treatment period was imposed to exclude nonfatal outcomes that might occur during acute radiation reaction. Moreover, functional radiosurgery has 90% success rate after 3 months. | 90 days | 
| Acute radiation-induced events | Acute radiation-induced events (within 3 months after treatment) according to CTCAE 4.0. Major concern will be on radiation myocarditis, pericarditis and pneumonitis/fibrosis. Needs of antiemetic drugs will be recorded. | 18 months | 
| Late radiation-induced effects | Late radiation-induced effects (after 3 months after treatment) according to CTCAE 4.0. Major concern will be on radiation myocarditis, pericarditis and pneumonitis/fibrosis. Needs of antiemetic drugs will be recorded. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to death at any time |  | 18 months | 
| Time to arrhythmic storm | Time to arrhythmic storm (three or more documented episodes of VT within 24 hours) at any time and after 90-day treatment period. | 90 days | 
| Time to appropriate ICD shock | Time to appropriate ICD shock at any time and after 90-day treatment period. | 90 days | 
| Time to appropriate antitachycardial pacing by ICD | Time to appropriate antitachycardial pacing by ICD at any time and after 90-day treatment period. | 90 days | 
| Hospitalization due to VT |  | 18 months | 
| Hospitalization due to chronic heart failure |  | 18 months | 
| Quality of life measured with EQ-5D questionnaire | Quality of life measurement using a standardised tool named EQ-5D. EQ-5D is a standardised instrument in the form of a questionnaire developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The EQ-5D instrument consists of a descriptive system and the EuroQol-visual analogue scales (EQ VAS). The quality of life is measured in 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The higher the score achieved, the higher the quality of life of the patient. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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scar-related, ventricular tachycardia, substrate ablation, stereotactic radiosurgery, functional radiosurgery, 4D navigation