Stereotactic Radioablation as First-Line Therapy for Scar-Related Ventricular Tachycardia (START-VT)

Stereotactic Arrhythmia Radioablation as First-Line Treatment for Scar-Related Ventricular Tachycardia

Ventricular tachycardia (VT) is a dangerous fast heart rhythm originating from scarred areas of the heart muscle, often after a heart attack or in patients with cardiomyopathy. Patients with VT and structural heart disease typically receive an implantable cardioverter-defibrillator (ICD) to prevent sudden death. Despite the ICD, recurrent VT and ICD shocks remain common and are associated with poor quality of life. Current preventive therapies - antiarrhythmic medications and catheter radiofrequency ablation - have important limitations including side effects, incomplete effectiveness, and procedural risk.

Stereotactic Arrhythmia Radioablation (STAR) is a non-invasive treatment in which a single, precisely targeted dose of radiation is delivered to the scar tissue that gives rise to the abnormal heart rhythm. STAR has previously been studied in patients who have failed catheter ablation or are too high risk for that procedure, with promising results. However, STAR has not been formally evaluated as a first-line treatment.

This single-arm prospective feasibility study will enroll 20 adults with structural heart disease and sustained monomorphic VT. Each participant will receive a single 25 Gy fraction of stereotactic body radiotherapy (VMAT technique) targeted at the arrhythmogenic substrate identified by cardiac imaging, 12-lead ECG, and (where available) non-invasive electrocardiographic mapping or electroanatomical mapping. Participants will be followed at 6 weeks, 3, 6, 9, and 12 months to assess the primary efficacy outcomes (death, appropriate ICD shock, VT storm, and sustained VT below ICD detection rate after a 6-week blanking period) and safety outcomes (acute heart failure decompensation, drop in left ventricular ejection fraction, and STAR-specific toxicities such as pneumonitis, esophagitis, and pericarditis). The hypothesis is that STAR delivered as first-line therapy is safe and effective, with a comparable toxicity and efficacy profile to catheter radiofrequency ablation.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiomyopathies; Ventricular Tachycardia, Monomorphic
• Intervention / Treatment: Radiation: Stereotactic Arrhythmia Radioablation

Detailed Description

Background:

Approximately 50,000 Canadians die suddenly each year. Ventricular tachycardia (VT) is the most common cause of sudden cardiac death, with the most common substrate being scar from prior myocardial infarction or non-ischemic cardiomyopathy. Implantable cardioverter-defibrillators (ICDs) reduce mortality but do not prevent recurrent VT; ICD shocks are painful, impair quality of life, and are independently associated with hospitalization and death.

Current strategies to prevent VT - antiarrhythmic drugs (primarily amiodarone) and catheter radiofrequency ablation (RFA) - both have significant limitations. Amiodarone use is limited by recurrence and adverse effects in up to 30% of patients. RFA is more effective than drug escalation but is limited by inability to access deep intramural, sub-epicardial, or papillary muscle substrate, hemodynamic instability during ablation, and large scar burden. Despite RFA, 20-50% of patients experience VT recurrence, with higher rates in non-ischemic etiology.

Stereotactic Arrhythmia Radioablation (STAR) - also called cardiac SBRT or cardiac radioablation - uses high-dose photon radiotherapy precisely delivered to the arrhythmogenic substrate. STAR is non-invasive and can target three-dimensional volumes anywhere in the heart, overcoming many of the access limitations of catheter-based ablation. Initial trials in patients ineligible for or refractory to catheter ablation have demonstrated safety and significant reductions in arrhythmia burden. A 2024 systematic review and meta-analysis of prospective trials (Miszczyk et al., Heart Rhythm 2024) reported VT burden reductions of >50%, >75%, and >95% in 90%, 80%, and 61% of evaluable patients respectively, with adverse events in fewer than 10%.

Southlake Regional Health Centre has previously completed an REB-approved feasibility study in 6 patients with refractory VT (acceptable toxicity, excellent outcome) and has subsequently treated 14 additional patients with recurrent VT despite prior catheter ablation under grant-supported studies. Earlier referral to ablation is associated with improved patient outcomes (Romero et al., JACC Clin Electrophysiol 2018), motivating a formal evaluation of STAR as a first-line treatment.

Hypothesis:

STAR is a safe and effective first-line treatment for patients with VT secondary to structural heart disease, with a comparable toxicity and efficacy profile to standard catheter radiofrequency ablation.

Objectives:

1. To evaluate the efficacy of STAR as first-line treatment for patients with VT secondary to structural heart disease.
2. To assess the safety profile of STAR with respect to acute (<6 weeks) and late (>6 weeks) complications.

Study Design:

This is a single-arm prospective feasibility / workflow-implementation study. 20 adult patients will be enrolled at Southlake Regional Health Centre.

Intervention:

Following eligibility assessment and informed consent, each participant will undergo:

• A specialized cardiac CT to characterize the location and extent of myocardial scar.
• (Where appropriate) arrhythmia induction using the patient's own ICD to obtain a 12-lead VT morphology, and/or non-invasive ECGI mapping with a 252-electrode vest, and/or 3-D electroanatomical mapping when prior catheter ablation has been performed.
• 4D-CT simulation for radiotherapy planning, with delineation of organs at risk (lung, esophagus, stomach, spinal cord, coronary vessels).
• A single 25 Gy fraction of VMAT-based stereotactic body radiotherapy delivered to the clinical target volume (arrhythmogenic scar). In selected cases with large planning target volumes or proximity to critical organs at risk, treatment may be delivered in 2 fractions 24-48 hours apart.

Follow-up:

Participants are followed at 6 weeks, 3, 6, 9, and 12 months in the Heart Rhythm Device Clinic and Radiation Oncology clinic. ICDs are interrogated at every device-clinic visit. 2-D echocardiograms are obtained at 3 months. Chest x-rays are obtained at 1 and 6 months, and CT scans at 3 and 12 months.

A 6-week blanking period follows STAR. During this window antiarrhythmic therapy may be increased; thereafter it may be reduced or stopped to assess the effect of STAR.

Data and Safety Monitoring:

An independent Data Safety and Monitoring Board (DSMB) comprising an electrophysiologist, a cardiologist, and a radiation oncologist will review safety data on an ongoing basis and may recommend study termination. Adverse events are graded by CTCAE v5. The pre-specified safety threshold is a ≤20% rate of serious adverse events.

Outcomes:

Primary efficacy outcomes (post 6-week blanking period): death, appropriate ICD shock, VT storm (>3 episodes in 24 hours), and sustained VT below ICD detection rate.

Secondary efficacy outcomes: ICD shocks at any time, VT storm at any time, sustained VT below ICD detection at any time, overall VT burden, hospital admission for cardiac causes, hospital admission for radiation-related complications, and quality-of-life change.

Primary safety outcomes (3 months acute / 6 months late): acute heart failure decompensation requiring new IV inotropes/vasopressors, acute LVEF reduction >10%, and any STAR-specific toxicity including pneumonitis, esophagitis, and pericarditis.

Analysis:

Descriptive statistics; chi-square for categorical variables, t-test or Mann-Whitney U for continuous variables comparing patients with long-term procedural success vs. failure. SPSS v26.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Mouhannad Sadek, MD; Phone Number: 905-895-4521; Email: msadek@southlake.ca

Study Locations

• Canada
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18 years or older and able to provide informed consent
• Structural heart disease with myocardial fibrosis identified on pre-procedural imaging, including imaging evidence of regional myocardial akinesis/thinning or documented scar on echocardiography, cardiac CT, or cardiac MRI
• Sustained monomorphic ventricular tachycardia (symptomatic or requiring ICD shocks for termination) within the previous 6 months

Exclusion Criteria:

• Reversible causes of VT (e.g., active ischemia, drug-induced, electrolyte abnormalities)
• Acute coronary syndrome within 30 days, coronary revascularization (<90 days for bypass surgery, <30 days for percutaneous coronary intervention)
• Patients previously treated with high-dose radiotherapy that precludes safe delivery of thoracic stereotactic radiotherapy (relative contraindication)
• Patients requiring chest radiotherapy for an active cancer (relative contraindication)
• VT targets cannot be identified or are not suitable for targeting with stereotactic radiotherapy (such as multiple foci of arrhythmia)
• Patients who cannot tolerate the radiotherapy treatment position, or whose body habitus is not permissible by treatment bed requirements
• Pregnant or breast-feeding women
• Patients being considered for cardiac transplant who are deemed not eligible by their transplant team for STAR

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: STAR (Stereotactic Arrhythmia Radioablation); Single 25 Gy fraction of VMAT-based stereotactic body radiotherapy delivered to the arrhythmogenic substrate identified by cardiac CT, 12-lead ECG of the clinical arrhythmia, and (where available) non-invasive electrocardiographic mapping or electroanatomical mapping. In selected cases with large planning target volumes or proximity to organs at risk, the dose may be delivered in 2 fractions 24-48 hours apart. Participants are followed for 12 months for arrhythmia outcomes and radiation toxicity.

Radiation: Stereotactic Arrhythmia Radioablation; Single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered using a volumetric modulated arc therapy (VMAT) technique with 6 MV FFF photons on an Elekta Agility linear accelerator. The clinical target volume (arrhythmogenic scar) is delineated by the radiation oncologist and electrophysiologist using cardiac CT, 12-lead ECGs of the clinical arrhythmia, and (where available) non-invasive electrocardiographic mapping (252-electrode CardioInsight vest) and/or 3-D electroanatomical mapping. A 4D-CT simulation accounts for cardiac and respiratory motion. In selected cases with a large planning target volume or proximity to critical organs at risk (stomach, esophagus, spinal cord), the dose may be delivered in 2 fractions 24-48 hours apart. Treatment is delivered with image guidance (cone-beam CT) on the day of treatment. Total dose: 25 Gy in 1 or 2 fractions.; Other Names: Cardiac SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of death, appropriate ICD shock, VT storm, or sustained VT below ICD detection (after 6-week blanking period)	Proportion of participants experiencing at least one of the following events after the 6-week post-treatment blanking period: (1) death from any cause; (2) appropriate ICD shock; (3) VT storm, defined as >3 episodes of VT within 24 hours; or (4) sustained VT below the ICD detection rate requiring external cardioversion, pharmacologic conversion, or manual ICD cardioversion (shock or ATP). ICDs will be interrogated at every device-clinic visit.	From 6 weeks post-treatment through 12 months follow-up
Safety: Composite of serious adverse events related to STAR	Proportion of participants experiencing any of the following: (1) acute worsening of heart failure requiring initiation of new IV vasoactive medications (inotropes or vasopressors) within the first 6 weeks; (2) acute reduction in left ventricular ejection fraction greater than 10 percentage points within the first 6 weeks; (3) any STAR-specific symptom including esophagitis, pneumonitis, or pericarditis assessed by CTCAE v5. The pre-specified safety threshold is a serious adverse event rate of <=20%.	Acute (<6 weeks post-treatment) and late (up to 6 months post-treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ventricular tachycardia burden	Change from baseline in the number of treated and monitored VT episodes, based on ICD device interrogation at each follow-up visit (6 weeks, 3, 6, 9, and 12 months) compared to the 6 months prior to STAR treatment.	Baseline (6 months prior to treatment) through 12 months post-treatment
Hospital admissions for cardiac or radiation-related causes	Number of hospital admissions for cardiac causes and number of hospital admissions for radiation-related complications, recorded at each follow-up visit (6 weeks, 3, 6, 9, and 12 months).	From treatment through 12 months follow-up

Collaborators and Investigators

• Sponsor: Southlake Health

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: May 24, 2026
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Radioablation; Stereotactic Body Radiotherapy; Implantable Cardioverter Defibrillator; Cardiac Radioablation; STAR-VT
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Tachycardia; Pathological Conditions, Signs and Symptoms; Cardiomyopathies; Tachycardia, Ventricular
• Other Study ID Numbers: S-041-2425

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