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

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.