ELectroanatomic substrate-guided STereotactic Ablative Radiotherapy for refractory Ventricular Tachycardia

Ventricular tachycardia (VT) is a life-threatening cardiac arrhythmia that is
associated with high mortality and morbidity rates. Antiarrhythmic drugs and
catheter-based ablation have only limited success, recurrences are frequent. A
recent development consisting of noninvasive stereotactic radiotherapy that
specifically targets the arrhythmogenic substrate has emerged to treat VT in a
small group of patients with therapy-resistant VT. In this study we evaluate
the efficacy and safety of stereotactic arrhythmia radiotherapy in patients
with refractory ventricular tachycardia using high-resolution electroanatomical
guidance.

Number of patients with >=80% reduction of VT burden, i.e., any ICD-treated or
highly-symptomatic VT episodes, at one year after STAR compared to the year
before (including VTs during the 8 week-blanking period).

Efficacy parameters will be assessed by comparing the 12 months prior to STAR
with the 12 months after treatment. All arrhythmic episodes occurring during
the blanking period will be collected.

The stereotactic ablative radiotherapy described in this protocol will be
delivered as a one-armed phase II trial to patients. Patients with structural
heart disease, a previous ICD implantation, and high burden of VTs are eligible
if 1) if the patient is ineligible to undergo invasive catheter ablation or 2)
if the VTs are persisting despite anti-arrhythmic drugs and expert catheter
ablation. Arrhythmia and safety outcomes will be assessed at 1, 3, 6, 12, and
24 months after treatment aiming to also address long-term results.

1. In preparation for stereotactic radioablation:
- Planning-CT
- ECG-imaging.
- SF-36 and EQ5D questionnaires.

2. Stereotactic radioablation with single-fraction ablative dose of radiation.

3. Follow-up STAR (up to 2 years):
- ECG-imaging.
- Cardiac CT.
- (Non) invasive programmed ventricular stimulation and STAR-targeted
arrhythmia substrate characterization during invasive electroanatomical
evaluation.
- 2D/3D MRI cor (optional).
- SF-36 and EQ5D questionnaires.

Study subjects will undergo additional investigations prior to STAR which
impose risks:
- Planning CT (including cardiac CT for ECG-imaging): minor risk of allergic
reaction to contrast agent or skin electrodes, contrast nephropathy.
Anticipated 6-20 mSV.

STAR with a single 25 Gy will last 60 minutes. It is not painful. The
intermediate and longterm risks maybe ICD or lead damage, reduction of LVEF,
pericardial effusion, long inflammation or coronary damage.

Six months post-STAR a electrostructural evaluation of the radiated area will
be performed:
- CT (for pulmonary damage and ECG-imaging): minor risk of allergic reaction to
contrast agent or skin electrodes, contrast nephropathy. Anticipated6-20 mSV.
- Cardiac MR: claustrophobia, ICD malfunction, ICD lead heating, allergic
reaction to gadolinium.
- Elimination and modification of the STAR-targeted arrhythmia substrate as by
noninducibility of sustained VT, scar voltage reduction and -inexcitability
during electroanatomical mapping: minor risk of CVA, pericardial effusion,
untreatable VT/VF (also during noninvasive programmed electrical stimulation),
or, in extreme cases, death.

Benefit:
We anticipate a strong individual benefit of STAR in terms of reduction of VT
burden and ICD interventions.