Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia

Patients with Ventricular Tachycardia (VT) who have failed standard therapy (medicines, invasive catheter ablation) have limited options, with one-year survival below 20%. Preclinical data demonstrate that single fraction stereotactic body radiotherapy (SBRT) to discrete portions of the heart is feasible and may result in a reduction or elimination of VT. The efficacy may be further improved when guided by cardiac electrophysiologic (EP) testing. In total, the mapping and ablation proposed for this EP-guided Noninvasive Cardiac Radioablation (ENCORE) is a rapid and totally non-invasive method. Overall safety and early efficacy of ENCORE have not been rigorously studied in a prospective trial to-date. The purpose of this phase I/II study is to demonstrate the short-term safety and preliminary efficacy of ENCORE for patients with life-threatening, treatment-refractory VT.

Inclusion criteria

• DOCUMENTED VT:

• Patient must have documented sustained monomorphic ventricular tachycardia as documented on either a 12-lead ECG or intracardiac ICD interrogation

• OR-
• Monomorphic PVCs documented on a 12-lead ECG.
• ANTIARRHYTHMIC MEDICATION: Patient must have failed or become intolerant to at least one antiarrhythmic medication (amiodarone, sotalol, or mexiletine).

-AND-

• CATHETER ABLATION: Patient must have failed at least one invasive catheter ablation procedure, or have a contraindication to a catheter ablation procedure (e.g., LV thrombus, severe pulmonary disease), or have VT thought to arise from a protected location (e.g., epicardial VT with history of previous cardiac surgery).
• MINIMUM VT BURDEN: Patient must have either:

• At least 3 VT episodes (sustained VT, ICD ATP or ICD shock) over previous 6 months prior to enrollment -OR-
• >20% PVC burden with a cardiomyopathy (LVEF<50%)
• Patient must be deemed medically fit for stereotactic body radiation therapy by the treating physician.
• Patient must be > 18 years old.
• Patient must be able to understand and be willing to sign an IRB approved written informed consent document.

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Exclusion criteria

• Patient must not have past history of radiotherapy within the projected treatment field.
• Advanced symptomatic heart failure as defined as NYHA Class IV heart failure (inotrope dependent and/or current left-ventricular assist device (LVAD))
• Polymorphic VT or ventricular fibrillation (VF) as a clinical heart rhythm (as determined by 12-lead ECG and/or ICD interrogation).
• More than 3 distinct clinical VT morphologies observed (ECG or ICD interrogation or invasive EP study) OR more than 5 distinct induced VT morphologies during ECGI testing.
• Advanced myocardial scar substrate that would require stereotactic delivery to a target volume deemed unsafe by the treating physician.
• Unlikely to live 12 months, in the absence of VT, as best based on clinical judgment by the treating and enrolling physicians.
• Patient must not be pregnant and/or breastfeeding and must have a negative pregnancy test within 14 days of study entry.

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