Noninvasive Cardiac Radioablation for Ventricular Tachycardia Refractory to Medication and Catheter Ablation
Noninvasive Cardiac Radioablation for Ventricular Tachycardia Refractory to Medication and Catheter Ablation
The purpose of this study is to evaluate the safety and efficacy of cardiac radioablation
 (CRA) as a means of noninvasive treatment of ventricular tachycardia (VT) refractory to both
 medication and catheter ablation.
Ventricular tachycardia (VT) is a regular, rapid (faster than 100 beats per minute) abnormal
 heart rhythm resulting from aberrant electrical conduction in the ventricles of the heart.
 Coronary heart disease is responsible for the majority of VT cases. Defibrillation and
 antitachycardia pacing, effective means of terminating a life-threatening acute episode of
 VT, can be delivered via implantable cardioverter-defibrillator (ICD). ICDs are able to both
 monitor the heart rhythm continuously and deliver therapy in response to tachycardia that
 meets pre-programmed detection criteria. For patients with VT refractory to medical
 management requiring multiple ICD shocks, electrophysiologic mapping may be utilized to
 localize the arrhythmogenic focus, which can be subsequently ablated with cardiac catheter
 radiofrequency ablation. The goal of catheter ablation is to identify (through
 electroanatomical mapping) and then eliminate the channels of surviving myocardium within the
 substrate. Many patients experience continued episodes of VT refractory to both medication
 and multiple catheter ablation attempts. ICD shocks are associated with substantially
 increased risk of hospitalization, quality of life impairment, and death.

 Stereotactic body radiotherapy (SBRT) is a technique used most commonly as a cancer
 treatment, whereby a precise, high dose of radiation is delivered to a target. For patients
 with VT refractory to medication and catheter ablation, noninvasive targeting of the
 arrhythmogenic substrate with SBRT (in this case termed cardiac radioablation, CRA) is an
 emerging technique demonstrating favorable efficacy.

 Using a protocol similar to that utilized by the phase I/II ENCORE-VT trial (NCT02919618),
 this study aims to replicate previously reported favorable results in a multi-institutional
 setting. Accrued patients will receive CRA to 25 Gy in a single fraction.
Inclusion Criteria:

 -  Patients must be ≥ 18 years old.

 -  Patients must have documented sustained monomorphic VT by 12-lead ECG or intracardiac
 ICD interrogation.

 -  Minimum VT burden: 4 or more documented VT episodes (including sustained VT, ICD
 anti-tachycardia pacing [ATP], or ICD shock) in the 5 months preceding enrollment
 on this trial. Patients must have at least two episodes of
 electrocardiographically documented symptomatic, recurrent, sustained monomorphic
 VT in the 3 months prior to enrollment

 -  *ATP and appropriate ICD shock are acceptable surrogates for VT-associated
 symptoms

 -  Patients must have an ICD.

 -  Patients must have ischemic or non-ischemic cardiomyopathy previously diagnosed with
 LVEF ≤ 35%.

 -  Patients must have received at least one antiarrhythmic medication (i.e. amiodarone,
 sotalol, mexiletine) without control of symptoms or with poor toleration. AND Patients
 must have undergone at least one catheter-ablation procedure (or have a
 contraindication to catheter-ablation) or have VT arising from an inaccessible
 location.

 -  Contra-indications to endocardial catheter ablation procedure include dual aortic
 and mitral mechanical valves, active left ventricular thrombus, and anesthesia
 intolerance.

 -  Contra-indications to epicardial catheter ablation include prior cardiac surgery
 or anesthesia intolerance.

 -  Patients with ischemic cardiomyopathy should have failed at least one endocardial
 ablation performed at an academic center.

 -  Patients with non-ischemic cardiomyopathy should have failed both epicardial and
 endocardial ablations, unless epicardial mapping/ablation is not feasible.

 -  Ability to understand and willingness to sign an IRB approved informed consent
 document (legally authorized representatives are not permissible).

 -  An independent EP cardiologist must confirm that each study participant has met the
 study entrance criteria, has failed conventional therapies, and has frequent recurrent
 VT episodes that warrant further rhythm management.

 Exclusion Criteria:

 -  Patients who have received any prior radiotherapy to the internal organs of the thorax
 or upper abdomen (with treatment field extending superior to L1 vertebral body) at any
 time in the past are excluded.

 -  Patients found to have multiple scars on electrocardiographic imaging where the source
 of reentrant focus is unclear despite positron emission tomography (PET)/magnetic
 resonance imaging (MRI) are excluded.

 -  Patients who have congestive heart failure on inotropes (NYHA class 4B) or
 left-ventricular assist device are excluded.

 -  Patients felt to be unlikely to live 12 months in the absence of VT are excluded.

 -  Patients with polymorphic VT or ventricular fibrillation, >3 distinct clinical VT
 morphologies on ICD interrogation, or >5 induced VT morphologies during noninvasive
 testing are excluded.

 -  Patients with multiple, spatially separate target substrates (targets with presumed
 inclusion of nonadjacent ventricular segments) deemed unsafe to treat with CRA by the
 treating physician will be excluded.

 -  Patients with incessant VT that is hemodynamically unstable are excluded.

 -  Patients in VT storm are excluded.

 -  Patients must not be pregnant and must have a negative pregnancy test within 14 days
 of study entry if they are females of childbearing age.