Background
non-ischemic cardiomyopathies, Cardiovascular diseases, arrhythmia, VT/VF, fibrosis, MMVT, cardioverter defibrillators, deaths
RECURRENCES, RECURRENCE, SCAR, ARRHYTHMIA, CARDIOVASCULAR DISEASE, VENTRICULAR ARRHYTHMIA, FIBROSIS
Cardiovascular diseases account for 32% of deaths globally and 45% of deaths in Europe [While implantable cardioverter defibrillators (ICD) reduce the risk SCD due to VT/VF, they do not prevent their occurrence. Therefore, VT/VF remain major cause of morbidity and mortality as well as reduced quality of life in patients with ischemic or non-ischemic cardiomyopathies. Certain antiarrhythmic drugs (in particular amiodarone) and catheter ablation (CA) reduce the rate of VT/VF and SCD [More recently, stereotactic arrhythmia radioablation (STAR) has been introduced as a non-invasive treatment for refractory sustained MMVT with the delivery of a single fraction high-dose radiotherapy [While initial trials reported a high immediate success rate, a systematic review of the available clinical data found frequent, sustained ventricular arrhythmia (sVA) recurrences after the index procedure in up to 75% of treated patients within the first year. The commonly employed prescription dose has been 25 Gy either homogeneously or inhomogeneously to the 70–85% isodose line and was shown to maintain a high degree of safety [To date, all studies have focused on initial safety and have not yet explored a possible dose-effect relationship for developing transmural fibrosis. In human trials, to date a maximum dose of 25 Gy was prescribed to the target volume, with inhomogeneity allowed in some instances to amount to a maximum point dose of 33 Gy, which is below the anticipated threshold of 35 Gy for transmural scar formation [This study hypothesizes that the underlying mechanism of successful VT treatment is the induction of a homogeneous scar formation within the critical arrhythmic substrate for which a higher radiation dose than the currently applied 25 Gy prescription dose will be necessary. Therefore dose-escalation will lead to a significantly reduced long-term VT recurrence rate compared to the currently applied single dose of 25 Gy. This phase II study aims to identify the optimal dose - i.e. minimal efficacious dose required for successful STAR treatment, while not jeopardizing treatment safety.