Long-Term Results of the First Clinical Application of Stereotactic Radioablation Using a Linear Electron Accelerator for the Treatment of Ventricular Tachycardia.

We present the first clinical application of non-invasive stereotaxic radioablation of ventricular tachycardia (VT) refractory to medical and surgical treatment. Based on the results of invasive navigational activation mapping, a pericicatrical zone in the interventricular septum associated with VT was verified. Radiosurgical irradiation of the target in the region of the interventricular septum and the posterior apical segment of the left ventricle was performed on a TrueBeam linear electron accelerator (Varian) in accordance with the segmental scheme of the left ventricle. Irradiation doses for 95% of the internal target volume (ITV, 17 cm3) and planned target volume (PTV, 46 cm3) (31.2 and 25 Gy, respectively) were delivered by two full coplanar arches in 1 session. Irradiation was performed during expiration using a respiratory control system. The loading dose to critical structures was within tolerance. The planned follow-up period is 6 months. According to remote monitoring, the intensity of VT paroxysms over 48 days after treatment was from daily to 2-3 per day. Then, the incidence of VT paroxysms decreased (1-3 per week), and from the 64th to the 185th day (the end of the observation period), no VT paroxysms were recorded, which suggests that the impact was highly precise, conformal, and involved the total wall thickness. No undesirable effects and damage to adjacent organs were observed.

Development of Noninvasive Technology of Stereotaxic Radioablation Using Linear Accelerators for the Treatment of Life-Threatening Ventricular Tachycardias in Experiment.

We developed a new technique of noninvasive stereotactic radioablation for the treatment of life-threatening tachyrhythmias. The study is performed on pigs (Sus scrofa domesticus). The zones of planned exposure were atrioventricular node (heart loading dose 40 Gy) and the apex of the left ventricle with a part of the interventricular septum (35 Gy) in animal No. 1 and atrioventricular node (45 Gy) and free wall of the left ventricle (40 Gy) in animal No. 2. The study was conducted on the Varian TrueBeam linear accelerator. The planned follow-up duration was 6 months. Delivery of 40 Gy to the atrioventricular node did not lead to persistent electrophysiological effect due to the development of transient third-degree atrioventricular block. The dose of 45 Gy resulted in permanent third-degree atrioventricular block followed by development of ventricular standstill on day 21 of observation. Histological examination confirmed transmurality and high precision of performed intervention.

Characterizing cardiac contractile motion for noninvasive radioablation of ventricular tachycardia.

Background: Respiratory motion management strategies are used to minimize the effects of breathing on the precision of stereotactic ablative radiotherapy for ventricular tachycardia, but the extent of cardiac contractile motion of the human heart has not been systematically explored. Objective: We aim to assess the magnitude of cardiac contractile motion between different directions and locations in the heart. Methods: Patients with intracardiac leads or valves who underwent 4-dimensional cardiac computed tomography (CT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. The displacement of transvenous right atrial appendage, right ventricular (RV) implantable cardioverter-defibrillator, coronary sinus lead tips, and prosthetic cardiac devices across the cardiac cycle were measured in orthogonal 3-dimensional views on a maximal-intensity projection CT reconstruction. Results: A total of 31 preablation cardiac 4-dimensional cardiac CT scans were analyzed. The LV lead tip had significantly greater motion compared with the RV lead in the anterior-posterior direction (6.0 ± 2.2 mm vs 3.8 ± 1.7 mm; P = .01) and superior-inferior direction (4.4 ± 2.9 mm vs 3.5 ± 2.0 mm; P = .049). The prosthetic aortic valves had the least movement of all fiducials, specifically compared with the RV lead tip in the left-right direction (3.2 ± 1.2 mm vs 6.1 ± 3.8 mm, P = .04) and the LV lead tip in the anterior-posterior direction (3.8 ± 1.7 mm vs 6.0 ± 2.2 mm, P = .03). Conclusion: The degree of cardiac contractile motion varies significantly (1 mm to 15.2 mm) across different locations in the heart. The effect of contractile motion on the precision of radiotherapy should be assessed on a patient-specific basis.

Stereotactic radiotherapy for ventricular tachycardia: A study protocol.

Background: Currently, the standard curative treatment for ventricular tachycardia (VT) and ventricular fibrillation (VF) is radiofrequency catheter ablation. However, when the VT circuit is deep in the myocardium, the catheter may not be delivered, and a new, minimally invasive treatment using different energies is desired. Methods: This is a protocol paper for a feasibility study designed to provide stereotactic radiotherapy for refractory VT not cured by catheter ablation after at least one catheter ablation. The primary end point is to evaluate the short-term safety of this treatment and the secondary endpoint is to evaluate its efficacy as assessed by the reduction in VT episode. Cyberknife M6 radiosurgery system will be used for treatment, and the prescribed dose to the target will be 25Gy in one fraction. The study will be conducted on three patients. Conclusion: Since catheter ablation is the only treatment option for VT that is covered by insurance in Japan, there is currently no other treatment for VT/VF that cannot be cured by catheter ablation. We hope that this feasibility study will provide hope for patients who are currently under the stress of ICD activation. Trial registration: The study has been registered in the Japan Registry of Clinical Trials (jRCTs042230030).

Case Report: Treatment Planning Study to Demonstrate Feasibility of Transthoracic Ultrasound Guidance to Facilitate Ventricular Tachycardia Ablation With Protons.

Background: Cardiac arrhythmias, such as ventricular tachycardia, are disruptions in the normal cardiac function that originate from problems in the electrical conduction of signals inside the heart. Recently, a non-invasive treatment option based on external photon or proton beam irradiation has been used to ablate the arrhythmogenic structures. Especially in proton therapy, based on its steep dose gradient, it is crucial to monitor the motion of the heart in order to ensure that the radiation dose is delivered to the correct location. Transthoracic ultrasound imaging has the potential to provide guidance during this treatment delivery. However, it has to be noted that the presence of an ultrasound probe on the chest of the patient introduces constraints on usable beam angles for both protons and photon treatments. This case report investigates the possibility to generate a clinically acceptable proton treatment plan while the ultrasound probe is present on the chest of the patient. Case: A treatment plan study was performed based on a 4D cardiac-gated computed tomography scan of a 55 year-old male patient suffering from refractory ventricular tachycardia who underwent cardiac radioablation. A proton therapy treatment plan was generated for the actual treatment target in presence of an ultrasound probe on the chest of this patient. The clinical acceptability of the generated plan was confirmed by evaluating standard target dose-volume metrics, dose to organs-at-risk and target dose conformity and homogeneity. Conclusion: The generation of a clinically acceptable proton therapy treatment plan for cardiac radioablation of ventricular tachycardia could be performed in the presence of an ultrasound probe on the chest of the patient. These results establish a basis and justification for continued research and product development for ultrasound-guided cardiac radioablation.

Renal Denervation by Noninvasive Stereotactic Radiotherapy Induces Persistent Reduction of Sympathetic Activity in a Hypertensive Swine Model.

Background We have previously reported the feasibility of noninvasive stereotactic body radiotherapy (SBRT) as a novel approach for renal denervation. Methods and Results Herein, from a translational point of view, we assessed the antihypertensive effect and chronological evolution of SBRT-induced renal nerve injury within 6 months in a hypertensive swine model. Hypertension was induced in swine by subcutaneous implantation of deoxycorticosterone acetate pellets in combination with a high-salt diet. A single dose of 25 Gy with SBRT was delivered for renal denervation in 9 swine within 3.4±1.0 minutes. Blood pressure levels at baseline and 1 and 6 months post-SBRT were comparable to control (n=5), whereas renal norepinephrine was significantly lower at 6 months (P<0.05). Abdominal computed tomography, performed before euthanasia and renal function assessment, remained normal. Standard semiquantitative histological assessment showed that compared with control (1.4±0.4), renal nerve injury was greater at 1 month post-SBRT (2.3±0.3) and peaked at 6 months post-SBRT (3.2±0.8) (P<0.05), along with a higher proportion of active caspase-3-positive nerves (P<0.05). Moreover, SBRT resulted in continuous dysfunction of renal sympathetic nerves and low level of nerve regeneration in 6 months by immunohistochemistry analysis. Conclusions SBRT delivering 25 Gy for renal denervation was safe and related to sustained reduction of sympathetic activity by aggravating nerve damage and inhibiting nerve regeneration up to 6 months; however, its translation to clinical trial should be cautious because of the negative blood pressure response in the deoxycorticosterone acetate-salt hypertensive swine model.

Use of Stereotactic Radioablation Therapy as a Bailout Therapy for Refractory Ventricular Tachycardia in a Patient with a No-entry Left Ventricle.

In patients with mechanical aortic and mitral valves and left ventricular (LV) tachycardia (VT), catheter ablation is technically challenging due to the limited access to the LV. Promising new alternatives to radiofrequency ablation include pulsed-field electroporation, percutaneous or surgical sympathetic neuromodulation, and noninvasive stereotactic radioablation therapy (SBRT). We herein describe the effect of SBRT as a bailout therapy on the management of a challenging VT case in the presence of double left-sided mechanical valves.

Noninvasive Stereotactic Radiotherapy for Renal Denervation in a Swine Model.

BACKGROUND: Catheter-based renal denervation (RDN) has achieved promising outcomes to treat hypertension in recent randomized controlled trials. OBJECTIVES: The purpose of this study was to assess the feasibility, efficacy, and safety of noninvasive stereotactic body radiotherapy (SBRT) as an approach for RDN. METHODS: SBRT was performed in 24 renal arteries from 12 normotensive swine at doses of 25, 35, and 45 Gy (n = 4 each), and an additional 4 swine served as controls. Blood pressure (BP), renal function, and serum norepinephrine (NE) values were obtained at baseline and at 7 days, 1 month, and 3 months after SBRT. Abdominal contrast-enhanced computed tomography (CT) was performed after 3 months before euthanasia. Renal NE concentration was determined, and histological analysis and immunohistochemistry against tyrosine hydroxylase were performed. RESULTS: SBRT procedure was successful in all 12 swine. BP was comparable among groups. Serum and renal NE levels at 3 months were significantly lower in treatment groups compared with control group. Furthermore, SBRT resulted in significantly greater nerve injury score and lower tyrosine hydroxylase score compared with control subjects, whereas there were no statistical differences between SBRT groups. Circumferential lesions created with 35 and 45 Gy were significantly greater than with 25 Gy. CT and histology analysis revealed that animals receiving 35 and 45 Gy experienced more collateral damage, which was minimal in the 25-Gy group. CONCLUSIONS: Noninvasive SBRT was feasible and effective for complete, circumferential RDN in a swine model, with dosage at 25 Gy providing the safest short-term profile.