Multimodal fusion workflow for target delineation in cardiac radioablation of ventricular tachycardia.

BACKGROUND: Cardiac radioablation (CR) is an innovative treatment to ablate cardiac arrythmia sources by radiation therapy. CR target delineation is a challenging task requiring the exploitation of highly different imaging modalities, including cardiac electro-anatomical mapping (EAM). PURPOSE: In this work, a data integration process is proposed to alleviate the tediousness of CR target delineation by generating a fused representation of the heart, including all the information of interest resulting from the analysis and registration of electro-anatomical data, PET scan and planning computed tomography (CT) scan. The proposed process was evaluated by cardiologists during delineation trials. METHODS: The data processing pipeline was composed of the following steps. The cardiac structures of interest were segmented from cardiac CT scans using a deep learning method. The EAM data was registered to the cardiac CT scan using a point cloud based registration method. The PET scan was registered using rigid image registration. The EAM and PET information, as well as the myocardium thickness, were projected on the surface of the 3D mesh of the left ventricle. The target was identified by delineating a path on this surface that was further projected to the thickness of the myocardium to create the target volume. This process was evaluated by comparison with a standard slice-by-slice delineation with mental EAM registration. Four cardiologists delineated targets for three patients using both methods. The variability of target volumes, and the ease of use of the proposed method, were evaluated. RESULTS: All cardiologists reported being more confident and efficient using the proposed method. The inter-clinician variability in delineated target volume was systematically lower with the proposed method (average dice score of 0.62 vs. 0.32 with a classical method). Delineation times were also improved. CONCLUSIONS: A data integration process was proposed and evaluated to fuse images of interest for CR target delineation. It effectively reduces the tediousness of CR target delineation, while improving inter-clinician agreement on target volumes. This study is still to be confirmed by including more clinicians and patient data to the experiments.

Cardiac stereotactic radiation therapy for refractory ventricular arrhythmias in patients with left ventricular assist devices.

Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure refractory to medical therapy. However, the incidence of ventricular arrhythmias (VAs) is high in this population, both in the acute and delayed phases after implantation. About one-third of patients implanted with an LVAD will experience sustained VAs, predisposing these patients to worse outcomes and complicating patient management. The combination of pre-existing myocardial substrate and complex electrical remodeling after LVAD implantation account for the high incidence of VAs observed in this population. LVAD patients presenting VAs refractory to antiarrhythmic therapy and catheter ablation procedures are not rare. In such patients, treatment options are extremely limited. Stereotactic body radiation therapy (SBRT) is a technique that delivers precise and high doses of radiation to highly defined targets, reducing exposure to adjacent normal tissue. Cardiac SBRT has recently emerged as a promising alternative with a growing number of case series reporting the effectiveness of the technique in reducing the VA burden in patients with arrhythmias refractory to conventional therapies. The safety profile of cardiac SBRT also appears favorable, even though the current clinical experience remains limited. The use of cardiac SBRT for the treatment of refractory VAs in patients implanted with an LVAD are even more scarce. This review summarizes the clinical experience of cardiac SBRT in LVAD patients and describes technical considerations related to the implementation of the SBRT procedure in the presence of an LVAD.

Noninvasive cardiac radioablation for ventricular tachycardia: dosimetric comparison between linear accelerator- and robotic CyberKnife-based radiosurgery systems.

BACKGROUND: Few dosimetric comparisons have been published between linear accelerator (LA)-based systems and CyberKnife (CK)-based robotic radiosurgery systems for cardiac radio-ablation in ventricular tachycardia. This study aimed to compare the dosimetry of noninvasive cardiac radio-ablation deliverable on LA with that on CK. METHODS: Thirteen patients who underwent noninvasive cardiac radio-ablation by LA were included. The prescribed dose was 25 Gy in 1 fraction, and the average planning target volume was 49.8 ± 31.0 cm3 (range, 14.4-93.7 cm3). CK plans were generated for comparison. RESULTS: Both the CK and LA plans accomplished appropriate dose coverage and normal tissue sparing. Compared with the LA plans, the CK plans achieved significantly lower gradient indices (3.12 ± 0.71 vs. 3.48 ± 0.55, p = 0.031) and gradient measures (1.00 ± 0.29 cm vs. 1.17 ± 0.29 cm, p < 0.001). They had similar equivalent conformity indices (CK vs. LA: 0.84 ± 0.08 vs. 0.87 ± 0.07, p = 0.093) and maximum doses 2 cm from the planning target volume (PTV) in any direction (CK vs. LA: 50.8 ± 9.9% vs. 53.1 ± 5.3%, p = 0.423). The dosimetric advantages of CK were more prominent in patients with a PTV of ≤ 50 cm3 or a spherical PTV. In patients with a PTV of > 50 cm3 or a non-spherical PTV, the LA and CK plans were similar regarding dosimetric parameters. CK plans involved more beams (232.2 ± 110.8 beams vs. 10.0 ± 1.7 arcs) and longer treatment times (119.2 ± 43.3 min vs. 22.4 ± 1.6 min, p = 0.007). CONCLUSIONS: Both CK and LA are ideal modalities for noninvasive cardiac radio-ablation. Upfront treatment should be considered based on clinical intent.

Dose escalation for stereotactic arrhythmia radioablation of recurrent ventricular tachyarrhythmia - a phase II clinical trial.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is delivered with a planning target volume (PTV) prescription dose of 25 Gy, mostly to the surrounding 75-85% isodose line. This means that the average and maximum dose received by the target is less than 35 Gy, which is the minimum threshold required to create a homogenous transmural fibrosis. Similar to catheter ablation, the primary objective of STAR should be transmural fibrosis to prevent heterogenous intracardiac conduction velocities and the occurrence of sustained ventricular arrhythmias (sVA) caused by reentry. We hypothesize that the current dose prescription used in STAR is inadequate for the long-term prevention of sVA and that a significant increase in dose is necessary to induce transmural scar formation. OBJECTIVE: A single arm, multi-center, phase II, dose escalation prospective clinical trial employing the i3 + 3 design is being conducted to examine the safety of a radiation dose-escalation strategy aimed at inducing transmural scar formation. The ultimate objective of this trial is to decrease the likelihood of sVA recurrence in patients at risk. METHODS: Patients with ischemic or non-ischemic cardiomyopathy and recurrent sVA, with an ICD and history of ≥ 1 catheter ablation for sVA will be included. This is a prospective, multicenter, one-arm, dose-escalation trial utilizing the i3 + 3 design, a modified 3 + 3 specifically created to overcome limitations in traditional dose-finding studies. A total of 15 patients will be recruited. The trial aims to escalate the ITV dose from 27.0 Gy to an ITV prescription dose-equivalent level of maximum 35.1 Gy by keeping the PTV prescription dose constant at 25 Gy while increasing the dose to the target (i.e. the VT substrate without PTV margin) by step-wise reduction of the prescribing isodose line (85% down to 65%). The primary outcome of this trial is safety measured by registered radiation associated adverse events (AE) up to 90 days after study intervention including radiation associated serious adverse events graded as at least 4 or 5 according to CTCAE v5, radiation pneumonitis or pericarditis requiring hospitalization and decrease in LVEF ≥ 10% as assessed by echocardiography or cardiac MRI at 90 days after STAR. The sample size was determined assuming an acceptable primary outcome event rate of 20%. Secondary outcomes include sVA burden at 6 months after STAR, time to first sVA recurrence, reduction in appropriate ICD therapies, the need for escalation of antiarrhythmic drugs, non-radiation associated safety and patient reported outcome measures such as SF-36 and EQ5D. DISCUSSION: DEFT-STAR is an innovative prospective phase II trial that aims to evaluate the optimal radiation dose for STAR in patients with therapy-refractory sVA. The trial has obtained IRB approval and focuses on determining the safe and effective radiation dose to be employed in the STAR procedure. TRIAL REGISTRATION: NCT05594368.

A target definition based on electroanatomic maps for stereotactic arrhythmia radioablation.

PURPOSE: Identifying the target region is critical for successfully treating ventricular tachycardia (VT) with single fraction stereotactic arrhythmia radioablation (STAR). We report the feasibility of target definition based on direct co-registration of electroanatomic maps (EAM) and radioablation planning images. MATERIALS AND METHODS: The EAM consists of 3D cardiac anatomy representation with electrical activity at endocardium and is acquired by a cardiac electrophysiologist (CEP) during electrophysiology study. The CEP generates an EAM using a 3D cardiac mapping system anticipating radioablation planning. Our in-house software read these non-DICOM EAMs, registered them to a planning image set, and converted them to DICOM structure files. The EAM based target volume was finalized based on a consensus of CEPs, radiation oncologists and medical physicists, then expanded to ITV and PTV. The simulation, planning, and treatment is performed with a standard STAR technique: a single fraction of 25 Gy using volumetric-modulated arc therapy or dynamic conformal arc therapy depending on the target shape. RESULTS: Seven patients with refractory VT were treated by defining the target based on registering EAMs on the planning images. Dice similarity indices between reference map and reference contours after registration were 0.814 ± 0.053 and 0.575 ± 0.199 for LV and LA/RV, respectively. CONCLUSIONS: The quality of the transferred EAMs on the MR/CT images was sufficient to localize the treatment region. Five of 7 patients demonstrated a dramatic reduction in VT events after 6 weeks. Longer follow-up is required to determine the true safety and efficacy of this therapy using EAM-based direct registration method.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Electroanatomical mapping after cardiac radioablation for treatment of incessant electrical storm: a case report from the RAVENTA trial.

BACKGROUND: Electroanatomical mapping (EAM)-guided stereotactic arrhythmia radioablation (STAR) is a novel noninvasive therapy option for patients with monomorphic ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or urgent catheter ablation (CA). Data on success rates in an emergency situation such as electrical storm (ES) are rare. We present a case of a patient with an initially very poor life expectancy after extensive myocardial infarction with therapy-resistant ES, not amendable for further antiarrhythmic drug therapy, implantable cardioverter-defibrillator implantation, or repeated CA who was introduced to the radiation oncology department for emergency STAR as a bail-out therapy. METHODS: Target volume definition and transfer from EAM to CT were validated and quality assured with a semi-automatic, dedicated visualization tool (CARDIO-RT). Emergency STAR was performed with 25 Gy in the framework of the RAVENTA study. The VT burden gradually decreased after STAR; however, a second VT morphology occurred, which was successfully treated with EAM-guided CA 12 days after STAR. RESULTS: The second EAM-guided CA showed areas of low voltage in the irradiated segments, indicating a precise targeting and early functional response to STAR. The patient remained free of any VT recurrence or any radiation-related toxicities and in good general condition during the recent follow-up of 18 months. CONCLUSION: The case highlights the possible approach, caveats, difficulties, and prognosis of a patient severely affected by therapy-resistant VT in whom CA could not lead to VT suppression. Further studies of putative mechanisms of STAR in the acute and chronic phase of this novel therapy are warranted.

From organ at risk to target organ: Dosimetric comparison of myocardial stereotactic ablative body radiotherapy between helical tomotherapy and volumetric arc therapy for refractory ventricular tachycardia.

Ventricular tachycardia (VT) is an important type of arrhythmia with a risk of sudden death. Although implanted cardiac defibrillation and radiofrequency ablation are used together with medical treatments for VT, the treatment options are limited in cases that do not respond to them. Stereotactic ablative body radiotherapy (SABR) applied to VT substrates in resistant cases is an emerging treatment with positive results. Such clinical results have increased the interest in this subject. However, the ideal treatment device and method have not yet been described for this therapy, which is generally applied at a single fraction using various devices and methods. Herein, treatment planning was conducted for a total of 8 patients (11 VT substrates) using the Varian TrueBeam EDGE and TomoTherapy Radixact devices at a single center, and the results were compared dosimetrically. The Wilcoxon-signed rank test was used for the statistical analysis, and mean values were expressed as medians and interquartile ranges (IQRs). In the volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT) plans, the plan coverages and conformity indexes were similar; meanwhile, the homogeneity indexes were 0.10 (IQR = 0.05) and 0.07 (IQR = 0.05), respectively, and were significantly better in the HT plan (p = 0.02). The gradient indexes were 3.18 (IQR = 0.8) and 5.33 (IQR = 3.68) in the VMAT and HT plans, respectively, and were significantly better in the VMAT plan. For the organs at risk, similar doses were observed. The maximum doses for the stomach and esophagus and the mean doses for the left lung and both lungs were significantly lower in the VMAT plan. Similarly, the maximum and mean doses for the cardiac substructures and great vessels were significantly lower in the VMAT plan. More homogeneous plans were obtained in HT, while a faster dose reduction and lower critical organ dose were observed in VMAT. Reasonable myocardial SABR plans could be obtained with both techniques. The effects of the dosimetric differences on the clinical outcomes should be evaluated in prospective clinical studies.

Radiosurgery for ventricular tachycardia (RAVENTA): interim analysis of a multicenter multiplatform feasibility trial.

BACKGROUND: Single-session cardiac stereotactic radiation therapy (SBRT) has demonstrated promising results for patients with refractory ventricular tachycardia (VT). However, the full safety profile of this novel treatment remains unknown and very limited data from prospective clinical multicenter trials are available. METHODS: The prospective multicenter multiplatform RAVENTA (radiosurgery for ventricular tachycardia) study assesses high-precision image-guided cardiac SBRT with 25 Gy delivered to the VT substrate determined by high-definition endocardial and/or epicardial electrophysiological mapping in patients with refractory VT ineligible for catheter ablation and an implanted cardioverter defibrillator (ICD). Primary endpoint is the feasibility of full-dose application and procedural safety (defined as an incidence of serious [grade ≥ 3] treatment-related complications ≤ 5% within 30 days after therapy). Secondary endpoints comprise VT burden, ICD interventions, treatment-related toxicity, and quality of life. We present the results of a protocol-defined interim analysis. RESULTS: Between 10/2019 and 12/2021, a total of five patients were included at three university medical centers. In all cases, the treatment was carried out without complications. There were no serious potentially treatment-related adverse events and no deterioration of left ventricular ejection fraction upon echocardiography. Three patients had a decrease in VT episodes during follow-up. One patient underwent subsequent catheter ablation for a new VT with different morphology. One patient with local VT recurrence died 6 weeks after treatment in cardiogenic shock. CONCLUSION: The interim analysis of the RAVENTA trial demonstrates early initial feasibility of this new treatment without serious complications within 30 days after treatment in five patients. Recruitment will continue as planned and the study has been expanded to further university medical centers. TRIAL REGISTRATION NUMBER: NCT03867747 (clinicaltrials.gov). Registered March 8, 2019. Study start: October 1, 2019.

A Meta-analysis of the Efficacy and Safety of Stereotactic Arrhythmia Radioablation (STAR) in Patients with Refractory Ventricular Tachycardia.

AIMS: Reports of stereotactic arrhythmia radioablation (STAR) in patients with refractory ventricular tachycardia after catheter ablation are limited to small series. Here, we carried out a systematic review and meta-analysis of studies to better determine the efficacy and toxicity of STAR for ventricular tachycardia. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines, eligible studies were identified on Medline, Embase, Cochrane Library and the proceedings of annual meetings to 10 February 2023. Efficacy was defined as a ventricular tachycardia burden reduction >70% at 6 months; safety was defined as <10% of any grade ≥3 toxicity. RESULTS: Seven observational studies with a total of 61 patients treated were included. At 6 months, the ventricular tachycardia burden reduction was 92% (95% confidence interval 85-100%) and use of fewer than two anti-arrhythmic drugs was seen in 85% (95% confidence interval 50-100). Six months after STAR, an 86% reduction (95% confidence interval 80-93) in the number of implantable cardioverter-defibrillator shocks was observed. The rates for improved, unchanged and decreased cardiac ejection fraction were 10%, 84% and 6%, respectively. Overall survival at 6 and 12 months was 89% (95% confidence interval 81-97) and 82% (95% confidence interval 65-98). The cardiac-specific survival at 6 months was 87%. Late grade 3 toxicity occurred in 2% (95% confidence interval 0-5%) with no grade 4-5 toxicity. CONCLUSION: STAR demonstrated both satisfactory efficacy and safety for the management of refractory ventricular tachycardia and was also associated with a significant decline in anti-arrhythmic drugs consumption. These findings support the continued development of STAR as a treatment option.

Non-invasive stereotactic arrhythmia radiotherapy for ventricular tachycardia: results of the prospective STARNL-1 trial.

AIMS: Stereotactic arrhythmia radiotherapy (STAR) is suggested as potentially effective and safe treatment for patients with therapy-refractory ventricular tachycardia (VT). However, the current prospective knowledge base and experience with STAR is limited. In this study we aimed to prospectively evaluate the efficacy and safety of STAR. METHODS AND RESULTS: The StereoTactic Arrhythmia Radiotherapy in the Netherlands no.1 was a pre-post intervention study to prospectively evaluate efficacy and safety of STAR. In patients with therapy-refractory VT, the pro-arrhythmic region was treated with a 25 Gy single radiotherapy fraction. The main efficacy measure was a reduction in the number of treated VT-episodes by ≥50%, comparing the 12 months before and after treatment (or end of follow-up, excluding a 6-week blanking period). The study was deemed positive when ≥50% of patients would meet this criterion. Safety evaluation included left ventricular ejection fraction, pulmonary function, and adverse events. Six male patients with an ischaemic cardiomyopathy were enrolled, and median age was 73 years (range 54-83). Median left ventricular ejection fraction was 38% (range 24-52). The median planning target volume was 187 mL (range 93-372). Four (67%) patients completed the 12-month follow-up, and two patients died (not STAR related) during follow-up. The main efficacy measure of ≥50% reduction in treated VT-episodes at the end of follow-up was achieved in four patients (67%). The median number of treated VT-episodes was reduced by 87%. No reduction in left ventricular ejection fraction or pulmonary function was observed. No treatment related serious adverse events occurred. CONCLUSIONS: STAR resulted in a ≥ 50% reduction in treated VT-episodes in 4/6 (67%) patients. No reduction in cardiac and pulmonary function nor treatment-related serious adverse events were observed during follow-up. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register-NL7510.

Cardiac radioablation of incessant ventricular tachycardia in patients with terminal heart failure under permanent left ventricular assist device therapy-description of two cases.

PURPOSE: Cardiac radioablation (cRA) using a stereotactic single-session radioablative approach has recently been described as a possible treatment option for patients with otherwise untreatable recurrent ventricular tachycardia (VT). There is very limited experience in cRA for patients undergoing left ventricular assist device (LVAD) therapy. We present clinical experiences of two patients treated with cRA for incessant VT under long-term LVAD therapy. METHODS: Two male patients (54 and 61 years old) with terminal heart failure under LVAD therapy (both patients for 8 years) showed incessant VT despite extensive antiarrhythmic drug therapy and repeated catheter ablation. cRA with a single dose of 25 Gy was applied as a last resort strategy under compassionate use in both patients following an electroanatomical mapping procedure. RESULTS: Both patients displayed ongoing VT during and after the cRA procedure. Repeated attempts at post-procedural rhythm conversion failed in both patients; however, one patient was hemodynamically stabilized and could be discharged home for several months before falling prey to a fatal bleeding complication. The second patient initially stabilized for a few days following cRA before renewed acceleration of running VT required bilateral ablation of the stellate ganglion; the patient died 50 days later. No immediate side effects of cRA were detected in either patient. CONCLUSION: cRA might serve as a last resort strategy for patients with terminal heart failure undergoing LVAD therapy and displaying incessant VT. Intermediate- and long-term outcomes of these seriously ill patients often remain poor; therefore, best supportive care strategies should also be evaluated as long as no clear beneficial effects of cRA procedures can be shown. For patients treated with cRA under running ventricular rhythm abnormality, strategies for post-procedural generation of stabilized rhythm have to be established.

Evaluation of the feasibility of cardiac gating for SBRT of ventricular tachycardia based on real-time ECG signal acquisition.

PURPOSE: To investigate the feasibility of cardiac synchronized gating in stereotactic body radiation therapy (SBRT) of ventricular tachycardia (VT) using a real-time electrocardiogram (ECG) signal acquisition. METHODS AND MATERIALS: Stability of beam characteristics during simulated ECG gating was examined by developing a microcontroller interface to a Varian Clinac iX linear accelerator allowing gating at frequencies and duty cycles relevant to cardiac rhythm. Delivery accuracy was evaluated by measuring dose linearity with an ionization chamber, and flatness and symmetry with a two-dimensional detector array, for different gating windows within typical human cardiac cycle periods. To establish a practical method of gating based on actual ECG signals, an AD8232 Heart Monitor board was used to acquire the ECG signal and synchronize the beam delivery. Real-time cardiac gated delivery measurements were performed for a single 10 × 10 cm2 field and for a VT-SBRT plan using intensity-modulated radiation therapy (IMRT). RESULTS AND DISCUSSION: Dose per monitor unit (MU) values were found to be linear within most gating windows investigated with maximum differences relative to non-gated delivery of <2% for gating windows ≥200 ms and for >10 MUs. Beam profiles for both gated and non-gated modes were also found to agree with maximum differences of 0.5% relative to central axis dose for all sets of beam-on/beam-off combinations. Comparison of dose distributions for intensity-modulated SBRT plans between non-gating and cardiac gating modes provided a gamma passing rate of 97.2% for a 2% 2 mm tolerance. CONCLUSIONS: Beam output is stable with respect to linearity, flatness, and symmetry for gating windows within cardiac cycle periods. Agreement between dose distributions for VT-SBRT using IMRT in non-gated and cardiac cycle gated delivery modes shows that the proposed methodology is feasible. Technically, gating for delivery of SBRT for VT is possible with regard to beam stability.

Inflammation and fibrosis characterize different stages of myocardial remodeling in patients after stereotactic body radiotherapy of ventricular myocardium for recurrent ventricular tachycardia.

We performed a histological and immunohistochemical analysis of myocardia from 3 patients who underwent radiosurgery and died for various reasons 3 months to 9 months after radiotherapy. In Case 1 (death 3 months after radiotherapy) we observed a sharp transition between relatively intact and irradiated regions. In the myolytic foci, only scattered cardiomyocytes were left and the area was infiltrated by immune cells. Using immunohistochemistry we detected numerous inflammatory cells including CD68+/CD11c+ macrophages, CD4+ and CD8+ T-lymphocytes and some scattered CD20+ B-lymphocytes. Mast cells were diminished in contrast to viable myocardium. In Case 2 and Case 3 (death 6 and 9 months after radiotherapy, respectively) we found mostly fibrosis, infiltration by adipose tissue and foci of calcification. Inflammatory infiltrates were less pronounced. Our observations are in accordance with animal experimental studies and confirm a progress from myolysis to fibrosis. In addition, we demonstrate a role of pro-inflammatory macrophages in the earlier stages of myocardial remodeling after stereotactic radioablation for ventricular tachycardia.

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).

Stereotactic Radiotherapy in the Management of Ventricular Tachycardias: More Questions than Answers?

Stereotactic body radiotherapy is a recent promising therapeutic alternative in cases of failed catheter ablation for recurrent ventricular tachycardias (VTs) in patients with structural heart disease. Initial clinical experience with a single radiation dose of 25 Gy shows reasonable efficacy in the reduction of VT recurrences with acceptable acute toxicity. Many unanswered questions remain, including unknown mechanism of action, variable time to effect, optimal method of substrate targeting, long-term safety, and definition of an optimal candidate for this treatment."

Stereotactic Radioablation for Ventricular Tachycardia in the Setting of Electrical Storm.

BACKGROUND: Stereotactic body radiotherapy (SBRT) has been reported as a safe and efficient therapy for treating refractory ventricular tachycardia (VT) despite optimal medical treatment and catheter ablation. However, data on the use of SBRT in patients with electrical storm (ES) is lacking. The aim of this study was to assess the clinical outcomes associated with SBRT in the context of ES. METHODS: This retrospective study included patients who underwent SBRT in the context of ES from March 2020 to March 2021 in one tertiary center (CHU Lille). The target volume was delineated according to a predefined workflow. The efficacy was assessed with the following end points: sustained VT recurrence, VT reduced with antitachycardia pacing, and implantable cardioverter defibrillator shock. RESULTS: Seventeen patients underwent SBRT to treat refractory VT in the context of ES (mean 67±12.8 age, 59% presenting ischemic heart disease, mean left ventricular ejection fraction: 33.7± 9.7%). Five patients presented with ES related to incessant VT. Among these 5 patients, the time to effectiveness ranged from 1 to 7 weeks after SBRT. In the 12 remaining patients, VT recurrences occurred in 7 patients during the first 6 weeks following SBRT. After a median 12.5 (10.5-17.8) months follow-up, a significant reduction of the VT burden was observed beyond 6 weeks (-91% [95% CI, 78-103]), P<0.0001). The incidence of implantable cardioverter defibrillator shock and antitachycardia pacing was 36% at 1 year. CONCLUSIONS: SBRT is associated with a significant reduction of the VT burden in the event of an ES; however, prospective randomized control trials are needed. In patients without incessant VT, recurrences are observed in half of patients during the first 6 weeks. VT tolerance and implantable cardioverter defibrillator programming adjustments should be integrated as part of an action plan defined before SBRT for each patient.

Successful Application of Stereotactic Body Radiation Therapy for Ventricular Tachycardia Substrate in a Patient With Nonischemic Cardiomyopathy.

Cardiac stereotactic body radiotherapy (SBRT) has been gaining attention as a potential treatment for patients with ventricular tachycardia (VT). Here, we describe a nonischemic patient with severe heart failure and VTs originating from the deep anteroseptal substrate that was refractory to standard and bipolar catheter ablations, and was successfully managed with SBRT. In conclusion, anteroseptal VTs resistant to catheter ablation in severe nonischemic heart failure might be an indication for cardiac SBRT as palliative therapy.

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the RAdiosurgery for VENtricular TAchycardia (RAVENTA) Trial.

PURPOSE: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the RAdiosurgery for VENtricular TAchycardia trial. METHODS AND MATERIALS: Planning computed tomography data and consensus structures from 3 patients were sent to 5 academic centers for independent plan development using a variety of platforms and techniques with the RAdiosurgery for VENtricular TAchycardia study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for ventricular tachycardia treatments was established. RESULTS: For each case, 3 coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and 3 noncoplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the planning target volume ≥30 Gy ranged from 0.0% to 79.9% and the ramus interventricularis anterior V14Gy ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high-dose region, while the plans for the robotic arm LINAC had smaller low-dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome. CONCLUSIONS: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.