Implementing stereotactic arrhythmia radioablation with STOPSTORM.eu consortium support: intermediate results of a prospective Israeli single-institutional trial.

BACKGROUND: Ventricular tachycardia (VT) is a life-threatening arrhythmia originating from the heart's ventricles. Traditional treatments include antiarrhythmic medications, implantable cardioverter-defibrillators (ICDs), and catheter ablation. Stereotactic body radiation therapy (SBRT) targeting the arrhythmogenic focus in the left ventricle-stereotactic arrhythmia radioablation (STAR)-is an emerging treatment and may offer a potential solution for patients with refractory VT. OBJECTIVE: We designed an interventional prospective clinical trial in Israel aligned with the STOPSTORM.eu consortium's benchmarks, recommendations, and directives to assess the safety and efficacy of STAR in patients with refractory VT. METHODS: Our phase I/II single-institutional trial was approved by the Ministry of Health of Israel for 10 patients, initially assessing safety in the first 3 patients. We included patients with ICDs experiencing symptomatic monomorphic VT after an inadequate response to previous therapies. The primary endpoints were treatment-related serious adverse events and a reduction in VT burden as assessed by ICD interrogation. Secondary outcomes included a reduction in antiarrhythmic medications and changes in quality of life. RESULTS: From August 2023 to August 2024, 3 patients underwent STAR treatment. The prescription dose was a single fraction of 25 Gy. Planning target volumes were 47.8, 49.7, and 91.8 cc, and treatment was successfully delivered with no grade 3 or higher adverse events reported. Over a follow-up period of 12 months for the first patient and 8 months for the second one, no VT events were recorded after treatment. The third patient died from progressive heart failure 3 months after treatment. Left ventricular ejection fraction remained stable, and no significant radiation-induced inflammatory changes were noted. CONCLUSION: The initial results of this trial suggest that STAR can reduce VT episodes in patients with refractory VT without severe adverse effects. The study highlights the importance of international collaboration and standardization in pioneering new treatments. Further follow-up and additional patient data will be necessary to confirm these findings and evaluate long-term outcomes, including potential adjustments to antiarrhythmic medication regimens.

Analysis of left ventricle regional myocardial motion for cardiac radioablation: Left ventricular motion analysis.

PURPOSE: Left ventricle (LV) regional myocardial displacement due to cardiac motion was assessed using cardiovascular magnetic resonance (CMR) cine images to establish region-specific margins for cardiac radioablation treatments. METHODS: CMR breath-hold cine images and LV myocardial tissue contour points were analyzed for 200 subjects, including controls (n = 50) and heart failure (HF) patients with preserved ejection fraction (HFpEF, n = 50), mid-range ejection fraction (HFmrEF, n = 50), and reduced ejection fraction (HFrEF, n = 50). Contour points were divided into segments according to the 17-segment model. For each patient, contour point displacements were determined for the long-axis (all 17 segments) and short-axis (segments 1-12) directions. Mean overall, tangential (longitudinal or circumferential), and normal (radial) displacements were calculated for the 17 segments and for each segment level. RESULTS: The greatest overall motion was observed in the control group-long axis: 4.5 ± 1.2 mm (segment 13 [apical anterior] epicardium) to 13.8 ± 3.0 mm (segment 6 [basal anterolateral] endocardium), short axis: 4.3 ± 0.8 mm (segment 9 [mid inferoseptal] epicardium) to 11.5 ± 2.3 mm (segment 1 [basal anterior] endocardium). HF patients exhibited lesser motion, with the smallest overall displacements observed in the HFrEF group-long axis: 4.3 ± 1.7 mm (segment 13 [apical anterior] epicardium) to 10.6 ± 3.4 mm (segment 6 [basal anterolateral] endocardium), short axis: 3.9 ± 1.3 mm (segment 8 [mid anteroseptal] epicardium) to 7.4 ± 2.8 mm (segment 1 [basal anterior] endocardium). CONCLUSIONS: This analysis provides an estimate of epicardial and endocardial displacement for the 17 segments of the LV for patients with normal and impaired LV function. This reference data can be used to establish treatment planning margin guidelines for cardiac radioablation. Smaller margins may be used for patients with higher degree of impaired heart function, depending on the LV segment.

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 motion and its dosimetric impact during radioablation for refractory ventricular tachycardia.

INTRODUCTION: Cardiac radioablation (CR) is a noninvasive treatment option for patients with refractory ventricular tachycardia (VT) during which high doses of radiation, typically 25 Gy, are delivered to myocardial scar. In this study, we investigate motion from cardiac cycle and evaluate the dosimetric impact in a cohort of patients treated with CR. METHODS: This retrospective study included eight patients treated at our institution who had respiratory-correlated and ECG-gated 4DCT scans acquired within 2 weeks of CR. Deformable image registration was applied between maximum systole (SYS) and diastole (DIAS) CTs to assess cardiac motion. The average respiratory-correlated CT (AVGresp ) was deformably registered to the average cardiac (AVGcardiac ), SYS, and DIAS CTs, and contours were propagated using the deformation vector fields (DVFs). Finally, the original treatment plan was recalculated on the deformed AVGresp CT for dosimetric assessment. RESULTS: Motion magnitudes were measured as the mean (SD) value over the DVFs within each structure. Displacement during the cardiac cycle for all chambers was 1.4 (0.9) mm medially/laterally (ML), 1.6 (1.0) mm anteriorly/posteriorly (AP), and 3.0 (2.8) mm superiorly/inferiorly (SI). Displacement for the 12 distinct clinical target volumes (CTVs) was 1.7 (1.5) mm ML, 2.4 (1.1) mm AP, and 2.1 (1.5) SI. Displacements between the AVGresp and AVGcardiac scans were 4.2 (2.0) mm SI and 5.8 (1.4) mm total. Dose recalculations showed that cardiac motion may impact dosimetry, with dose to 95% of the CTV dropping from 27.0 (1.3) Gy on the AVGresp to 20.5 (7.1) Gy as estimated on the AVGcardiac . CONCLUSIONS: Cardiac CTV motion in this patient cohort is on average below 3 mm, location-dependent, and when not accounted for in treatment planning may impact target coverage. Further study is needed to assess the impact of cardiac motion on clinical outcomes.

Cost of cardiac stereotactic body radioablation therapy versus catheter ablation for treatment of ventricular tachycardia.

AIMS: To compare the cost of cardiac stereotactic body radioablation therapy (SBRT) versus catheter ablation for treating ventricular tachycardia (VT). BACKGROUND: Cardiac SBRT is a novel way of treating refractory VT that may be less costly than catheter ablation, owing to its noninvasive, outpatient nature. However, the true costs of either procedure are not well described, which could help inform a more appropriate reimbursement for cardiac SBRT than simply cross-indexing existing procedural rates. METHODS: Process maps were derived for the full patient care cycle of both procedures using time-driven activity-based costing. Step-by-step timestamps were collected prospectively from a 10-patient SBRT cohort and retrospectively from a 59-patient catheter ablation cohort. Individual costs were estimated by multiplying timestamps with capacity cost rates (CCRs) for personnel, space, equipment, consumable, and indirect resources. These were summed into total cost, which for cardiac SBRT was compared with current catheter ablation and single-fraction lung SBRT reimbursements, both potential reference rates for cardiac SBRT. RESULTS: The direct and total procedural costs of cardiac SBRT ($7549 and $10,621) were 49% and 54% less than those of VT ablation ($14,707 and $23,225). These costs were significantly different from current reimbursement for catheter ablation ($22,692) and lung SBRT ($6329). After including hospitalization expenses (≥$15,000), VT ablation costs at least $27,604 more to furnish than cardiac SBRT. CONCLUSIONS: Time-driven activity-based costing (TDABC) can be a helpful tool for assessing healthcare costs, including novel treatment approaches. In addition to its clinical benefits, cardiac SBRT may provide significant cost reduction opportunities for treatment of VT.

Impact of High-Dose Irradiation on Human iPSC-Derived Cardiomyocytes Using Multi-Electrode Arrays: Implications for the Antiarrhythmic Effects of Cardiac Radioablation.

Cardiac radioablation is emerging as an alternative option for refractory ventricular arrhythmias. However, the immediate acute effect of high-dose irradiation on human cardiomyocytes remains poorly known. We measured the electrical activities of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) upon irradiation with 0, 20, 25, 30, 40, and 50 Gy using a multi-electrode array, and cardiomyocyte function gene levels were evaluated. iPSC-CMs showed to recover their electrophysiological activities (total active electrode, spike amplitude and slope, and corrected field potential duration) within 3-6 h from the acute effects of high-dose irradiation. The beat rate immediately increased until 3 h after irradiation, but it steadily decreased afterward. Conduction velocity slowed in cells irradiated with ≥25 Gy until 6-12 h and recovered within 24 h; notably, 20 and 25 Gy-treated groups showed subsequent continuous increase. At day 7 post-irradiation, except for cTnT, cardiomyocyte function gene levels increased with increasing irradiation dose, but uniquely peaked at 25-30 Gy. Altogether, high-dose irradiation immediately and reversibly modifies the electrical conduction of cardiomyocytes. Thus, compensatory mechanisms at the cellular level may be activated after the high-dose irradiation acute effects, thereby, contributing to the immediate antiarrhythmic outcome of cardiac radioablation for refractory ventricular arrhythmias.

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.

Experimental demonstration of real-time cardiac physiology-based radiotherapy gating for improved cardiac radioablation on an MR-linac.

BACKGROUND: Cardiac radioablation is a noninvasive stereotactic body radiation therapy (SBRT) technique to treat patients with refractory ventricular tachycardia (VT) by delivering a single high-dose fraction to the VT isthmus. Cardiorespiratory motion induces position uncertainties resulting in decreased dose conformality. Electocardiograms (ECG) are typically used during cardiac MRI (CMR) to acquire images in a predefined cardiac phase, thus mitigating cardiac motion during image acquisition. PURPOSE: We demonstrate real-time cardiac physiology-based radiotherapy beam gating within a preset cardiac phase on an MR-linac. METHODS: MR images were acquired in healthy volunteers (n = 5, mean age = 29.6 years, mean heart-rate (HR) = 56.2 bpm) on the 1.5 T Unity MR-linac (Elekta AB, Stockholm, Sweden) after obtaining written informed consent. The images were acquired using a single-slice balance steady-state free precession (bSSFP) sequence in the coronal or sagittal plane (TR/TE = 3/1.48 ms, flip angle = 48 ∘ $^{\circ }$ , SENSE = 1.5, field-of-view = 400 × 207 $\text{field-of-view} = {400}\times {207}$ mm 2 ${\text{mm}}^{2}$ , voxel size = 3 × 3 × 15 $3\times 3\times 15$ mm 3 ${\rm mm}^{3}$ , partial Fourier factor = 0.65, frame rate = 13.3 Hz). In parallel, a 4-lead ECG-signal was acquired using MR-compatible equipment. The feasibility of ECG-based beam gating was demonstrated with a prototype gating workflow using a Quasar MRI4D motion phantom (IBA Quasar, London, ON, Canada), which was deployed in the bore of the MR-linac. Two volunteer-derived combined ECG-motion traces (n = 2, mean age = 26 years, mean HR = 57.4 bpm, peak-to-peak amplitude = 14.7 mm) were programmed into the phantom to mimic dose delivery on a cardiac target in breath-hold. Clinical ECG-equipment was connected to the phantom for ECG-voltage-streaming in real-time using research software. Treatment beam gating was performed in the quiescent phase (end-diastole). System latencies were compensated by delay time correction. A previously developed MRI-based gating workflow was used as a benchmark in this study. A 15-beam intensity-modulated radiotherapy (IMRT) plan ( 1 × 6.25 ${1}\times {6.25}$ Gy) was delivered for different motion scenarios onto radiochromic films. Next, cardiac motion was then estimated at the basal anterolateral myocardial wall via normalized cross-correlation-based template matching. The estimated motion signal was temporally aligned with the ECG-signal, which were then used for position- and ECG-based gating simulations in the cranial-caudal (CC), anterior-posterior (AP), and right-left (RL) directions. The effect of gating was investigated by analyzing the differences in residual motion at 30, 50, and 70% treatment beam duty cycles. RESULTS: ECG-based (MRI-based) beam gating was performed with effective duty cycles of 60.5% (68.8%) and 47.7% (50.4%) with residual motion reductions of 62.5% (44.7%) and 43.9% (59.3%). Local gamma analyses (1%/1 mm) returned pass rates of 97.6% (94.1%) and 90.5% (98.3%) for gated scenarios, which exceed the pass rates of 70.3% and 82.0% for nongated scenarios, respectively. In average, the gating simulations returned maximum residual motion reductions of 88%, 74%, and 81% at 30%, 50%, and 70% duty cycles, respectively, in favor of MRI-based gating. CONCLUSIONS: Real-time ECG-based beam gating is a feasible alternative to MRI-based gating, resulting in improved dose delivery in terms of high γ -pass $\gamma {\text{-pass}}$ rates, decreased dose deposition outside the PTV and residual motion reduction, while by-passing cardiac MRI challenges.

Patient-specific quantification of cardiorespiratory motion for cardiac stereotactic radioablation treatment planning.

Background: Cardiac radioablation is a new treatment for patients with refractory ventricular tachycardia (VT). The target for cardiac radioablation is subject to cardiorespiratory motion (CRM), the heart's movement with breathing and cardiac contraction. Data regarding the magnitude of target CRM are limited but are highly important for treatment planning. Objectives: The study sought to assess CRM amplitude by using ablation catheter geometrical data. Methods: Electroanatomic mapping data of patients undergoing catheter ablation for VT at 3 academic centers were exported. The spatial position of the ablation catheter as a function of time while in contact with endocardium was analyzed and used to quantify CRM. Results: Forty-four patients with ischemic and nonischemic cardiomyopathy and VT contributed 1364 ablation lesions to the analysis. Average cardiac and respiratory excursion were 1.62 ± 1.21 mm and 12.12 ± 4.10 mm, respectively. The average ratio of respiratory to cardiac motion was approximately 11:1. CRM was greatest along the craniocaudal axis (9.66 ± 4.00 mm). Regional variations with respect to respiratory and cardiac motion were observed: basal segments had smaller displacements vs midventricular and apical segments. Patient characteristics (previous cardiac surgery, height, weight, body mass index, and left ventricular ejection fraction) had a statistically significant, albeit clinically moderate, impact on CRM. Conclusion: CRM is primarily determined by respiratory displacement and is modulated by the location of the target and the patient's biometric characteristics. The patient-specific quantification of CRM may allow to decrease treatment volume and reduce radiation exposure of surrounding organs at risk while delivering the therapeutic dose to the target.

Left ventricle segment-specific motion assessment for cardiac-gated radiosurgery.

Purpose.Cardiac radiosurgery is a non-invasive treatment modality for ventricular tachycardia, where a linear accelerator is used to irradiate the arrhythmogenic region within the heart. In this work, cardiac magnetic resonance (CMR) cine images were used to quantify left ventricle (LV) segment-specific motion during the cardiac cycle and to assess potential advantages of cardiac-gated radiosurgery.Methods.CMR breath-hold cine images and LV contour points were analyzed for 50 controls and 50 heart failure patients with reduced ejection fraction (HFrEF, EF < 40%). Contour points were divided into anatomic segments according to the 17-segment model, and each segment was treated as a hypothetical treatment target. The optimum treatment window (one fifth of the cardiac cycle) was determined where segment centroid motion was minimal, then the maximum centroid displacement and treatment area were determined for the full cardiac cycle and for the treatment window. Mean centroid displacement and treatment area reductions with cardiac gating were determined for each of the 17 segments.Results.Full motion segment centroid displacements ranged between 6-14 mm (controls) and 4-11 mm (HFrEF). Full motion treatment areas ranged between 129-715 mm2(controls) and 149-766 mm2(HFrEF). With gating, centroid displacements were reduced to 1 mm (controls and HFrEF), while treatment areas were reduced to 62-349 mm2(controls) and 83-393 mm2(HFrEF). Relative treatment area reduction ranged between 38%-53% (controls) and 26%-48% (HFrEF).Conclusion.This data demonstrates that cardiac cycle motion is an important component of overall target motion and varies depending on the anatomic cardiac segment. Accounting for cardiac cycle motion, through cardiac gating, has the potential to significantly reduce treatment volumes for cardiac radiosurgery.

Stereotactic arrhythmia radioablation (STAR)-A systematic review and meta-analysis of prospective trials on behalf of the STOPSTORM.eu consortium.

Stereotactic arrhythmia radioablation (STAR) is a noninvasive treatment of refractory ventricular tachycardia (VT). In this study, we aimed to systematically review prospective trials on STAR and pool harmonized outcome measures in a meta-analysis. After registration in the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023439666), we searched OVID Medline, OVID Embase, Web of Science Core Collection, the Cochrane Central Register of Controlled Trials, and Google Scholar on November 9, 2023, to identify reports describing results of prospective trials evaluating STAR for VT. Risk of bias was assessed using the Risk Of Bias In Non-randomized Studies of Interventions tool. Meta-analysis was performed using generalized linear mixed models. We identified 10 prospective trials in which 82 patients were treated with STAR between 2016 and 2022. The 90-day rate of treatment-related grade ≥3 adverse events was 0.10 (95% confidence interval [CI] 0.04-0.2). The proportions of patients achieving given VT burden reductions were 0.61 (95% CI 0.45-0.74) for ≥95%, 0.80 (95% CI 0.62-0.91) for ≥75%, and 0.9 (95% CI 0.77-0.96) for ≥50% in 63 evaluable patients. The 1-year overall survival rate was 0.73 (95% CI 0.61-0.83) in 81 patients, 1-year freedom from recurrence was 0.30 (95% CI 0.16-0.49) in 61 patients, and 1-year recurrence-free survival was 0.21 in 60 patients (95% CI 0.08-0.46). Limitations include methodological heterogeneity across studies and moderate to significant risk of bias. In conclusion, STAR is a promising treatment method, characterized by moderate toxicity. We observed 1-year mortality of ≈27% in this population of critically ill patients suffering from refractory VT. Most patients experience a significant reduction in VT burden; however, 1-year recurrence rates are high. STAR should still be considered an investigational approach and recommended to patients primarily within the context of prospective trials.

Stereotactic Arrhythmia Radioablation (STAR): Assessment of cardiac and respiratory heart motion in ventricular tachycardia patients - A STOPSTORM.eu consortium review.

AIM: To identify the optimal STereotactic Arrhythmia Radioablation (STAR) strategy for individual patients, cardiorespiratory motion of the target volume in combination with different treatment methodologies needs to be evaluated. However, an authoritative overview of the amount of cardiorespiratory motion in ventricular tachycardia (VT) patients is missing. METHODS: In this STOPSTORM consortium study, we performed a literature review to gain insight into cardiorespiratory motion of target volumes for STAR. Motion data and target volumes were extracted and summarized. RESULTS: Out of the 232 studies screened, 56 provided data on cardiorespiratory motion, of which 8 provided motion amplitudes in VT patients (n = 94) and 10 described (cardiac/cardiorespiratory) internal target volumes (ITVs) obtained in VT patients (n = 59). Average cardiac motion of target volumes was < 5 mm in all directions, with maximum values of 8.0, 5.2 and 6.5 mm in Superior-Inferior (SI), Left-Right (LR), Anterior-Posterior (AP) direction, respectively. Cardiorespiratory motion of cardiac (sub)structures showed average motion between 5-8 mm in the SI direction, whereas, LR and AP motions were comparable to the cardiac motion of the target volumes. Cardiorespiratory ITVs were on average 120-284% of the gross target volume. Healthy subjects showed average cardiorespiratory motion of 10-17 mm in SI and 2.4-7 mm in the AP direction. CONCLUSION: This review suggests that despite growing numbers of patients being treated, detailed data on cardiorespiratory motion for STAR is still limited. Moreover, data comparison between studies is difficult due to inconsistency in parameters reported. Cardiorespiratory motion is highly patient-specific even under motion-compensation techniques. Therefore, individual motion management strategies during imaging, planning, and treatment for STAR are highly recommended.

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.

Deep learning-based ultrasound transducer induced CT metal artifact reduction using generative adversarial networks for ultrasound-guided cardiac radioablation.

In US-guided cardiac radioablation, a possible workflow includes simultaneous US and planning CT acquisitions, which can result in US transducer-induced metal artifacts on the planning CT scans. To reduce the impact of these artifacts, a metal artifact reduction (MAR) algorithm has been developed based on a deep learning Generative Adversarial Network called Cycle-MAR, and compared with iMAR (Siemens), O-MAR (Philips) and MDT (ReVision Radiology), and CCS-MAR (Combined Clustered Scan-based MAR). Cycle-MAR was trained with a supervised learning scheme using sets of paired clinical CT scans with and without simulated artifacts. It was then evaluated on CT scans with real artifacts of an anthropomorphic phantom, and on sets of clinical CT scans with simulated artifacts which were not used for Cycle-MAR training. Image quality metrics and HU value-based analysis were used to evaluate the performance of Cycle-MAR compared to the other algorithms. The proposed Cycle-MAR network effectively reduces the negative impact of the metal artifacts. For example, the calculated HU value improvement percentage for the cardiac structures in the clinical CT scans was 59.58%, 62.22%, and 72.84% after MDT, CCS-MAR, and Cycle-MAR application, respectively. The application of MAR algorithms reduces the impact of US transducer-induced metal artifacts on CT scans. In comparison to iMAR, O-MAR, MDT, and CCS-MAR, the application of developed Cycle-MAR network on CT scans performs better in reducing these metal artifacts.

Interobserver variability in target definition for stereotactic arrhythmia radioablation.

Background: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR. Methods: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated three predefined segments from the 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume expressed by the root-mean-square of the standard deviation (RMS-SD) over the target volume, and the Dice-coefficient. Results: Ten electrophysiologists completed the study. For the first phase interobserver variability was low as indicated by low variation in distance to the median volume (RMS-SD range: 0.02-0.02 cm) and high Dice-coefficients (mean: 0.97 ± 0.01). In the second phase distance to the median volume was large (RMS-SD range: 0.52-1.02 cm) and the Dice-coefficients low (mean: 0.40 ± 0.15). In the third phase, similar results were observed (RMS-SD range: 0.51-1.55 cm, Dice-coefficient mean: 0.31 ± 0.21). Conclusions: Interobserver variability is high for manual delineation of the VT-target and ventricular segments. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation, for STAR but possibly also for catheter ablation.

Quality assurance process within the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial for the fusion of electroanatomical mapping and radiotherapy planning imaging data in cardiac radioablation.

A novel quality assurance process for electroanatomical mapping (EAM)-to-radiotherapy planning imaging (RTPI) target transport was assessed within the multi-center multi-platform framework of the RAdiosurgery for VENtricular TAchycardia (RAVENTA) trial. A stand-alone software (CARDIO-RT) was developed to enable platform independent registration of EAM and RTPI of the left ventricle (LV), based on pre-generated radiotherapy contours (RTC). LV-RTC were automatically segmented into the American-Heart-Association 17-segment-model and a manual 3D-3D method based on EAM 3D-geometry data and a semi-automated 2D-3D method based on EAM screenshot projections were developed. The quality of substrate transfer was evaluated in five clinical cases and the structural analyses showed substantial differences between manual target transfer and target transport using CARDIO-RT.

Short-term and long-term effects of noninvasive cardiac radioablation for ventricular tachycardia: A single-center case series.

Background: Noninvasive cardiac radioablation is reported to be effective and safe for the treatment of ventricular tachycardia (VT). Objective: This study aimed to analyze the acute and long-term effects of VT radioablation. Methods: Patients with intractable VT or premature ventricular contraction (PVC)-induced cardiomyopathy were included in this study and treated using a single-fraction 25-Gy dose of cardiac radioablation. To quantitatively analyze the acute response after treatment, continuous electrocardiography monitoring was performed from 24 hours before to 48 hours after irradiation and at the 1-month follow-up. Long-term clinical safety and efficacy were assessed 1-year follow-up. Results: From 2019 to 2020, 6 patients were treated with radioablation for ischemic VT (n = 3), nonischemic VT (n = 2), or PVC-induced cardiomyopathy (n = 1). In the short-term assessment, the total burden of ventricular beats decreased by 49% within 24 hours after radioablation and further decreased by 70% at 1 month. The VT component decreased earlier and more dramatically than the PVC component (decreased by 91% and 57% at 1 month, respectively). In the long-term assessment, 5 patients showed complete (n = 3) or partial (n = 2) remission of ventricular arrhythmias. One patient showed recurrence at 10 months, which was successfully suppressed with medical treatment. The posttreatment PVC coupling interval was prolonged (+38 ms at 1 month). Ischemic VT burden decreased more markedly than nonischemic VT burden after radioablation. Conclusion: In this small case series of 6 patients, without a comparison group, cardiac radioablation appeared to decrease the intractable VT burden. A therapeutic effect was apparent within 1-2 days after treatment but was variable by etiology of cardiomyopathy.

Case report: First-in-human combined low-dose whole-heart irradiation and high-dose stereotactic arrhythmia radioablation for immunosuppressive refractory cardiac sarcoidosis and ventricular tachycardia.

Background: Cardiac sarcoidosis is associated with heart failure, conduction abnormalities, and life-threatening arrhythmias including ventricular tachycardia (VT). Radiotherapy has been suggested as a treatment for extra-cardiac sarcoidosis in patients refractory to immunomodulatory treatment. Methods: The effectiveness and safety of low-dose whole-heart radiotherapy for therapy refractory cardiac sarcoidosis were evaluated in a pre- and post-intervention case report comparing the 54 months before and after treatment. Immunomodulatory low-dose whole-heart irradiation as sarcoidosis treatment consisted of a 2 × 2 Gy scheme. Additionally, high-dose single-fraction stereotactic arrhythmia radioablation of 1 × 20 Gy was applied to the pro-arrhythmic region to manage the ventricular tachycardia episodes. Cardiac sarcoidosis disease activity was measured by hypermetabolic areas on repeated fluorodeoxyglucose ([18F]FDG)-PET/computed tomography (CT) scans and by evaluating changes in ventricular tachycardia episodes before and after treatment. Results: One patient with therapy refractory progressive cardiac sarcoidosis and recurrent ventricular tachycardia was treated. The cardiac sarcoidosis disease activity showed a durable regression of inflammatory disease activity from 3 months onwards. The [18F]FDG-PET/CT scan at 54 months did not show any signs of active cardiac sarcoidosis, and a state of remission was achieved. The number of sustained VT episodes was reduced by 95%. We observed that the development of moderate aortic valve regurgitation was likely irradiation-related. No other irradiation-related adverse events occurred, and the left ventricular ejection fraction remained stable. Conclusion: We report here for the first time on the beneficial and lasting effects of combined immunomodulatory low-dose whole-heart radiotherapy and high-dose stereotactic arrhythmia radioablation in a patient with therapy refractory cardiac sarcoidosis and recurrent VT.

Stereotactic arrhythmia radioablation: A multicenter pre-post intervention safety evaluation of the implantable cardioverter-defibrillator function.

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) appears to be beneficial in selected patients with therapy-refractory ventricular tachycardia (VT). However, high-dose radiotherapy used for STAR-treatment may affect functioning of the patients' implantable cardioverter defibrillator (ICD) by direct effects of radiation on ICD components or cardiac tissue. Currently, the effect of STAR on ICD functioning remains unknown. METHODS: A retrospective pre-post multicenter study evaluating ICD functioning in the 12-month before and after STAR was performed. Patients with (non)ischemic cardiomyopathies with therapy-refractory VT and ICD who underwent STAR were included and the occurrence of ICD-related adverse events was collected. Evaluated ICD parameters included sensing, capture threshold and impedance. A linear mixed-effects model was used to investigate the association between STAR, radiotherapy dose and changes in lead parameters over time. RESULTS: In total, 43 patients (88% male) were included in this study. All patients had an ICD with an additional right atrial lead in 34 (79%) and a ventricular lead in 17 (40%) patients. Median ICD-generator dose was 0.1 Gy and lead tip dose ranged from 0-32 Gy. In one patient (2%), a reset occurred during treatment, but otherwise, STAR and radiotherapy dose were not associated with clinically relevant alterations in ICD leads parameters. CONCLUSIONS: STAR treatment did not result in major ICD malfunction. Only one radiotherapy related adverse event occurred during the study follow-up without patient harm. No clinically relevant alterations in ICD functioning were observed after STAR in any of the leads. With the reported doses STAR appears to be safe.

Feasibility of an Automatic Ultrasonographic Image Acquisition System Associated With an Artificial Intelligence Algorithm for Real-Time Monitoring of Cardiac Motion During Cardiac Radio-Ablation.

Background: The management of the cardio-respiratory motion of the target and the reduction of the uncertainties related to patient's positioning are two of the main challenges that stereotactic arrhythmia radio-ablation (STAR) has to overcome. A prototype of a system was developed that can automatically acquire and interpret echocardiographic images using an artificial intelligence (AI) algorithm to calculate cardiac displacement in real-time. Methods: We conducted a single center study enrolling consecutive patients with a history of ventricular arrhythmias (VA) in order to evaluate the feasibility of this automatic acquisition system. Echocardiographic images were automatically acquired from the parasternal and apical views with a dedicated probe. The system was designed to hold the probe fixed to the chest in the supine position during both free-breathing and short expiratory breath-hold sequences, to simulate STAR treatment. The primary endpoint was the percentage of patients reaching a score ≥2 in a multi-parametric assessment evaluating the quality of automatically acquired images. Moreover, we investigated the potential impact of clinical and demographic characteristics on achieving the primary endpoint. Results: We enrolled 24 patients (63 ± 14 years, 21% females). All of them had a history of VA and 21 (88%) had an ICD. Eight patients (33%) had coronary artery disease, 12 (50%) had non-ischemic cardiomyopathy, and 3 had idiopathic VA. Parasternal, as well as apical images were obtained from all patients except from one, in whom parasternal view could not be collected due to the patient's inability to maintain the supine position. The primary endpoint was achieved in 23 patients (96%) for the apical view, in 20 patients (87%) for the parasternal view, and in all patients in at least one of the two views. The images' quality was maximal (i.e., score = 4) in at least one of the two windows in 19 patients (79%). Atrial fibrillation arrhythmia was the only clinical characteristics associated with a poor score outcome in both imaging windows (apical p = 0.022, parasternal p = 0.014). Conclusions: These results provide the proof-of-concept for the feasibility of an automatic ultrasonographic image acquisition system associated with an AI algorithm for real-time monitoring of cardiac motion in patients with a history of VA.