The state‐of‐the‐art technic of stereotactic radioablation for the treatment of cardiac arrhythmias: An overview

Abstract

Introduction

Cardiac arrhythmias, including ventricular tachycardia (VT), stand as a significant threat to health, often leading to mortality and sudden cardiac death. While conventional treatments for VT exhibit efficacy, cases of refractory VT pose challenges. Stereotactic Arrhythmia Radioablation (STAR) offers a novel approach, delivering precise high‐dose radiation to well‐defined targets with minimal collateral damage. This study explores the potential of STAR as an alternative therapy, especially for high‐risk patients or those with refractory VT.

Methods

This research reviews ongoing studies and preliminary investigations into the evaluation of the efficacy and safety of STAR. The method involves targeted radiation delivery, assessing reductions in VT recurrence and the early safety profile in refractory VT patients. However, given STAR's early stage and limited clinical evidence, cautious interpretation is advised.

Results

Preliminary findings indicate a reduction in VT recurrence with STAR, suggesting promise as a therapeutic option. Early safety profiles are encouraging, but definitive statements on efficacy and safety require further investigation. Positive initial outcomes underscore the need for additional data and long‐term studies.

Conclusion

Stereotactic Arrhythmia Radioablation is recently emerging as a promising treatment for refractory VT. While early results are encouraging, careful interpretation is needed, due to STAR's early stages. Ongoing investigations are critical for a comprehensive understanding of its long‐term efficacy and tolerability. This review provides fundamental insights into STAR's background, principles, pre‐treatment procedures, clinical implications, and toxicity, setting the stage for future research in this evolving therapeutic field.

1. INTRODUCTION

Cardiac arrhythmias are a major cause of mortality, morbidity, and sudden cardiac death. ¹ Especially, ventricular tachycardia (VT) is a life‐threatening condition that globally contributes to 4.25 million deaths every year. ² This condition requires intensive intervention to prevent sudden death. The underlying anatomic structures that help initiate or maintain cardiac arrhythmias are largely known. These anatomic substrates may be congenital, or the result of pathological changes in cardiac tissue, such as cardiac tissue scarring after myocardial infarction in many types of VT, or possibly a combination of these mechanisms, as hypothesized in patients with atrial fibrillation (AF). ³ , ⁴

Atrial fibrillation is the most common tachyarrhythmia, affecting approximately 1% of the general population. It has been associated with an increased risk of ischemic stroke, heart failure, and mortality. Current treatment strategies to prevent AF and maintain sinus rhythm include antiarrhythmic drugs (AAD) and pulmonary vein isolation by radiofrequency or cryo‐balloon ablation. Despite recent improvements in treatment of these patients, we have been able to maintain sinus rhythm in only fewer than 80% of patients with paroxysmal AF and even fewer patients with non‐paroxysmal AF. Although ventricular tachyarrhythmias, including ventricular tachycardia (VT) and ventricular fibrillation (VF), are less common than AF, they are highly lethal and require close interventions to prevent SCD ² , ⁵ Current treatments for VT are AADs and catheter ablation of arrhythmogenic substrates. Implantable cardioverter defibrillators (ICDs) are also used to cardiovert the ventricular arrhythmias, if they occur. Despite significant clinical improvement, conventional radiofrequency (RF) ablation does not successfully eliminate VT in some cases, especially in patients with difficult anatomy for this approach or subepicardial substrate location. ⁶ Moreover, the recurrence rate of VT after RF ablation ranges from 10% to 40% during long‐term follow‐up. ⁷ Although RF ablation is rarely associated with any direct procedural complications (0.6%), it is associated with short‐term mortality of up to 5% in patients with ischemic VT. Therefore, ablation of VT is associated with a high risk of procedure‐related complications and death. ⁸ , ⁹

Several potential factors are associated with treatment failure. Inaccessibility of arrhythmogenic tissue and inability to deliver adequate ablation energy transmurally through the ventricular myocardium are common reasons for failures of catheter ablation. ¹⁰ Stereotactic body radiation therapy (SBRT), which delivers precise high‐dose irradiation to specific targets in the body with minimal damage to surrounding tissue, is estimated to have the potential to overcome these problems. SBRT, which has minimal toxic effects, is most commonly used to treat tumors with high rates of successful local control. ¹¹ Recent studies have investigated the use of SBRT in the treatment of cardiac arrhythmias, particularly VT and AF. ¹²

This review presents the basic principles, clinical experience and results on the use of SBRT in the treatment of cardiac arrhythmias, and the potential toxic effects.

2. GENERAL PRINCIPLES AND MECHANISM OF ACTION

Common radiotherapy is usually delivered at lower doses (approximately 2 Gy) and in multiple fractions (daily radiation intervals over 4–8 weeks), which is referred to as “fractionated radiotherapy.” ¹³ Recent advances in this field allow clinicians to administer high doses of radiation in fewer fractions (usually up to 5 fractions; e.g., which is referred to as extreme hypo‐fractionated radiotherapy or radiosurgery in a single session [16–25 Gy in one fraction]). ¹⁴ Thanks to the modern radiation technics, the radiation dose can be precisely directed to the desired target area, while the surrounding normal anatomical tissue receives only a minimal dose. ¹¹ The application of these radiotherapy principles for the treatment of malignancies is referred to as stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy (SABR). The application of ablative radiotherapy for the treatment of cardiac arrhythmias is referred to as stereotactic arrhythmia radioablation (STAR). ¹⁵

In contrast to catheter ablation, which uses radiofrequency (RF) or cryocatheter to heat or freeze the target tissue, the biological rationale for the use of radiotherapy resides in its ability to induce a proapoptotic effect and subsequent necrosis of the arrhythmogenic foci. ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ , ²⁰

In contrast to radiofrequency ablation therapy, where the necrotic lesion develops within seconds to minutes, the effect of radiotherapy develops in days to months. This may play an important role in determining the applications and expectations for radiation therapy technics. ²¹ In addition, ablative radiotherapy is usually an outpatient and noninvasive unpainful procedure that does not require anesthesia or other specific medications. Treatment time varies from 10 to 90 min depending on the device used, target site, and volume. ²²

3. PRE‐TREATMENT

3.1. Mapping

Mapping the anatomic arrhythmia substrate is the crucial step to define the SBRT target volume. There are multiple technics for localization of the arrhythmogenic focus and each department does it according to own expertize and equipment. In general, these technics are divided into anatomical imaging modalities and electrophysiological studies. The combination of these data will help to delineate the arrhythmogenic substrate. Anatomical imaging which are used for this purpose are ECG‐gated computed tomography (CT), contrast‐enhanced cardiac Magnetic Resonance Imaging (MRI), detailed transthoracic echocardiography with particular focus on wall motion, and also nuclear mapping methods, like single‐photon emission computerized tomography (SPECT) and Positron Emission Tomography (PET) scan. In SPECT usually TC99 is used as the radiotracer which localize along scarred myocardium; however, in PET scan, fluorodeoxyglucose is used as the radiotracer which congregates in healthy cells with high metabolic activity while being relatively absent in nonfunctional/scarred myocytes. Cardiac CT and MRI determine scarred focus based on myocardial thickness. Electrophysiological studies such as 12 lead electrocardiography (ECG) and electroanatomic mapping (EAM) are also essential to determine the target volume. Most centers use invasive EAM; in this procedure small electrodes are placed in heart chambers and directly record electrical activity of myocardium which gives valuable information of arrhythmogenic regions. The best result could be achieved by combining anatomical and electrophysiological data. In the consensus made by expertize of STAR in 2021, the minimum modality required to determine the arrhythmogenic substrate were 12 lead ECG, EAM and contrast‐enhanced ECG triggered computed tomography (CT) scan. Once the arrhythmogenic substrate is localized by the data from radiological studies and/or EP mapping, a treatment delivery plan is conducted by the radiation oncologist, radiation physicist, and electrophysiologist. The planning is typically done using specialized SBRT planning software. ²³ , ²⁴ , ²⁵ , ²⁶ , ²⁷ These software however, do not automatically import EAM data into the planning, causing some level of uncertainty in delivery of the STAR. ²⁸

3.2. Cardiorespiratory exercise compensation

Once a radiation treatment plan is approved, cardiorespiratory motion must be considered in treatment planning and delivery. High frequency cardiac movement and respiratory pattern cause complexities in predicting and overcoming movement during the procedure. ²⁸ Several strategies are used for motion management, depending mainly on the treatment device used. ²⁹ , ³⁰ There are currently two main strategies for motion management. One is to minimize motion as much as possible and the other is cardiorespiratory motion tracking. The first method uses an immobilization or compression device; however, a larger target volume is planned to capture the entire target site as seen on a respiratory‐guided CT or a cardiac‐guided CT. ³¹ Respiratory arrest and abdominal compression to limit diaphragmatic motion are examples of active and passive immobilization, respectively. ³⁰ , ³¹ , ³² In the second method, the target is tracked throughout the respiratory cycle, and irradiation is delivered based on respiratory gating and the position of the target in a specific phase of the respiratory cycle. In this method, a reference marker, which may be an existing device component or an implanted Goldseed, serves as a surrogate for the target position and is used to track image motion with X‐ray or CT imaging. This marker also switches the beam path and serves as a trigger to turn the beam on and off as it moves in and out of its preset position. ³³ Another approach is to use a device that can move synchronously and in real time with the target object using an internal motion tracking system. This device allows the accelerator to align the beam with the motion of the target. This latter approach is used by the CyberKnife (Accuray) platform. ³⁴ Akdag et al. also studied this phenomenon in a simulation and concluded that the cardiac motion during the process reduced the D98% dose by 0.1–1.3 Gy. They also observed that Real‐time MRI‐guided motion management reduced this dose uncertainty. ³⁵

3.3. Technical aspects of radiotherapy

3.3.1. Simulation procedure

A simulation CT scan is an imaging procedure performed before radiation treatment to simulate the patient's position during treatment delivery. Due to the novelty of STAR, there is no standard technic, and each center does it according to their own equipment and protocols. However, the cornerstones remain the same. To perform CT simulation, the patient is placed in supine position. Patient's position must be reproducible, while keeping them comfortable during treatment time. In most of the studies, immobilization devices such as a vacuum bag and body fixator were used to provide reproducibility. Moreover, in some studies, abdominal compression was used to minimize respiratory motion. Slice thickness could be in the range of 1–3 mm, but most studies used 1 mm thickness. Planning of the CT simulation must cover the entire treatment volume and the related organs at risk. Intravenous contrast must be used as well, and also in some studies, oral contrast has been used to visualize the gastrointestinal tract better, particularly if the scar is located in the inferior wall of the myocardium. Another critical issue that needs to be considered is respiratory and cardiac motion. Two main strategies exist for motion management. The first one is to acquire a 4‐D CT scan in addition to a free‐breathing CT scan and evaluate scar location during respiratory cycles. These scans are then fused to create an adjusted planning image set. The second option is to use fiducial markers, which is discussed elsewhere in the manuscript.

3.3.2. Target volume delineation and treatment delivery

Defining treatment volume and determining treatment delivery technics requires teamwork and communication between cardiologist, radiation oncologist, medical physicist, and radiation treatment technologists. As mentioned above, before the initiation of target volume delineation, various imaging methods were performed to identify the arrhythmogenic substrate. To define Gross Tumor Volume (GTV), which is the arrhythmogenic focus, electrophysiological data from ECG, EAM, and so on, were merged with anatomical data from cardiac CT/MRI/echocardiography, and so on. An Internal Target Volume (ITV) margin will be added to GTV based on a 4D CT scan to encompass the respiratory and cardiac motion. Finally, Planning Target Volume (PTV) was created by adding a 3–5 mm margin uniformly in all directions to account for setup and delivery uncertainties. Also, related organs at risk (OAR) must be defined and delineated. Dose constraints of relevant OARs like lungs, spinal cord, esophagus, stomach, coronary arteries, and healthy parts of the heart should be considered. In almost all the studies total dose was 25 Gy to 95% of the PTV in one fraction. Treatment duration ranged from 4 to 114 min, depending on the radiotherapy machines. Treatment time with a linear accelerator (LINAC) is much less compared to CyberKnife. Because of the rapid dose fall‐off in the SBRT technic, it is essential to reduce uncertainties as much as possible. To achieve this purpose, it is suggested to do an experimental treatment 1 or 2 days before the final STAR treatment to check all aspects of the treatment delivery. Also, it is essential to use an image‐guided technic, most commonly cone‐beam CT (CBCT), to confirm the patient's position. Some studies also used fiducial markers to follow the respiratory and cardiac movement. Small metal objects could be temporarily placed adjacent to the target volume. However, any other radiologically detectable structures that move in tandem with treatment volume could be used as a fiducial marker as well (e.g., coronary stent, mechanical valves, etc.).

4. CLINICAL IMPLICATION

Currently, STAR is classified as experimental by the Food and Drug Administration (FDA), and its use is limited to conditions in which first and second‐line medical or invasive treatments have failed. The best options for performing STAR are patients who are considered unsuitable for catheter ablation, or who have failed at least one catheter ablation attempt. ³⁶ The ideal patient at this time should either be at particularly high risk for catheter ablation or have had at least one failed catheter ablation attempt, especially if the target tissue is inaccessible due to previous cardiac surgery and the location of the substrate is mid‐myocardial or epicardial. ²¹ , ³⁷ To date, several case reports, case series, and prospective studies have been published in this context. However, there is a great heterogeneity in terms of irradiation technic, planning and mapping, patient selection, follow‐up time, and outcomes. Some studies on the clinical application of stereotactic radiosurgery in the treatment of VT and AF are presented below. The studies are described in Table 1.

Table 1.

Clinical trials of cardiac stereotactic body radioablation for ventricular tachycardia.

Author, date	Type of study	Number of patients, cause	Follow‐up (months)	Result	Toxicity	Treatment volume Clinical Target Vol Internal Target Vol Planning Target Vol
Cuculich, 2017 38	Case series	5, structural heart disease and refractory VT.	12	99.9% fewer total VT episodes compared to baseline	One patient died of stroke three weeks after treatment, although whether this was related to SBRT is unclear, and any association with STAR is unclear. No other acute or late complications.	CTV: combination of the location of the first 10 ms of VT from ECGI and the full myocardial thickness of the associated ventricular scar
						ITV: GTV+ cardiac and resp. movement
						PTV: ITV+ safety margin 5 mm
Robinson, 2019 39	Phase I/II single‐arm prospective clinical trial.	19, 17Patients with refractory VT, 2 patients with PVC cardiomyopathy.	13	94% fewer VT episodes overall in 15/16 evaluable patients.	No acute toxicities, two grade III treatment‐related SAEs (exacerbation of heart failure, pericarditis), no grade IV toxicity.	GTV: the target
						ITV: GTV+ cardiac and resp. movement
						PTV:ITV + 5 mm
Neuwirth, 2019 40	Case series	10, structural heart disease and refractory VT.	28	87.6% reduction in total VT load	Four cases of acute toxicity (nausea), one possible grade III late toxicity (mitral regurgitation), three non‐arrhythmic deaths (1 dementia, 2 HF).	arrhythmogenic substrate was used as the clinical target.
						ITV was calculated with ECG and gated‐CT plus existing ICD was used as surrogate marker of respiratory movement
						No additional margin for PTV
Gianni, 2020 41	prospective	5, refractory scarring‐related VT.	12	VT recurrence in all patients	No acute or early STAR‐related complications. Two patients died of heart failure exacerbation after 10 and 12 months
Lloyd, 2020 42	Case series	10, refractory VT	6	69% reduction in VT burden in 8/10 evaluable patients.	Two patients with mild clinical pneumonitis responded to steroid therapy, and one patient experienced VT requiring resuscitation during STAR treatment.	PTV: expanding the region of scar by 1‐5 mm
Chin, 2021 40	Case series	8, refractory ventricular tachycardia.	7.8	A clinically significant benefit was observed in 33% of patients.	No acute or early STAR‐related complications. Two non‐STAR‐related deaths after 2 months, one of which was unclear.	GTV: target location
						PTV: Expanding target contour with a margin of 6‐8 mm
Carbucicchio 2021 26	Clinical trial (with one arm)	7	6	Reduction in both numbers of “VT episodes” and “shocks” from ICD	No treatment‐related adverse events in 8‐month follow up	Clinical target vol: target scar
						Internal target vol: CTV + heart respiratory motion
						Planning target vol: ITV+ residual uncertainties
Li‐Tong Ho et al. 2021 43	Clinical Trial	7	14.5	VA burden and shocks from ICD significantly decreased.	1 patient died of hepatic failure.	Gross target vol: the target
						ITV: GTV+ breathing and cardiac motion
						PTV: ITV + 5 mm margin
Kurzelowski et al. 2022 27	Case report	2	6	No VT in one patient, transitory increase in VT burden with gradual decrease in one patient.	No noticeable deterioration in LV function was noted, nor any adverse effects of radiosurgery associated with the implanted device.
Akdag et al. 2022 35	Simulation	‐	‐	Cardiac motion decreased D98% from 0.1 to 1.3 Gy. MRI‐guided cardiorespiratory motion management significantly alleviated this issue.	‐	GTV plus surrounding structure were delineated by experienced radiation oncologist and Isotropic PTV margin of 5 mm
Krug et al. 2021 28	review	‐	‐	Studies are limited in number of patients, control groups, length of follow‐up.	No significant adverse effects have been observed; but the duration of follow‐up, according to the authors, is not enough to make an accurate judgment.

Abbreviations: AF, atrial fibrillation; HF, heart failure; PVC, premature ventricular contractions, STAR, stereotactic arrhythmia radioablation; VT, ventricular tachyarrhythmia.

The first case series on the treatment of VT with radioablation was performed by Cuculich et al. in which five patients were treated for refractory VT. The authors reported a 99.9% decrease in VT episodes at 6 weeks from baseline and no complications during an incremental follow‐up period of 46 months. At 12 months, three of the four patients were still alive and were no longer receiving AADs. One of the patients restarted amiodarone at ninth month. Another patient received catheter ablation at fourth week due to incomplete termination of VT, but four ineffective catheter ablations were already performed before radioablation. One of the patients died of stroke 3 weeks after the procedure, although the relationship between this death and STAR was unclear. ³⁸

The first prospective study was conducted in 2018 by Robinson et al. The study was a single‐arm prospective phase I/II trial that enrolled 19 patients with refractory VT after failure of at least one antiarrhythmic drug, failure of at least one catheter ablation, or contraindication to catheter ablation. The main end point, defined as up to 90 days with ≤20% treatment‐related serious adverse events, was achieved in 17 of 19 patients (89.5%). A decrease in VT burden was observed in 17 (94%) of the 18 evaluable patients in the 6 months after treatment. The 50% reduction in VT episodes or premature ventricular contraction burden during 24 h was achieved in 94% of patients. However, 69% of patients experienced VT recurrence before 6 months after treatment. One of the patients died 17 days after the treatment as a result of an accident. Two treatment‐related serious adverse events (SAEs) occurred in this study. These were exacerbation of heart failure (grade III) and pericarditis (grade III), which resulted in hospitalization 65 and 80 days after STAR, respectively. ³⁹ Late results of the study, later presented and discussed at a congress, showed that 12‐ and 24‐month survival rates were 72% and 58%, respectively. During this follow‐up period, seven additional deaths occurred, of which three were unlikely (including an accident, amiodarone toxicity, and VT recurrence) and four deaths were possibly related to STAR (two heart failure and two VT recurrence). In addition, two late SAEs occurred (grade III pericardial effusion at 26 months and grade IV gastropericardial fistula at 28 months). ⁴⁴

Neuwirth et al. reported a case series of 10 patients with structural heart disease and refractory VT and with previous failure of catheter ablation. Myocardial scar location was determined by electroanatomic mapping, and a voltage of <0.5 mV was considered myocardial scar. The site considered for ablation was marked using pace‐mapping or slow‐conduction channels. Electroanatomic maps supplemented by CT imaging in systole and diastole were used to contour the clinical target volume. To compensate for respiration, the existing ICD electrode was used as a marker for cardiac motion. Irradiation was delivered with a CyberKnife system (Accuray Inc) at 25 Gy in a single session. Follow‐up time ranged from 16 to 52 months, with a median of 28 months. ⁴⁰ In this study, an 87.6% reduction in total VT burden was observed after a 90‐day follow‐up period. Two patients did not respond to SBRT, two showed late response at 3 and 6 months, and eight patients experienced VT recurrence, including two cases with increased VT burden compared with baseline. The median follow‐up period was 28 months. During this period, treatment‐related SAE occurred in only one patient, and this was progression of mitral regurgitation. Three deaths occurred that were not considered SAEs and were not due to arrhythmias.

Lloyd et al. published a case series of 10 patients treated with STAR in late 2019. ³⁸ Two patients were excluded because they were unable to receive other treatment options and were transferred to hospice shortly after STAR. Seven of the eight evaluable patients responded to treatment. In this study, a 69% reduction in all VT detected or 94% reduction was achieved after exclusion of non‐responders. Adverse effects of treatment occurred in only one patient, namely a slow VT below the treatment zone during STAR treatment that required resuscitation. However, the relatively low toxicity may be associated with a short follow‐up period (median: 6 months), as many adverse effects may develop later after STAR treatment. ⁴²

Another phase II clinical trial published by Gianni et al. included five patients with New York Heart Association (NYHA) class II heart failure symptoms and refractory cicatricial VT who had failed antiarrhythmic drug therapy and catheter ablation. To visualize the target tissue, a trans‐jugular pacing electrode insertion was used as a marker with contrast‐enhanced CT scans using MultiPlan software. A CyberKnife (Accuray Inc) radiosurgery system was used to deliver 25 Gy to the target tissue. The results of this study showed a remarkable reduction in VT burden in 4 of the 5 patients during the 6‐month follow‐up period. However, VT recurrence occurred in all patients 10–14 months after treatment, requiring prior administration of antiarrhythmic drugs. Although no significant early toxicity was reported in this study, two of the patients died of worsening heart failure during the follow‐up period. ⁴¹

Like the previous study, a recent case series by Chin et al. reported limited efficacy of STAR. The study included eight patients with significant concomitant disease (NYHA class III–IV) treated with doses of less than 25 Gy. The decrease in VT episodes during the 3‐month follow‐up period was not statistically significant (p = 0.24). However, an apparent clinical benefit was observed in three patients (33%), as stated by the authors. ⁴⁵

Li‐Ting Ho et al. in one of the rare clinical trials, during a 14‐month follow‐up, also reported the efficacy of 25‐Gy radioablation in reduction of ventricular arrythmias and ICD shocks in patients with refractory ventricular arrythmias and without notable early or late adverse reactions. ⁴³

In another recent study by Carbucicchio et al. on seven patients who underwent SBRT by 25‐Gy radioablation dose, significant reduction in number of VT episodes and ICD shocks were observed at 3 and 6‐month follow‐up intervals. ²⁶

In one of the most recent studies into this topic, a case report in Poland in 2022, two patients with histories of CAD, heart failure, previous ICD implantation, and radiofrequency ablation were admitted for sustained VT. After utilizing EAM and contrast‐enhanced CT for determination of substrate and target volume, 25 Gy dose was delivered. The patients were then followed for 6 months. One patient demonstrated no recurrence of VT, and the other patient, after a transitory increase in VT burden, demonstrated gradual relief from VT. Neither of the patients developed any complications with LV or ICD function. ²⁷

While many of the older studies demonstrated surprising efficacy in refractory VT, Krug et al. raised the concern that several of the newer studies have demonstrated some level of uncertainty. ²⁸ They also pointed out that based on preclinical studies, they do not expect the 25 Gy dose to create a dense fibrosis comparable to that of the RF ablation; however, the limited number of overall patients studied so far with short follow‐up periods, does not permit us to make certain predictions or deductions. ²⁸

5. ADVERSE EVENTS AND TOXICITY

5.1. Early adverse events

The early side effects of STAR reported in the literature are rare and most were Grade I or II and often subclinical. However, given the small sample sizes of the available studies and the substantial variability in reports of toxicity, any conclusion about the early toxicity of STAR should be drawn with caution. The most common early adverse events reported by Robinson et al. were fatigue, nausea, dizziness, hypotension, and dyspnea. ³⁹ Neuwirth et al. observed nausea in 40% of patients, although they used a small planning target volume. ⁴⁰ On the other hand, Gianni et al. found no acute or early adverse events associated with radiation despite the larger planning target volume. ⁴¹ One case of slow VT below the treatment zone requiring resuscitation was also described as an early adverse event by Lloyd et al. ⁴² Carbucicchio et al. observed three non‐SBRT‐related deaths, and the other four patients reached the 6‐month mark without serious events. ²⁶ The two patients in Kurzelowksi et al. also experienced no significant adverse events. ²⁷ In addition to the low risk of clinically significant early adverse events, no significant periprocedural toxicity was observed.

5.2. Late adverse events

To date, only four studies by Neuwirth et al. Robinson et al. Shoji et al. and Qian et al. had a follow‐up of more than 24 months. ³⁹ , ⁴⁰ , ⁴⁶ , ⁴⁷ These four studies reported three SAEs likely related to treatment, including grade III mitral regurgitation progression at 18 months, grade IV gastropericardial fistula at 28 months, and grade III pericardial effusion at 26 months of follow‐up. These significant late adverse events occurred in three cases out of a total of 29 treated patients. Because of the short follow‐up time in most studies, it is likely that the risk of significant late adverse events is underestimated; in particular, the two studies with the largest treatment volumes ⁴¹ , ⁴⁵ had relatively short follow‐up times (median follow‐up 12 and 7.8 months). In our opinion, a randomized clinical trial with a large sample and a longer follow‐up period is needed to investigate the late effects of STAR, especially the risk of worsening heart failure.

6. LIMITATIONS OF THE CURRENT RESEARCH

All the conducted studies had small sample sizes and short‐term follow‐up period. Additionally, the patients enrolled in each study exhibited heterogeneity in terms of performance status, comorbidities, age, heart failure status, and prior antiarrhythmic therapies. Also, patients selected for this treatment approach due to resistance to conventional therapies, potentially introducing a selection bias in patient recruitment. In general, the long‐term effectiveness and safety of this treatment remain uncertain. To gain deeper insights into the role of SBRT, future prospective studies with larger sample sizes and longer follow‐up durations are required.

7. PROSPECTS AND ONGOING CLINICAL TRIALS

Most of the trials and case reports into this field are currently lacking a control arm, lacking sufficient number of patients to make an accurate deduction, and short follow‐up periods to make an accurate judgment on the long‐term efficacy and safety of this method. ²⁸ , ⁴⁸ Since the short‐term and overall safety, together with an acceptable efficacy profile have been observed in the studies so far; we estimate the future studies to be based on randomized trials and controlled comparison to RF ablation and other established methods. This way, we can be more confident in the decision to recommend this method to patients. Moreover, proton therapy has been demonstrated to cover the range of planning target volume in cancers, while delivering lower dose of radiation and possibly reducing side effects such as neuropathy. ⁴⁹ As we have seen the superiority of radioactive ion beams over stable ions, ⁵⁰ we expect that we can benefit from this advantage of proton therapy to improve the outcome and reduce risk of adverse events in management of arrhythmias through radiotherapy technics.

8. CONCLUSION

Clinical evidence regarding the efficacy and safety of STAR in the treatment of cardiac arrhythmias is limited. Most trials in this therapeutic setting have included small sample sizes and short follow‐up periods. The results of the current trials suggest that radiotherapy is a promising treatment modality for patients who are at high risk for catheter ablation or who have refractory VT or AF. Future studies should evaluate the long‐term efficacy, safety, mechanism of action, and optimal radiation protocol of STAR in the treatment of ventricular and atrial arrhythmias.

AUTHOR CONTRIBUTIONS

Farzad MasoudKabir: Conceptualization; Data curation; Project administration; Supervision. Reyhaneh Bayani: Conceptualization; Writing—original draft; Writing—review & editing. Nima Mousavi Darzikolaee: Conceptualization; Writing—original draft. Alireza Abdshah: Supervision; Writing—original draft; Writing—review & editing. Mahsa Moshtaghian: Writing—original draft; Writing—review & editing. Farshid Farhan: Conceptualization; Supervision; Writing—review & editing. Mahdi Aghili: Conceptualization; Writing—original draft; Writing—review & editing. Ali Kazemian: Conceptualization; Data curation; Writing—review & editing. Luca Nicosia: Writing—original draft; Writing—review & editing. Francesco Cuccia: Conceptualization; Data curation; Writing—review & editing. Ana Vitoria Rocha: Writing—review & editing. Fatemeh Jafari: Conceptualization; Data curation; Writing—original draft; Writing—review & editing. Filippo Alongi: Conceptualization; Investigation; Writing—original draft; Writing—review & editing.

CONFLICTS OF INTEREST STATEMENT

There are no conflicts of interest to report. This is a review article. No human subjects were involved, and no consent was needed.

TRANSPARENCY STATEMENT

The lead author Fatemeh Jafari affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

MasoudKabir F, Bayani R, Mousavi Darzikolaee N, et al. The state‐of‐the‐art technic of stereotactic radioablation for the treatment of cardiac arrhythmias: an overview. Health Sci Rep. 2023;6:e1741. 10.1002/hsr2.1741

DATA AVAILABILITY STATEMENT

Data available on request from the authors.