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Stereotactic Radioablation for the Non-Invasive Treatment of Cardiac Arrhythmias: From the Perspective of the Cardiac SBRT Program at Brigham and Women’s Hospital

Pierre C. Qian,BSc(Med) Hons MBBS1,2; William H. Sauer, MD1,2; Ray Mak, MD2,3; Usha B. Tedrow, MD, MS1,2; and Paul C. Zei, MD, PhD1,2

1Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

2Harvard Medical School, Boston, Massachusetts

3Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, Massachusetts

Pierre C. Qian,BSc(Med) Hons MBBS1,2; William H. Sauer, MD1,2; Ray Mak, MD2,3; Usha B. Tedrow, MD, MS1,2; and Paul C. Zei, MD, PhD1,2

1Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts

2Harvard Medical School, Boston, Massachusetts

3Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, Massachusetts

The birth of cardiac catheter ablation in the late 1970s was an inflection point in the world of cardiac electrophysiology. No longer did simple arrhythmias treatable by focal ablation require open surgery. With the advent of radiofrequency ablation, the spectrum of arrhythmias treatable with catheter ablation and the complexity of these procedures has seen unprecedented expansion, assisted by technological advancements.

However, catheter ablation outcomes for ventricular tachycardia (VT) in patients with structural heart disease, while better than antiarrhythmic therapy, have remained suboptimal. Acute procedural success rates in major trials of catheter ablation for spontaneous VT have been 49-75%, with long-term VT-free survival of <50%.1-6 Arrhythmogenic substrates for VT can be extensive and beyond the reach of radiofrequency energy due to biophysical limitations. Consequently, there is active research in alternative energy sources and methods for ablation.   

Stereotactic body radiotherapy (SBRT) is a promising non-invasive cardiac ablation modality that could transform the treatment of VT. The technique is not new — it was developed in the 1950s to treat brain tumors, and has since been applied clinically to treat a range of solid malignancies as well as trigeminal neuralgia. Tissue injury is induced by converging multiple beams of gamma rays that maximize the delivered ionizing radiation dose to the desired target while minimizing dose to collateral structures. At a threshold dose ≥25 Gy, progressive fibrosis and conduction block occurs over months in normal myocardium as demonstrated in animal studies.6-10 While myocytes, being non-dividing cells, are relatively resistant to cell death from radiation, vascular endothelial injury and the ensuing microvascular obstruction and capillary loss, proinflammatory cytokine release, is thought to be important in driving fibrotic replacement.7-10 Anecdotal clinical experience in the treatment of ischemic scar suggests that conduction block may occur much earlier (weeks rather than months), the underlying mechanisms are yet to be fully elucidated but may involve nonlethal effects of radiation on myocyte energy metabolism, calcium handling, or gap junctions.7-10

After Dr. Paul Zei moved to Brigham and Women’s Hospital, bringing his experience with cardiac SBRT for treatment of cardiac arrhythmias, a collaborative effort between our electrophysiology and radiation oncology groups was developed. Our first cardiac SBRT patient was subsequently treated successfully in late 2018. In our current practice, cardiac SBRT has been reserved for treatment of patients with recurrent ventricular tachycardia refractory to catheter ablation. These patients typically have well-characterized VT substrate and arrhythmia mechanisms from electroanatomical mapping and cardiac imaging, but ineffective delivery of radiofrequency energy at critical VT sites. Our cardiac SBRT team consists of electrophysiologists, radiation oncologists, radiation physicists, as well as nursing staff and lab technicians (Figures 1 and 5). The team assesses and consents the patient, plans the radioablative treatment, delivers therapy, and performs clinical follow-up (Figure 2). Significant effort is put into the treatment planning phase, which begins with a synthesis of the electroanatomical map, ECGs, cardiac imaging, clinical history, and other investigations to define an ablation target that encompasses critical VT substrate (Figure 3). Next, we design a planning treatment volume around this ablation target, taking into account cardiorespiratory motion and a safety margin to ensure adequate coverage. Depending on the site of the myocardial scar, the treatment plan is adjusted to ensure nearby structures do not receive excessive radiation dose, such as heart valves, coronary arteries, cardiac conduction system, implanted defibrillator generator and lead tip, lung, spine, stomach, and bowel (Figure 4). As our SBRT delivery system (Edge Radiotherapy System, Varian Medical Systems) is not able to dynamically track target motion, movement restraints are placed on patients along with a belt to limit respiratory motion during treatment. The treatment plan is checked against a CT performed with these restraints on, and a simulated treatment is performed to ensure that therapy can be delivered as desired. Quality assurance checks are performed by the radiation physicist to ensure that the treatment dose can be adequately delivered to the target and does not exceed tolerances of collateral tissues. Thus, formulation of the treatment plan is optimized in an iterative fashion. This planning phase requires close collaboration between the electrophysiology, radiation oncology, and radiation physics teams. The planning process takes place offline, and typically requires a minimum of 3-4 days. Key members of our multidisciplinary cardiac SBRT treatment team are shown in Figure 1, and the program co-directors, Drs. Paul Zei and Raymond Mak, are shown in Figure 5.

On the day of treatment, the patient arrives to the radiotherapy suite in street clothes and is positioned on the treatment table in the same fashion as during planning CT. The treatment delivery of this system is no more than 10-15 minutes in duration. Following therapy, the patient leaves after brief observation, typically from either the radiation oncology or electrophysiology holding bays. In our institution, we have introduced standardized patient workflows and safety measures, including monitoring/interrogation of ICD function during and immediately after treatment. We closely follow patients in both the cardiac electrophysiology and device clinics as well as the radiation oncology clinic to monitor for side effects, device function, and arrhythmia control. Our clinical experience parallels that of published series.11-14 Reduction in VT burden occurs in the majority of patients in the weeks after therapy, allowing tapering of antiarrhythmic medications. This is remarkable, considering the refractory nature of arrhythmias in this patient population. The treatment is typically well tolerated; the more common side effects that can occur include fatigue, hypotension, heart failure exacerbation, pneumonitis, and pericardial effusion, which are often minor and managed conservatively. Longer-term radiation-related side effects are not yet known due to the small absolute number of patients in published reports and limited duration of follow-up.

In conclusion, SBRT is a promising new modality for cardiac ablation that has overcome major limitations in radiofrequency catheter ablation, but has also introduced new challenges. The innate freedom to design and deliver any ablation volume is paired with an obligation to improve treatment precision. Optimization of electrophysiological and anatomical imaging data integration and new methods for cardiorespiratory motion compensation would be useful in this regard. While impressive VT reduction is observed in most patients, clinical response is not uniform. Understanding the mechanism of conduction block in myocardial scar that occurs with SBRT and further optimization of dose will be critical to guide clinical practice. Furthermore, long-term patient outcomes remain unknown, and multicenter patient registries and collaborative clinical studies are needed to learn more about how best to apply this technology. Importantly, advances in SBRT for cardiac ablation have brought together disparate medical disciplines, cardiology/electrophysiology and radiation oncology, with previously little intersection. This exciting new era of collaboration may herald new advances and discoveries that could again shift our paradigm for cardiac arrhythmia management. 

Funding: Dr. Qian has received a Bushell Traveling Fellowship from the Royal Australasian College of Physicians.

Disclosures: The authors have no conflicts of interest to report regarding the content herein. Outside the submittd work, Dr. Mak reports personal fees (for scientific advisory board) from AstraZeneca and ViewRay, and personal fees (for lecture honorarium) from NewRT. Dr. Tedrow has received speaking honoraria from Abbott Medical, Boston Scientific, Medtronic, and Biosense Webster, Inc. Dr. Zei has reports receiving research support and consulting fees from CyberHeart/Varian Medical Systems, and research support and consulting fees from Biosense Webster, Inc.

References
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