Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia

Abstract

Background: Recent advances have enabled noninvasive mapping of cardiac arrhythmias with electrocardiographic imaging and noninvasive delivery of precise ablative radiation with stereotactic body radiation therapy (SBRT). We combined these techniques to perform catheter-free, electrophysiology-guided, noninvasive cardiac radioablation for ventricular tachycardia.

Methods: We targeted arrhythmogenic scar regions by combining anatomical imaging with noninvasive electrocardiographic imaging during ventricular tachycardia that was induced by means of an implantable cardioverter-defibrillator (ICD). SBRT simulation, planning, and treatments were performed with the use of standard techniques. Patients were treated with a single fraction of 25 Gy while awake. Efficacy was assessed by counting episodes of ventricular tachycardia, as recorded by ICDs. Safety was assessed by means of serial cardiac and thoracic imaging.

Results: From April through November 2015, five patients with high-risk, refractory ventricular tachycardia underwent treatment. The mean noninvasive ablation time was 14 minutes (range, 11 to 18). During the 3 months before treatment, the patients had a combined history of 6577 episodes of ventricular tachycardia. During a 6-week postablation "blanking period" (when arrhythmias may occur owing to postablation inflammation), there were 680 episodes of ventricular tachycardia. After the 6-week blanking period, there were 4 episodes of ventricular tachycardia over the next 46 patient-months, for a reduction from baseline of 99.9%. A reduction in episodes of ventricular tachycardia occurred in all five patients. The mean left ventricular ejection fraction did not decrease with treatment. At 3 months, adjacent lung showed opacities consistent with mild inflammatory changes, which had resolved by 1 year.

Conclusions: In five patients with refractory ventricular tachycardia, noninvasive treatment with electrophysiology-guided cardiac radioablation markedly reduced the burden of ventricular tachycardia. (Funded by Barnes-Jewish Hospital Foundation and others.).

Figures

Figure 1. Workflow for Electrophysiology-Guided, Noninvasive Cardiac Radioablation

Patients undergo noninvasive visualization of the ventricular scar by means of MRI, CT, single-photon emission CT (SPECT), or a combination of methods, according to clinical routine. The zone of scarring is indicated by arrows on MRI and by blue regions on SPECT, including the base, inferior wall, and apex. Noninvasive electrophysiologic (EP) mapping is performed with electrocardiographic imaging (ECGI) of induced ventricular tachycardia (VT) with programed stimulation from the indwelling implantable cardioverter–defibrillator. The color scale shows the range of activation times of each area of the ventricular wall (isochrones), ranging from 10 msec (red) to 190 msec (deep blue) from the onset of VT activation. The electrophysiologist develops an ablation volume by targeting the full thickness of the ventricular wall harboring the first 10 msec of VT activation (the “exit site”) and the colocalized ventricular scar. (Details regarding scar imaging, EP mapping, and image fusion to develop the ablation volume are provided in the Supplementary Appendix.) The target volume is shown in light blue in the figure panel showing the arrhythmogenic scar substrate. This volume is transferred by the radiation oncologist onto a respiratory-correlated, four-dimensional CT scan, which allows an assessment of the total cardiac and pulmonary motion. In this example, a dose of 25 Gy in a single fraction is prescribed for delivery to the enhanced treatment volume, with a goal of achieving maximal coverage inside the volume while avoiding exposure to the surrounding organs at risk. The target volume is indicated in light blue in the figure panel showing the treatment plan; red and yellow boundaries indicate the distribution of zones projected to receive 2750 cGy and 2375 cGy of radiation, respectively; the lung is outlined in orange, and the yellow boundary behind the heart is the esophagus. If all plans pass standard internal physics quality assurance on a calibrated phantom, the patient is immobilized with the use of a vacuum-assisted device, and stereotactic radioablation is performed by means of an image-guided, radiotherapy-equipped linear accelerator that uses a cone-beam CT to align the radiotherapy treatment beams with the target volume. The dark blue boundary indicates the target, which includes the total cardiac and pulmonary motion. The light blue boundary indicates the target with an additional expansion to account for motion, setup uncertainty, and delivery uncertainty. Treatment is then delivered with the use of the radiotherapy delivery system. LAD denotes left anterior descending.

Figure 2. Assessment of Treatment Efficacy

Panel A shows the total number of episodes of ventricular tachycardia (VT), including appropriate shocks from an implantable cardioverter–defibrillator (ICD), appropriate ICD antitachycardia pacing, and sustained untreated VT, in each of the five study patients, for 3 consecutive months before treatment and continuing for 12 months after treatment. In Patients 4 and 5, the numbers of VT episodes were markedly greater than in Patients 1, 2, and 3; therefore, the numbers that are shown for Patients 4 and 5 have been divided by 30 to allow comparisons on the same scale. Also shown are the total numbers of ICD shocks (Panel B) and numbers of episodes of antitachycardia pacing (Panel C) for all five patients during the same time frame. Six weeks after treatment, all four surviving patients were able to discontinue their antiarrhythmic medications, although Patient 3 restarted amiodarone 9 months after treatment of the first episode of antitachycardia pacing. Four weeks after treatment, Patient 4 underwent invasive catheter ablation because of incomplete cessation of ventricular tachycardia, with no further episodes by 12 months.

Figure 3. Assessment of Adverse Effects

Panel A shows serial evaluation of the left ventricular ejection fraction after treatment in each of the study patients, as assessed on echocardiography. The mean value increased by 6 percentage points (range, −2 to 22). Panel B shows serial thoracic CT scans after treatment in Patient 1. The treatment area is shown in blue. At 3 months, there were adjacent local inflammatory changes in the lung parenchyma, effects that had nearly resolved at 12 months. A similar pattern was observed in the other study patients.

Figure 4. Histologic Assessment of Targeted Myocardium on Autopsy

Panel A shows prominent small-vessel ectasis at the interface of dense fibrosis (upper right) and viable myocardium (lower left) in postmortem cardiac samples obtained from Patient 5, who had a fatal stroke 3 weeks after treatment. There is no acute myocardial inflammation or acute cellular necrosis. Panel B from the transition region shows occasional rectangular “boxcar” nuclei (white arrow) and hypertrophic cardiomyocytes, which are observed in chronic stages of heart failure. Endothelial cells are normal in appearance (black arrows), showing long, thin, nonreactive nuclei. (Hematoxylin and eosin staining was used in both panels.)