title: Dose-escalation study for cardiac radiosurgery in a porcine model.
abstract: OBJECTIVE
  To perform a proof-of-principle dose-escalation study to radiosurgically induce scarring in cardiac muscle tissue to block veno-atrial electrical connections at the pulmonary vein antrum, similar to catheter ablation.
  
  
  METHODS
  Nine mini-pigs underwent pretreatment magnetic resonance imaging (MRI) evaluation of heart function and electrophysiology assessment by catheter measurements in the right superior pulmonary vein (RSPV). Immediately after examination, radiosurgery with randomized single-fraction doses of 0 and 17.5-35 Gy in 2.5-Gy steps were delivered to the RSPV antrum (target volume 5-8 cm(3)). MRI and electrophysiology were repeated 6 months after therapy, followed by histopathologic examination.
  
  
  RESULTS
  Transmural scarring of cardiac muscle tissue was noted with doses ≥32.5 Gy. However, complete circumferential scarring of the RSPV was not achieved. Logistic regressions showed that extent and intensity of fibrosis significantly increased with dose. The 50% effective dose for intense fibrosis was 31.3 Gy (odds ratio 2.47/Gy, P<.01). Heart function was not affected, as verified by MRI and electrocardiogram evaluation. Adjacent critical structures were not damaged, as verified by pathology, demonstrating the short-term safety of small-volume cardiac radiosurgery with doses up to 35 Gy.
  
  
  CONCLUSIONS
  Radiosurgery with doses >32.5 Gy in the healthy pig heart can induce circumscribed scars at the RSPV antrum noninvasively, mimicking the effect of catheter ablation. In our study we established a significant dose-response relationship for cardiac radiosurgery. The long-term effects and toxicity of such high radiation doses need further investigation in the pursuit of cardiac radiosurgery for noninvasive treatment of atrial fibrillation.
authors.affiliation: Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany; CyberKnife Center Northern Germany, Guestrow, Germany. Electronic address: oliver.blanck@uksh.de.
authors.forename: Oliver
authors.initials: O
authors.lastname: Blanck
authors.affiliation: Medical Department II, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Bode
authors.affiliation: Institute of Pathology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Gebhard
authors.affiliation: Department of Radiology and Nuclear Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hunold
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brandt
authors.affiliation: Institute for Robotics and Cognitive Systems, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Bruder
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Grossherr
authors.affiliation: Institute of Medical Biometry and Statistics, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Vonthein
authors.affiliation: Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.affiliation: Department of Radiation Oncology, University of Luebeck and University Medical Center Schleswig-Holstein, Campus Luebeck, Germany; University Copenhagen, Denmark.
authors.forename: Juergen
authors.initials: J
authors.lastname: Dunst
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology / Q000528:radiation effects*; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D009206:Myocardium / Q000473:pathology; D058958:Organs at Risk / Q000528:radiation effects; D011667:Pulmonary Veins / Q000528:radiation effects*; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods*; D011879:Radiotherapy Dosage; D013552:Swine