Feasibility study on stereotactic radiotherapy for total pulmonary vein isolation in a canine model

Abstract

We tested the feasibility of pulmonary vein (PV) and left atrial (LA) posterior wall isolation using non-invasive stereotactic ablative body radiotherapy (SABR) and investigated pathological changes in irradiated lesions in a canine model. Seven male Mongrel dogs received single-fraction 33 Gy SABR. We designed the en-bloc circular target of total PVs and LA posterior wall to avoid the esophagus. The circular box lesion included the LA roof and ridge, low posterior wall, and posterior interatrial septum. At 6 weeks or 4 months post-SABR, electrical isolation of the SABR lesion was confirmed using LA posterior wall pacing, and histopathological review was performed. Electrical isolation of all PVs and the LA posterior wall was achieved in three of five dogs in the 4-month group. There was one target failure and one sudden death at 15 weeks. Although two dogs in the 6-week group failed to achieve electrical lesion isolation, the irradiated atrial myocardium showed diffuse hemorrhage with inflammatory cell infiltration. In successfully isolated 4-month model dogs, we observed transmural fibrotic scarring with extensive fibrosis on irradiated atrial tissue. The findings suggest that this novel circular box-design radiotherapy technique using SABR could be applied to humans after further studies are conducted to confirm safety.

Stereotactic Radiotherapy Ablation and Atrial Fibrillation: Technical Issues and Clinical Expectations Derived From a Systematic Review

“…The first study on the in vivo cardio ablation for AF was performed in 2010 by Sharma et al ( 41 ). Overall, preclinical studies were conducted on healthy animals subjects, with 26 mini-pigs; in only 3 studies also canines were considered ( 42 – 44 ), for a total number of 27 cases ( Table 1 ). Average or median doses could not be calculated for preclinical works due to a lack of information in some of the included studies.…”

“…For treatments delivered by CK, fiducials (both gold seeds and catheter tips) were necessary to evaluate target motion. A CLA was used in 3 cases ( 44 – 46 ). In almost all the articles, both cardiac and respiratory motions were considered, except for Chang et al ( 44 ) who acquired four-dimensional computed tomography (4DCT) only in case of the large respiratory amplitude of the animal, a single phase scan was considered and performed in others.…”

“…A CLA was used in 3 cases ( 44 – 46 ). In almost all the articles, both cardiac and respiratory motions were considered, except for Chang et al ( 44 ) who acquired four-dimensional computed tomography (4DCT) only in case of the large respiratory amplitude of the animal, a single phase scan was considered and performed in others. The same authors tried to use masks in 2 dogs and had to change immobilization systems to a vacuum cushion during simulation CT.…”

“…Efficacy of radiotherapy ablation was generally confirmed at doses up to about 25–30 Gy; side effects (i.e., bronchial-mediastinal fistula with pneumonia and sepsis) were observed in one mini-swine 1 month after irradiation when the delivered dose exceeded 37.5 Gy ( 46 ). Moreover, one animal experienced a myocardial infection following fiducial marker placement ( 43 ) and another pericardial effusion ( 44 ). Mild side effects were mitral valve regurgitation after the procedure in one case ( 42 ), one mild reduction of ejection fraction ( 43 ), and electrocardiographic, self-limiting abnormalities on T wave after anesthesia (4 animals) ( 43 ).…”

“…This choice can be explained by their relative growth stability and the consequent capability of weight maintenance during follow-up. Three of the analyzed studies also considered a canine model ( 42 – 44 ). However, regardless of the chosen animal models ( 68 ), transferability concerns for clinical applications in humans exist.…”