Radiation induces diffuse extracellular remodeling of healthy myocardium in a dose- and time-dependent manner without...

Although early studies of cardiac stereotactic body radiotherapy (cSBRT) show promise as a therapy to treat drug-refractory ventricular tachycardia, there remain knowledge gaps in its application, including the ideal doses to apply, which radiation source to use, which substrates to target, and the structural and electrophysiological effects seen after cSBRT.

Here, we examine doses up to 50 Gy to assess lesion formation by longitudinally following healthy myocardium after photon radiation using cardiac magnetic resonance (CMR) imaging and correlating those findings with histologic analysis.

Eight healthy canines underwent stereotactic photon beam cSBRT targeting healthy cardiac tissue. Serial CMR imaging assessed structural changes over time, imaging with late gadolinium enhancement, pre- and postcontrast T1, and precontrast T2 mapping. CMR images were registered to dosing plans, and left ventricular regions in 10 Gy increments from 0 to 50 Gy were identified for analysis. Histologic analysis was conducted postmortem to quantify fibrosis.

Scar-like late gadolinium enhancement intensity was observed only in regions receiving 40 to 50 Gy within 3 months after cSBRT but was confined to small relative volumes (<4% of target volume). T1 and extracellular volume values increased in a dose- and time-dependent manner, reaching physiological levels associated with diffuse fibrosis primarily with high doses yet present in low-dose regions. Histologic examination revealed a 102.7% relative increase (+0.38% absolute increase) in diffuse fibrosis in targeted regions compared with nonirradiated controls and a 34.41% relative increase (+0.19% absolute increase) in diffuse fibrosis in nontargeted regions at chronic time points (>90 days).

Photon cSBRT induces structural remodeling in healthy ventricular myocardium, primarily manifesting as diffuse remodeling that progressively increases with the radiation dose and the time interval after radiation without large areas of dense scar formation. These findings provide insight into the long-term effects of cSBRT, showing that healthy myocardium is unlikely to form large scar regions within 3 months and that diffuse remodeling should be further considered as a long-term effect of cSBRT.