Radiation-induced cardiovascular disease affects 10-30% of long-term survivors, with cardiac fibrosis following radiation-induced aortitis emerging as a key driver of morbidity.
Cardiac fibrosis following radiation-induced aortitis is an emerging clinicopathologic entity requiring lifelong surveillance and further research into targeted antifibrotic therapies.
Dear Editor, Cardiac fibrosis in post-radiation aortitis is an arising intricacy of thoracic radiotherapy, representing the overlap of vascular inflammation and myocardial remodeling. This entity is clinically essential because radiation-induced cardiovascular disease affects 10–30% of long-term survivors, often manifesting decades after treatment, with fibrosis serving as a key driver of morbidity1,2. Recognition is essential, as fibrosis is progressive yet potentially modifiable with targeted therapies. Radiotherapy is typically related to coronary artery disease, valve damage, and pericardial fibrosis. A recent research suggests that radiation-induced aortitis can progress to fibrotic remodeling of the aorta wall, including extension into the myocardium. Endothelial damage, microvascular ischemia, and chronic inflammation contribute to a profibrotic environment, with TGF-β playing a key role. TGF-β activates myofibroblasts and deposits extracellular matrix, whereas CTGF promotes fibrosis downstream. Emerging evidence suggests MicroRNAs like miR-21 further influence this signaling network3–5. Radiation-induced vasculopathy involving large vessels has been documented, including rare cases of radiation-induced aortitis detected on cross-sectional imaging after chemoradiation for cervical cancer6. Myocardial fibrotic remodeling and cardiomyopathy have also been reported as late sequelae of thoracic irradiation, confirmed with cardiac magnetic resonance and histopathology7. Longitudinal imaging studies show progressive diffuse myocardial fibrosis following radiotherapy for breast cancer8. Radiation-related fibrosis is rarely seen alone; it is usually coupled with valvular disease, restrictive cardiomyopathy, coronary atherosclerosis, and pulmonary fibrosis3,4. Thyroid disease is very common in thoracic irradiation survivors, exacerbating late morbidity. Therapeutic strategies are still in the experimental stage. Preclinical efficacy has been shown for the anti-TGF-β drugs fresolimumab and pamrevlumab, whereas nintedanib, a tyrosine kinase inhibitor that is approved for pulmonary fibrosis, may have cardiac uses9. Although the long-term effects are not always constant, pentoxifylline and vitamin E have demonstrated benefits in reducing radiation fibrosis10. Lifelong surveillance with cardiac magnetic resonance imaging, echocardiography, and biomarkers (TGF-β, CTGF, and miR-21) is advised for early diagnosis due to the decades-long latency. This article aligns with the TITAN Guidelines on the need for transparency in AI use in healthcare11. Cardiac fibrosis developing after radiation-induced aortitis should be recognized as a separate clinical condition that connects vascular injury with myocardial damage. Detecting it early, using biomarker-based surveillance, and testing antifibrotic treatments may help improve long-term outcomes in cancer survivors. Current evidence is largely observational and extrapolated, highlighting the need for systematic characterization.
Rehman et al. (Tue,) conducted a letter in Cardiac fibrosis following radiation-induced aortitis. Radiation-induced cardiovascular disease affects 10-30% of long-term survivors, with cardiac fibrosis following radiation-induced aortitis emerging as a key driver of morbidity.