Unveiling the distinctive impact of radiation on cardiac ventricular regions and the right atrium using multi-omics approaches

Radiotherapy (RT)-induced cardiac toxicity (RICT) is widely acknowledged as a major side effect of RT, which encompasses cardiovascular complications. Despite advances in understanding the underlying biological mechanisms, a complete characterisation of the molecular changes induced by RT in the different cardiac regions is still absent. Here, a multi-omics approach was adopted to longitudinally characterise the unique response to radiation in the heart base (including ventricular base and right atrium), or the apex of the heart. The ventricular base showed a cardiomyopathy phenotype, with pronounced molecular perturbations in metabolism and electrical conduction, while changes in tissue structure were predominant in ventricular apex. We then identified a molecular signature showing that base radiation-mediated remodelling leads to a higher incidence of atrial fibrillation (AF). This study represents a comprehensive characterisation of differential spatiotemporal radiation effects in the heart and highlights several biological pathways that are potentially clinically actionable for cardiac radioprotection and monitoring.