Early Right Ventricular Injury and Myocardial Metabolic Changes After Contemporary Thoracic Radiotherapy: The CONNECT study

Background Radiation-related cardiovascular disease (CVD) is a major concern for cancer survivors, yet few methods exist to detect early cardiac injury within the first year of thoracic radiotherapy. Surveillance has largely focused on the left ventricle (LV), with little attention given to the right heart which may be particularly vulnerable to radiation due to its thin wall and anterior anatomical location. We aimed to prospectively evaluate potential early multimodality biomarkers of radiation-related cardiotoxicity and examine their association with radiation dose considering the whole heart and individual chambers. Methods CONNECT was a prospective, longitudinal study enrolling patients receiving thoracic radiotherapy for lymphoma, oesophageal, or lung cancer. Participants had multimodality assessments at baseline, after anthracycline-based chemotherapy (lymphoma only), within 2 weeks after radiotherapy and after 6 months, including simultaneous cardiac 18F- fluoro-2-deoxy-D-glucose (18F-FDG) PET/MRI, serum biomarkers and 12-lead ECG. Associations between findings and radiation doses to the heart were examined. Results Twenty-four patients (72 PET/MRI scans) were analysed. Both LVEF and RVEF declined early, but only RVEF remained persistently reduced at 6 months (−5.9%, p=0.004), with ≥10% decline in 40% of patients. Abnormal 18F-FDG uptake emerged in 35% of patients at 6 months, localised to the basal myocardium. Both reduction in RVEF and abnormal uptake were correlated with cardiac doses. Relative LV global longitudinal strain was impaired (>15%) at 6 months in 35% of patients. Troponin rises were modest, transient, and not predictive of dysfunction at 6 months. T1, T2, late gadolinium enhancement and ECG showed no change. Conclusions CONNECT demonstrates that persistent early radiation-related cardiotoxicity is right sided-predominant, dose-dependent, and accompanied by left ventricular myocardial metabolic changes. These findings identify the right heart as a critical, overlooked area in radiotherapy treatment planning and cardio-oncology surveillance.