Arrhythmogenic Toxicity in Radiotherapy: Cardiac Conduction System as an Emerging Organ at Risk

Cardiovascular disease is the most common non-oncologic cause of death in patients treated with radiotherapy in thoracic region. Radiation-induced heart disease (RIHD) includes a range of structural and functional complications, among which arrhythmogenic toxicity—conduction disorders and arrhythmias—has gained increasing attention. The cardiac conduction system is not routinely delineated as an organ at risk (OAR), nor are the surrounding structures such as the pulmonary veins, which represent a key pathophysiological site in the development of supraventricular arrhythmias. Traditional parameters like mean heart dose (MHD) may not adequately reflect regional radiosensitivity, particularly in anatomically distinct substructures located at the base of the heart, such as the sinoatrial (SA) and atrioventricular (AV) nodes. This review summarizes current evidence on the effects of radiotherapy on the cardiac conduction system and highlights emerging data on its role in arrhythmogenic toxicity. Radiation-induced arrhythmias can occur early after treatment. The heart’s heterogeneous radiosensitivity challenges the use of mean heart dose (MHD) as a predictive metric. Recent studies suggest that cardiac substructures, especially the base of the heart, may be critical regions. A shift toward substructure-specific dosimetry is needed. Recently, arrhythmogenic cardiotoxicity has attracted greater interest in lung cancer, as improvements in overall survival with immunotherapy and targeted agents have increased the relevance of long-term treatment-related toxicities, including radiation-induced arrhythmias.