左侧乳腺癌患者在放射治疗后心脏平均剂量（MHD）较高，随后增加了缺血性心脏病风险。然而，目前尚未确定心脏亚结构中最佳的剂量学预测因子。本研究对2158例接受辅助放疗的乳腺癌女性进行了回顾性研究。主要的终点指标是重大缺血事件。计算了每个划定的心脏亚结构的剂量容积参数。采用Cox回归分析了重大缺血事件的危险因素和MHD与重大缺血事件的关联。通过比较每个模型的性能指标，在多变量模型中探讨了心脏亚结构中的最佳剂量容积预测因子。在中位随访7.9年（四分位距5.6-10.8年）后，89名患者发生了重大缺血事件。左侧乳腺癌的重大缺血事件累积发生率显著高于右侧乳腺癌（P = 0.044）。总体而言，MHD每增加1Gy，重大缺血事件的风险增加6.2%（风险比1.062，95%置信区间1.01-1.12；P = 0.012）。包含接收25Gy的左心室体积（LV V25），且截断点为4%的模型在左侧乳腺癌中具有最好的适应度和区分度性能。年龄、慢性肾脏疾病和高脂血症也是显著的危险因素。在现代放疗时代存在重大缺血事件风险。LV V25≥4%似乎是最佳参数，比MHD在预测重大缺血事件方面更优。这种剂量限制有助于在乳腺癌放疗中实现更好的心脏保护，但需要进一步验证研究。© 作者2023。由牛津大学出版社代表欧洲心脏学会出版。保留所有权利。有关权限，请发送电子邮件至：journals.permissions@oup.com。

Patients with left-sided breast cancer receive a higher mean heart dose (MHD) after radiotherapy, with subsequent risk of ischaemic heart disease. However, the optimum dosimetric predictor among cardiac substructures has not yet been determined.This study retrospectively reviewed 2158 women with breast cancer receiving adjuvant radiotherapy. The primary endpoint was a major ischaemic event. The dose-volume parameters of each delineated cardiac substructure were calculated. The risk factors for major ischaemic events and the association between MHD and major ischaemic events were analysed by Cox regression. The optimum dose-volume predictors among cardiac substructures were explored in multivariable models by comparing performance metrics of each model. At a median follow-up of 7.9 years (interquartile range 5.6-10.8 years), 89 patients developed major ischaemic events. The cumulative incidence rate of major ischaemic events was significantly higher in left-sided disease (P = 0.044). Overall, MHD increased the risk of major ischaemic events by 6.2% per Gy (hazard ratio 1.062, 95% confidence interval 1.01-1.12; P = 0.012). The model containing the volume of the left ventricle receiving 25 Gy (LV V25) with the cut-point of 4% presented with the best goodness of fit and discrimination performance in left-sided breast cancer. Age, chronic kidney disease, and hyperlipidaemia were also significant risk factors.Risk of major ischaemic events exist in the era of modern radiotherapy. LV V25 ≥ 4% appeared to be the optimum parameter and was superior to MHD in predicting major ischaemic events. This dose constraint could aid in achieving better heart protection in breast cancer radiotherapy, though a further validation study is warranted.© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.