Cardiac Fibrosis and Risk Prediction in Cancer Treatment-Related Cardiotoxicity

 描述(由申请人提供)：这份指导临床科学家研究职业发展奖提案描述了明尼苏达大学心血管内科研究员切坦·谢诺伊博士的五年职业发展和培训计划。他的长期目标是成为一名独立的、以患者为导向的内科研究员，将在预防肿瘤心脏病学领域做出重大贡献。他的职业发展计划包括以下内容：受保护的研究时间、在临床研究硕士学位课程中重点讲授课程、心血管预防和先进临床研究方法方面的实践培训、与经验丰富的临床研究人员组成的多学科团队设计的高度结构化的紧密指导计划、通过设计和执行由Sheroy博士发起的前瞻性队列研究在以患者为中心的研究方面的第一手经验，以及最终成功申请独立研究资金。常见的癌症治疗，如蒽环类药物和曲妥珠单抗，会增加心脏毒性的风险，而心脏毒性是导致大量死亡的原因。 尽管目前采取了预防策略，但癌症幸存者的死亡率仍然很高。病人的识别 与癌症治疗相关的心脏毒性风险将使我们能够干预和预防心血管疾病的发病率和死亡率，并改善癌症患者的整体结局。这项拟议研究的总体目标是确定磁共振成像检测到的先前存在的心脏纤维化在预测心脏毒性药物的心脏毒性中的作用。在一项前瞻性的队列研究中，希诺伊博士将首先确定在接受蒽环类药物和/或曲妥珠单抗治疗之前，癌症患者中心脏纤维化的患病率和预测因素。下一步，他将在服用蒽环类药物和/或曲妥珠单抗24个月后，确定先前存在的心脏纤维化与心脏毒性之间的联系。最后，他将确定先前存在的心肌纤维化与使用蒽环类药物和/或曲妥珠单抗后的心肌肌钙蛋白水平之间的关系。这项研究将提供关于先前存在的心脏纤维化在心脏毒性预测中的作用的第一个系统数据，为谢诺伊博士开发预防癌症患者心血管疾病的新干预措施的长期目标奠定基础。总而言之，在明确的培训、研究和指导结构的背景下，一个全面的职业发展计划将使谢诺伊博士成为预防肿瘤心脏病学领域一名非常成功的独立内科研究员。

 DESCRIPTION (provided by applicant): This Mentored Clinical Scientist Research Career Development Award proposal describes a five-year career development and training plan for Dr. Chetan Shenoy, a cardiovascular physician investigator at the University of Minnesota. His long-term goal is to be an independent, patient-oriented physician investigator who will make significant contributions in the field of preventive onco-cardiology. His career development plan encompasses the following: protected research time, focused didactic coursework within a Masters in Clinical Research degree program, hands-on training in cardiovascular prevention and advanced clinical research methodology, a highly structured cohesive mentoring program designed with a multidisciplinary team of accomplished clinical investigators, first-hand experience in patient-oriented research through the design and execution of a prospective cohort study initiated by Dr. Shenoy, and ultimately, successful application for independent research funding. Common cancer treatments such as anthracyclines and trastuzumab are associated with an increased risk of cardiotoxicity, which is responsible for significant mortality and morbidity in cancer survivors despite current preventive strategies. Identification of patients at risk for cancer treatment-related cardiotoxicity would allow us to intervene and prevent cardiovascular morbidity and mortality and improve the overall outcomes of patients with cancer. The overall objective of the proposed research is to establish the role of pre-existing cardiac fibrosis detected by magnetic resonance imaging to predict cardiotoxicity from cardiotoxic medications. In a prospective cohort study, Dr. Shenoy will first determine the prevalence and predictors of cardiac fibrosis in cancer patients before treatment with anthracyclines and/or trastuzumab. Next, he will determine the association between pre-existing cardiac fibrosis and cardiotoxicity at 24 months after initiation of anthracyclines and/or trastuzumab. Finally, he will determine the association between pre-existing cardiac fibrosis and cardiac troponin levels after initiation of anthracyclines and/or trastuzumab. This research will provide the first systematic data on the role of pre- existing cardiac fibrosis for the prediction f cardiotoxicity, laying the foundation for Dr. Shenoy's long-term goal of developing new interventions to prevent cardiovascular disease in patients with cancer. In summary, a comprehensive career development plan in the context of a well-defined training, research and mentorship structure will allow Dr. Shenoy to emerge as a highly successful, independent physician investigator in preventive onco-cardiology.