Applications of Magnetic Resonance for Management of Ventricular Tachycardia

描述(由申请人提供)：我对室性心动过速(VT)患者风险分层和治疗的新方法的临床翻译感兴趣。我提出的职业发展计划包括在亨利·R·哈尔佩林博士的指导下以患者为导向的研究，以及在尼尔·R·鲍威博士的指导下的临床流行病学博士项目。Halperin博士在磁共振成像(MRI)引导电生理学的技术开发方面拥有丰富的经验。作为Halperin博士实验室的一员，在研究员期间，我使用心肌疤痕成像和表征技术来确定非缺血性心肌病患者诱导性室速的底物。自那以后，这项技术已经被其他研究小组验证，后来被证明可以识别有高猝死风险的非缺血性心肌病患者。然而，在许多其他高危患者亚群中，这种方法的益处仍然没有得到评估。即使在识别出高危患者后，目前的室速治疗也并不理想。植入式除颤器会引起痛苦的电击并降低生活质量，而导管消融与无法用透视显示室速底物而导致的失败有关。这一建议的中心假设是，通过MRI对疤痕(底物)进行可视化可以改善VT的风险分层和治疗。我的研究计划的目的是：1)检查MRI在另一个高危人群中检测VT底物的效用；2)检查预先获得的三维MRI疤痕图积分在基于底物的VT消融与标准VT消融中的疗效。重要的是，我的目标的临床重点与哈尔佩林博士对技术开发的关注是互补的，但又是截然不同的。这项技术的成功临床应用将需要全面研究各种瘢痕形态在成像上的功能电生理学相关性，并评估有效性和安全性结果。成功地将我们的技术进步转化为临床的必要性塑造了我的职业发展和研究目标，并将帮助我实现调查独立。为了正确地实现这些目标，我们将需要先进的流行病学、研究设计和生物统计学技术。为此，我在约翰霍普金斯大学彭博公共卫生学院攻读了临床流行病学博士课程。鲍威博士是流行病学和结果研究方面的专家，他将监督我的临床流行病学培训。我的另一位导师布莱恩·S·卡福博士是生物统计学和医学成像方面的专家。室性心律失常患者风险分层和治疗的新方法的翻译有可能对公众健康产生重大影响。我期待着有机会通过这项提案的资源，在临床研究中发展专业知识和调查独立性的同时，为这项重要的研究做出贡献。 公共卫生相关性： 这项建议的目的是通过以下方式促进候选人的职业发展：1)临床流行病学的教学博士项目；2)以患者为导向的针对室性心动过速的风险分层和导管消融的磁共振成像技术研究。据估计，心脏性猝死占美国总死亡率的15%。翻译室性心律失常风险分层和治疗的新方法可能会使猝死风险较高的患者得到更早的认识和更有效的治疗，并有可能对公众健康产生重大影响。(摘要结束)

DESCRIPTION (provided by applicant): I am interested in clinical translation of new methodologies for risk stratification and therapy of patients with ventricular tachycardia (VT). My proposed career development plan incorporates patient-oriented research guided by the mentorship of Dr. Henry R. Halperin, with a doctoral program in clinical epidemiology under the mentorship of Dr. Neil R. Powe. Dr. Halperin has extensive experience in technology development for magnetic resonance imaging (MRI) guided electrophysiology. As a member of Dr. Halperin's laboratory during fellowship, I used myocardial scar imaging and characterization techniques for identification of the substrate for inducible VT in patients with non-ischemic cardiomyopathy. This technique has since been validated by other groups, and was later shown to identify non-ischemic cardiomyopathy patients at high risk of sudden death. However, the benefits of such an approach remain unassessed in many other high-risk patient subsets. Even upon identification of high-risk patients, current treatments for VT are not ideal. Implantable defibrillators cause painful shocks and decrease quality of life, and catheter ablation is associated with failures deriving from the inability to visualize the VT substrate with fluoroscopy. The central hypothesis of this proposal is that scar (substrate) visualization via MRI can improve the risk stratification and therapy of VT. The aims of my research proposal are to 1) Examine the utility of MRI for detection of the VT substrate in another high risk population and 2) Examine the efficacy of pre-acquired three-dimensional MRI scar map integration for substrate based VT ablation versus standard VT ablation. Importantly, the clinical focus of my aims is complementary, but distinct, from Dr. Halperin's focus on technology development. Successful clinical translation of such technology will require comprehensive study of the functional electrophysiology correlates of various scar morphologies on imaging, and assessment of effectiveness and safety outcomes. The necessity of successful clinical translation of our technologic advances has shaped my career development and research aims and will help me achieve investigative independence. To properly address these aims we will require sophisticated epidemiologic, study design, and biostatistical techniques. To this end, I have enrolled in the doctoral clinical epidemiology program at the Johns Hopkins Bloomberg School of Public Health. Dr. Powe, an expert in epidemiology and outcomes research, will oversee my training in clinical epidemiology. My other mentor, Dr. Brian S. Caffo is an expert in biostatistics and medical imaging. Translation of new methodologies for risk stratification and treatment of patients with ventricular arrhythmia has the potential to impact public health significantly. I look forward to the opportunity to contribute to this important research while developing expertise and investigative independence in clinical research, through the resources of this proposal. PUBLIC HEALTH RELEVANCE: The aim of this proposal is to enhance the career development of the candidate through: 1) a didactic doctoral program in clinical epidemiology and 2) patient oriented research in magnetic resonance imaging techniques for risk stratification and catheter ablation of ventricular tachycardia. It is estimated that sudden cardiac death accounts for up to 15 percent of the total mortality in the United States. Translation of new methodologies for risk stratification and treatment of ventricular arrhythmia may allow earlier recognition and more effective treatment for patients at high risk of sudden death, and has the potential to impact public health significantly. (End of Abstract)