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Henry R. Halperin博士的指导下进行以患者为导向的研究，在Neil R. Powe博士的指导下进行临床流行病学博士课程。Halperin博士在磁共振成像（MRI）引导电生理的技术开发方面拥有丰富的经验。作为Halperin博士实验室的成员，我使用心肌疤痕成像和表征技术来识别非缺血性心肌病患者诱导VT的底物。这项技术已被其他小组验证，后来被证明可以识别猝死高风险的非缺血性心肌病患者。然而，这种方法的益处在许多其他高危患者亚群中仍未得到评估。即使在确定高危患者后，目前对室速的治疗也不理想。植入式除颤器会引起痛苦的休克并降低生活质量，而导管消融与无法通过透视观察VT底物而导致的失败有关。本提案的中心假设是，通过MRI显示疤痕（基底）可以改善VT的风险分层和治疗。我的研究提案的目的是：1)检查MRI在另一个高风险人群中检测VT基底的实用性；2)检查预先获得的三维MRI疤痕图谱整合对基于基底的VT消融与标准VT消融的有效性。重要的是，我的临床目标与Halperin博士对技术开发的关注是互补的，但又截然不同。这种技术的成功临床转化需要对各种疤痕形态学成像的功能电生理学相关性进行全面研究，并评估其有效性和安全性。我们的技术进步的成功临床转化的必要性塑造了我的职业发展和研究目标，并将帮助我实现研究独立性。为了正确地实现这些目标，我们将需要复杂的流行病学、研究设计和生物统计学技术。为此，我报名参加了约翰霍普金斯大学彭博公共卫生学院的临床流行病学博士项目。鲍尔博士是流行病学和结果研究方面的专家，他将监督我在临床流行病学方面的培训。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。翻译室性心律失常患者风险分层和治疗的新方法有可能对公众健康产生重大影响。我期待着有机会为这项重要的研究做出贡献，同时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。

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)