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.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZHL1-CSR-R (O1))
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Scott, Jane
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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Zghaib, Tarek; Shahid, Adeel; Pozzessere, Chiara et al. (2018) Validation of contrast-enhanced time-resolved magnetic resonance angiography in pre-ablation planning in patients with atrial fibrillation: comparison with traditional technique. Int J Cardiovasc Imaging 34:1451-1458
Xie, Shuanglun; Desjardins, Benoit; Kubala, Maciej et al. (2018) Association of regional epicardial right ventricular electrogram voltage amplitude and late gadolinium enhancement distribution on cardiac magnetic resonance in patients with arrhythmogenic right ventricular cardiomyopathy: Implications for ventricular ta Heart Rhythm 15:987-993
Zghaib, Tarek; Malayeri, Ashkan A; Ipek, Esra G et al. (2018) Visualization of acute edema in the left atrial myocardium after radiofrequency ablation: Application of a novel high-resolution 3-dimensional magnetic resonance imaging sequence. Heart Rhythm 15:1189-1197
Zghaib, Tarek; Keramati, Ali; Chrispin, Jonathan et al. (2018) Multimodal Examination of Atrial Fibrillation Substrate: Correlation of Left Atrial Bipolar Voltage Using Multi-Electrode Fast Automated Mapping, Point-by-Point Mapping, and Magnetic Resonance Image Intensity Ratio. JACC Clin Electrophysiol 4:59-68
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Nazarian, Saman; Hansford, Rozann; Rahsepar, Amir A et al. (2017) Safety of Magnetic Resonance Imaging in Patients with Cardiac Devices. N Engl J Med 377:2555-2564
Gucuk Ipek, Esra; Marine, Joseph E; Habibi, Mohammadali et al. (2016) Association of left atrial function with incident atypical atrial flutter after atrial fibrillation ablation. Heart Rhythm 13:391-8
Chrispin, Jonathan; Gucuk Ipek, Esra; Zahid, Sohail et al. (2016) Lack of regional association between atrial late gadolinium enhancement on cardiac magnetic resonance and atrial fibrillation rotors. Heart Rhythm 13:654-60
Fukumoto, Kotaro; Habibi, Mohammadali; Ipek, Esra Gucuk et al. (2016) Association of Left Atrial Local Conduction Velocity With Late Gadolinium Enhancement on Cardiac Magnetic Resonance in Patients With Atrial Fibrillation. Circ Arrhythm Electrophysiol 9:e002897

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