2010 — 2014 |
Nazarian, Saman |
K23Activity Code Description: To provide support for the career development of investigators who have made a commitment of focus their research endeavors on patient-oriented research. This mechanism provides support for a 3 year minimum up to 5 year period of supervised study and research for clinically trained professionals who have the potential to develop into productive, clinical investigators. |
Applications of Magnetic Resonance For Management of Ventricular Tachycardia @ Johns Hopkins University
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)
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1 |
2013 — 2016 |
Nazarian, Saman |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Ancillary Study of Substrate and Intervention Mechanisms For Malignant Arrhythmia @ Johns Hopkins University
DESCRIPTION (provided by applicant): Life-threatening ventricular tachycardia (VT) remains a major complication of myocardial infarction. The VT substrate is diseased myocardium that slows local conduction sufficiently to perpetuate circuit reentry. This proposal aims to enhance our understanding of the anatomic details of the VT substrate and its effects upon patient response to antiarrhythmic drug therapy and catheter ablation, an alternative mode of therapy that aims to destroy the VT substrate. Currently, ablation is performed by use of local, point-by-point acquired, intra- cardiac electrograms, which serve as surrogates for each patient's unique VT substrate. This strategy is limited by low sampling density and lack of specificity. Direct evaluation of the anatomic VT substrate has recently become feasible with imaging techniques such as computed tomography (CT). We propose a time-sensitive ancillary study to the Ventricular Tachycardia Ablation vs. Enhanced Drug Therapy In Structural Heart Disease (VANISH) and the Early Ablation Therapy for the Treatment of Ischemic Ventricular Tachycardia in Patients with Implantable Cardioverter Defibrillators (ASPIRE) multicenter randomized clinical trials. We will acquire resting myocardial CT perfusion and delayed contrast-enhanced CT infarct imaging in 200 VANISH and ASPIRE participants prior to randomization, and at 1-year follow-up. The data will be used to a) define anatomic features that predict the optimal mode of VT therapy thereby allowing proper selection of ablation versus antiarrhythmic drugs, b) define the anatomic details of slow conduction VT substrates, c) determine the substrate changes necessary for VT suppression, and d) characterize the resultant cardiac remodeling from ablation versus drug therapy. We have assembled a team of experts in CT image acquisition and analysis, epidemiology, biostatistics, and VT management. The findings of this study will have wide applicability to optimization of management strategies for patients with post-infarct VT.
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1 |
2018 — 2021 |
Nazarian, Saman Trayanova, Natalia A. (co-PI) [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Implications of Intra-Myocardial Fat Deposition Upon Propensity For Maligt Arrhythmia @ University of Pennsylvania
Life-threatening ventricular tachycardia (VT) remains a major complication of myocardial infarction. Catheter ablation aims to destroy the VT substrate, diseased myocardium that slows local conduction sufficiently to perpetuate circuit reentry. The current understanding of the VT substrate revolves around the interaction of surviving strands of viable myocardium primarily at the periphery of infarct scar. Our preliminary data, however, suggests that critical VT circuit sites are viable myocardial strands that reside in the scar core, and are often surrounded by intra-myocardial fat deposition. Intra-myocardial fat is not a simple bystander; it is metabolically active and vascular, an effective insulator of conductive fibers, and modulates local conduction properties. This proposal will investigate the mechanistic consequence of intra-myocardial fat deposition upon impulse conduction and the propensity to sustain VT in adults with prior myocardial infarction. We propose to use MRI and CT images of patients with post-infarct VT to 1) to define the prevalence and distribution of myocardial fat deposition in patients with prior infarction and VT, 2) to characterize the conduction and repolarization properties of viable channels within scar based upon proximity to myocardial fat, 3) to examine the association of VT circuit sites with proximity to myocardial fat, and 4) to dissect the contribution of myocardial fat to VT events using patient-specific models, and to evaluate the diagnostic performance of model-predicted optimal ablation sites with and without inclusion of myocardial fat. Our group has extensive experience with MRI safety and image optimization in defibrillator recipients. Additionally, we have assembled a team of experts in image acquisition and analysis, epidemiology, biostatistics, simulations, and VT management. The findings of this study will have wide applicability to our mechanistic understanding and management of post-infarct VT.
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0.946 |