Sudden cardiac death (SCD) associated with scar-related ventricular tachycardia and fibrillation (VT/VF) is one of the main causes of death in the United States. Several randomized, multi-center trials have demonstrated a survival benefit with implantable cardioverter-defibrillator (ICDs), but with a societal expenditure of $2-4 billion. Unfortunately, a majority (=90%) of patients receiving an ICD for primary prevention do not benefit from the ICD, yet are exposed to the associated costs and morbidity. Therefore, imaging biomarkers that identify patients who will most benefit from ICD implantation will have substantial clinical and economic impact. The overall objective of this proposal is to identify cardiac MR (CMR) biomarkers of the substrate of ventricular arrhythmia in a swine model of VT as well as in patients with prior myocardial infarction (MI) and thereby identify the CMR biomarkers that can discriminate the patients who will most benefit from an ICD implantation for primary prevention of SCD. CMR allows for the characterization of myocardial infarcts using late gadolinium enhancement (LGE) and interstitial diffuse fibrosis using myocardial T1 mapping. Heterogeneous scar area of LGE, i.e. areas with intermediate LGE signal level surrounding or within dense scar, have been suggested to be the CMR biomarker for the arrhythmogenic scar. However, reproducible measurement of this heterogeneous area is challenging. Our preliminary data in swine model of VT as well as recent data in VT patients undergoing invasive left ventricular (LV) voltage mapping suggest that the conducting channels identified from high-resolution 3D LGE are surrogates of arrhythmogenic scar, thereby suggesting that 3D LGE could be used to identify arrhythmogenic scar. Furthermore, our recent ability in imaging the interstitial diffuse fibrosis could fundamentally change our ability in assessing future SCD risk. We recently developed a multi-slice myocardial T1 mapping sequence that allows accurate, reproducible and precise quantification of T1 mapping over the entire ventricle. Successful completion of this proposal will improve our understanding of VT substrate by characterizing the relationship between what we measure in CMR (anatomical) vs. invasive electrograms (electrical) in both swine model and patient; Furthermore it will provide additional imaging-based risk factors to improve current risk stratification scheme to identify patients who most benefit from the primary prevention ICD.
Sudden cardiac death (SCD) associated with scar-related ventricular tachycardia and fibrillation (VT/VF) is one of the main causes of death in the United States. Several randomized, multi-center trials have demonstrated a survival benefit with implantable cardioverter-defibrillator (ICDs), but with a societal expenditure of $2-4 billion. Unfortunately, a majority (=90%) of patients receiving an ICD for primary prevention do not benefit from the ICD, yet are exposed to the associated costs and morbidity. Therefore, imaging biomarkers that identify patients who will most benefit from ICD implantation will have substantial clinical and economic impact. The overall objective of this proposal is to identify cardiac MR (CMR) biomarkers of the substrate of ventricular arrhythmia in a swine model of VT as well as in patients with prior myocardial infarction (MI) and thereby identify the CMR biomarkers that can discriminate the patients who will most benefit from an ICD implantation for primary prevention of SCD.
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