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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL129185-01
Application #
8956091
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Danthi, Narasimhan
Project Start
2015-08-15
Project End
2019-07-31
Budget Start
2015-08-15
Budget End
2016-07-31
Support Year
1
Fiscal Year
2015
Total Cost
$794,326
Indirect Cost
$337,817
Name
Beth Israel Deaconess Medical Center
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02215
Nakamori, Shiro; Alakbarli, Javid; Bellm, Steven et al. (2017) Native T1 value in the remote myocardium is independently associated with left ventricular dysfunction in patients with prior myocardial infarction. J Magn Reson Imaging 46:1073-1081
Nakamori, Shiro; Ismail, Haisam; Ngo, Long H et al. (2017) Left ventricular geometry predicts ventricular tachyarrhythmia in patients with left ventricular systolic dysfunction: a comprehensive cardiovascular magnetic resonance study. J Cardiovasc Magn Reson 19:79
Tschabrunn, Cory M; Roujol, Sébastien; Nezafat, Reza et al. (2016) A swine model of infarct-related reentrant ventricular tachycardia: Electroanatomic, magnetic resonance, and histopathological characterization. Heart Rhythm 13:262-73
Jang, Jihye; Bellm, Steven; Roujol, Sébastien et al. (2016) Comparison of spoiled gradient echo and steady-state free-precession imaging for native myocardial T1 mapping using the slice-interleaved T1 mapping (STONE) sequence. NMR Biomed 29:1486-96
Kato, Shingo; Nakamori, Shiro; Bellm, Steven et al. (2016) Myocardial Native T1 Time in Patients With Hypertrophic Cardiomyopathy. Am J Cardiol 118:1057-62
Tschabrunn, Cory M; Roujol, Sebastien; Dorman, Nicole C et al. (2016) High-Resolution Mapping of Ventricular Scar: Comparison Between Single and Multielectrode Catheters. Circ Arrhythm Electrophysiol 9:
Anter, Elad; Tschabrunn, Cory M; Buxton, Alfred E et al. (2016) High-Resolution Mapping of Postinfarction Reentrant Ventricular Tachycardia: Electrophysiological Characterization of the Circuit. Circulation 134:314-27
Kato, Shingo; Foppa, Murilo; Roujol, Sébastien et al. (2016) Left ventricular native T1 time and the risk of atrial fibrillation recurrence after pulmonary vein isolation in patients with paroxysmal atrial fibrillation. Int J Cardiol 203:848-54
Basha, Tamer A; Bellm, Steven; Roujol, Sébastien et al. (2016) Free-breathing slice-interleaved myocardial T2 mapping with slice-selective T2 magnetization preparation. Magn Reson Med 76:555-65
Kato, Shingo; Nakamori, Shiro; Roujol, Sébastien et al. (2016) Relationship between native papillary muscle T1 time and severity of functional mitral regurgitation in patients with non-ischemic dilated cardiomyopathy. J Cardiovasc Magn Reson 18:79

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