Principal Investigator/Program Director (Last, first, middle): Kwong, Raymond RESEARCH &RELATED Other Project Information 1. * Are Human Subjects Involved? l Yes m No 1.a. If YES to Human Subjects Is the IRB review Pending? l Yes m No IRB Approval Date: Exemption Number: 1 2 3 4 5 6 Human Subject Assurance Number 00000484 2. * Are Vertebrate Animals Used? m Yes l No 2.a. If YES to Vertebrate Animals Is the IACUC review Pending? m Yes m No IACUC Approval Date: Animal Welfare Assurance Number 3. * Is proprietary/privileged information m Yes l No included in the application? 4.a.* Does this project have an actual or potential impact on m Yes l No the environment? 4.b. If yes, please explain: 4.c. If this project has an actual or potential impact on the environment, has an exemption been authorized or an environmental assessment (EA) or environmental impact statement (EIS) been performed? m Yes m No 4.d. If yes, please explain: 5.a.* Does this project involve activities outside the U.S. or m Yes l No partnership with International Collaborators? 5.b. If yes, identify countries: 5.c. Optional Explanation: 6. * Project Summary/Abstract 7281-ProjectSummary.pdf Mime Type: application/pdf 7. * Project Narrative 2576-ProjectNarrative.pdf Mime Type: application/pdf 8. Bibliography &References Cited 7413-Bibliography.pdf Mime Type: application/pdf 9. Facilities &Other Resources 708-Facilities.pdf Mime Type: application/pdf 10. Equipment 7422-Equipment.pdf Mime Type: application/pdf 11. Other Attachments 3210-Yan_Circulation2006.pdf Mime Type: application/pdf 11. Other Attachments 3122-CIRCULATIONAHA.105.570648v1M.pidmf e Type: application/pdf Tracking Number: Other Information Page 5 OMB Number: 4040-0001 Expiration Date: 04/30/2008 Principal Investigator/Program Director (Last, first, middle): Kwong, Raymond Project Summary/Abstract The incidence of sudden cardiac death (SCD) after myocardial infarction (MI) has remained unchanged and is most significant in the first year after MI. The marked cellular anisotropy observed in the peri-infarct zone has reported to be a potential cause of ventricular arrhythmias. Cardiac magnetic resonance imaging (CMR) can characterize myocardial tissue changes and ventricular function after MI. Recently, our group demonstrated the clinical feasibility of quantifying the extent of the peri-infarct zone using contrast-enhanced CMR (PIZCMR) and also reported its strong prognostic association with post-MI all-cause mortality.(3) In a study of 144 patients with MI, we used a novel automated technique to quantify the late-enhancing region into the core and peri-infarct (PIZCMR) regions based on signal-intensity threshold (>3SDs and 2 to 3 SDs above remote normal myocardium, respectively). PIZCMR was quantified in absolute mass (MDEperiphery) and as a percentage of the total enhancing region (%MDEperiphery). We found that %MDEperiphery was a powerful predictor of all-cause mortality incremental to patient age and left ventricular ejection fraction (LVEF). With recent advances in digital signal processing, microvolt T-wave alternans (MTWA) in detecting unstable electrophysiological substrate that exposes post-MI patients to SCD. On the therapeutic side, strong experimental evidence of membrane stabilization effects of omega-3 polyunsaturated fatty acids (?-3 FA) against malignant arrhythmias has been substantiated by a remarkable reduction of SCD in patients with coronary artery disease in large-scale randomized clinical trials. These published findings provide the impetus for the present proposal to elucidate the pathogenic basis underlying the observed prognostic association of PIZCMR and post-MI mortality. The central hypothesis of this proposal is that PIZCMR contains the structural and electrical substrate essential for the generation of reentrant ventricular tachycardia, and that its healing can be promoted by ?-3 FA, translating to a reduced risk of SCD and/or significant ventricular arrhythmic events requiring defibrillation. Accordingly, we plan to randomized 414 patients with acute MI to supplementation with either ?-3 FA (4 gm/day for 9 months) or placebo is designed to test the hypotheses that 1) Direct myocardial quantitation of PIZCMR provides incremental prognostic association, beyond LVEF and MTWA, with MACE;2) Oral supplementation with ?-3 FA can beneficially modify the prognostic association of the PIZCMR with MACE;3) Patients who suffered an acute MI and have a large PIZCMR, exhibit concomitant electrical heterogeneity by MTWA;and 4) Oral ?-3 FA supplementation to patients who suffered an acute MI, reduces the myocardial extent of PIZCMR and normalizes MTWA, compared to the placebo control group. Project Description Page 6 Raymond Y. Kwong, MD 2/5/07 2:09 AM 30 Page of 38

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL091157-02S1
Application #
7837521
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Mascette, Alice
Project Start
2009-07-15
Project End
2012-06-30
Budget Start
2009-07-15
Budget End
2012-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$384,867
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Vita, Tomas; Gräni, Christoph; Abbasi, Siddique A et al. (2018) Comparing CMR Mapping Methods and Myocardial Patterns Toward Heart Failure Outcomes in Nonischemic Dilated Cardiomyopathy. JACC Cardiovasc Imaging :
Heydari, Bobak; Harris, William S; Kwong, Raymond Y (2017) Response by Heydari et al to Letter Regarding Article, ""Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial"". Circulation 135:e13-e14
Heydari, Bobak; Abdullah, Shuaib; Pottala, James V et al. (2016) Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial. Circulation 134:378-91
Heydari, Bobak; Juan, Yu-Hsiang; Liu, Hui et al. (2016) Stress Perfusion Cardiac Magnetic Resonance Imaging Effectively Risk Stratifies Diabetic Patients With Suspected Myocardial Ischemia. Circ Cardiovasc Imaging 9:e004136
Kwong, Raymond Y; Heydari, Bobak; Abbasi, Siddique et al. (2015) Characterization of Cardiac Amyloidosis by Atrial Late Gadolinium Enhancement Using Contrast-Enhanced Cardiac Magnetic Resonance Imaging and Correlation With Left Atrial Conduit and Contractile Function. Am J Cardiol 116:622-9
Neilan, Tomas G; Farhad, Hoshang; Mayrhofer, Thomas et al. (2015) Late gadolinium enhancement among survivors of sudden cardiac arrest. JACC Cardiovasc Imaging 8:414-423
Neilan, Tomas G; Mongeon, Francois-Pierre; Shah, Ravi V et al. (2014) Myocardial extracellular volume expansion and the risk of recurrent atrial fibrillation after pulmonary vein isolation. JACC Cardiovasc Imaging 7:1-11
Neilan, Tomas G; Bakker, Jessie P; Sharma, Bhavneesh et al. (2014) T1 measurements for detection of expansion of the myocardial extracellular volume in chronic obstructive pulmonary disease. Can J Cardiol 30:1668-75
Heydari, Bobak; Kwong, Raymond Y (2014) Response to letter regarding article, ""stress cardiac magnetic resonance imaging provides effective cardiac risk reclassification in patients with known or suspected stable coronary artery disease"". Circulation 129:e451
Shah, Ravi V; Heydari, Bobak; Coelho-Filho, Otavio et al. (2014) Vasodilator stress perfusion CMR imaging is feasible and prognostic in obese patients. JACC Cardiovasc Imaging 7:462-72

Showing the most recent 10 out of 55 publications