Heart failure (HF) has emerged as the greatest current challenge in cardiovascular medicine. Detection of subclinical cardiac dysfunction could give us a unique opportunity to treat patients at an earlier stage of disease and to modify the risk factors to prevent or slow HF development and progression. In HF with dilated non-ischemic cardiomyopathy (NICM), early changes in extracellular matrix volume (ECV) and formation of myocardial fibrosis and inflammation result in impairment of ventricle function and precipitation of arrhythmias. Therefore, early detection of these changes could have significant clinical impact. Cardiovascular magnetic resonance (CMR) is a non-invasive, multifaceted, powerful imaging modality that employs no ionization radiation, has high spatial resolution and provides excellent soft tissue contrast. Myocardial T1 and T2 relaxation times change in the presence of interstitial diffuse fibrosis and inflammation. A major limitation of current CMR technique is use of semi-quantitative and subjective assessment of disease status. Novel advances in CMR allow voxel-wise quantification of relaxation times to characterize myocardial tissue composition, analogous to myocardial regional biopsy, as a unique and powerful tool which is unparalleled by any other imaging modality. We have recently developed novel approaches to accurately measure in-vivo myocardial T1 and T2 times. In this study, we propose to continue development, refinement and multi-center/multi-vendor evaluation of our multi-slice T1 and T2 mapping sequences. Concurrently, in a pilot clinical study, we will assess the predictive value of T1, T2 and ECV in patients with newly recognized dilated NICM for HF progression and adverse cardiac events over a 2-year clinical follow up. We will also assess incremental value of CMR vs. non-CMR markers of HF progression and adverse cardiac events.

Public Health Relevance

Heart failure is now considered to be the greatest challenge in cardiovascular medicine. Patients with newly diagnosed dilated non-ischemic cardiomyopathy and reduced LV ejection fraction (LVEF) are initially managed using optimal medical therapy and LVEF recovery is monitored using transthoracic echocardiography. Over subsequent 3-12 months 1/3 of these patients will have LVEF recovery, 1/3 will remain the same and 1/3 w ill deteriorate with multiple hospitalizations. However, it is still unknown why some patients recover, but not others. Diffuse Myocardial fibrosis and inflammation play major roles in disease progression and future adverse events. Therefore, the overall objective of this proposal is 1) to evaluate our recently developed whole heart non-invasive quantitative imaging methods to assess myocardial fibrosis and inflammation, 2) to assess the predictive value of novel markers of inflammation and fibrosis in identifying newly diagnosed dilated cardiomyopathy patients who are at risk of developing heart failure, and 3) to assess incremental predictive value of CMR vs. non-CMR parameters for LV remodeling and adverse cardiac events.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Danthi, Narasimhan
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Beth Israel Deaconess Medical Center
United States
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