Exploring Myocardial Lipid and Creatine as Imaging Biomarkers for Patients of Heart Failure

Heart failure (HF) is a major societal burden due to its high prevalence, poor prognosis and high cost. A potential therapeutic target is to supply the energy-starved heart. Lipid content of the heart is highly dynamic and myocardial lipid overload has been implicated in the pathophysiology of cardiac disease. The measurement of total creatine, a crucial actor in the creatine kinase system, gives an insight into the energy storage and buffering capacity in the heart. Magnetic Resonance Spectroscopy (MRS) is an imaging technique that allows non-invasive biochemical analysis in the clinical setting using routine MR scanner. It has the combined advantages of inherently providing molecular information, being free of ionizing radiation, and not requiring administration of external tracers. The objective of this 3-year project is to develop myocardial MRS, in particular lipid (triglyceride) and creatine resonances, as imaging biomarkers for patients with heart failure (HF). Investigators will elucidate how and, to what extent, lipid and creatine levels of the heart contribute to heart failure. The first year is a cross-sectional study. Investigators aim to compare the MRS of normal subjects and that of stable HF patients in recovery with normal or impaired ejection fraction (EF). Total 60 subjects will be enrolled, with 20 subjects in each group. In the 2nd and 3rd years, investigators plan a prospective longitudinal study of 40 subjects. Enrolled patients will be evaluated with cardiac MRS at three time points, i.e., disease onset, 6 months and one year after treatment, and will be followed up until the end of this project (1.5~3-year follow up). In total 120 MR scans will be performed in the 2nd and 3rd years. The resonances from cardiac MRS, including creatine and lipids, will be correlated with the disease course, patient biochemistry data and clinical outcome. Investigators expect to make MRS to become an integral part of a clinical cardiac MR protocol. The advance in knowledge is to prove the association between heart failure and myocardial impairment in lipids and/or creatine. The knowledge gained from MRS could potentially translate as a non-invasive biomarker for heart failure patients. This biomarker can help to early detect treatable causes of HF, and to monitor and evaluate treatment response in a non-invasive fashion. The inherited non-invasiveness and non-radiation nature makes MR an ideal technique for clinical application and biotechnology development.