Metabolomics-Based Development of a Multi-Marker Panel for Estimating Patients with Heart Failure

Heart failure (HF) is a complex clinical syndrome that represents the end stage of various cardiac diseases. HF involves interplay between myocardial factors, systemic inflammation, renal dysfunction, and neurohormonal activation. It is, thus, suggested that our assessment and treatment of patients with HF should progress from a focus on improving hemodynamics to measuring and modifying the maladaptive molecular processes that contribute to progression of disease.T TOver the past 2 decades, new classes of blood-derived biomarkers have emerged that could provide improved insight into the complex processes that characterize the disease.T THowever, in view of the limited capacity of a single biomarker to improve the quality of diagnosis and effectiveness of therapy, applying a U“multi-marker approach”U that reflects the variety of molecular processes involved in HF might allow for improved diagnosis, treatment, and management. Metabolomics is a new technology aimed at identifying and quantifying a broad range (hundreds/thousands) of metabolites simultaneously, thus providing a profile of the global metabolic state of cells, tissues or organisms related to genetic settings and/or induced by endogenous (e.g. hormones) or exogenous (e.g. foods, drugs) compounds or physiopathological conditions. HF is characterized by metabolic remodeling comprising both mitochondrial dysfunction and a reduction in fatty acid oxidation rate, which is partially compensated by an increase in glucose utilization. The profile developed by metabolomics is of course a powerful platform of multi-marker approach for HF. It is a future to fully estimate a HF patient at different aspects, not only focusing on heart or a specific part of heart, but also on the whole body. This proposal is specifically designed to to explore the promising applications of metabolomics on HF. The major themes of the 3-year project are as follows: The first year X Enroll patients with HF, and divide the patients into two groups, event group and no-event group Y To investigate the difference in metabolomic analysis between these 2 groups of patients Z Prospectively clarify the prognostic role of the metabolomics-based potential multi-biomarkers in cardiac events related to HF The 2Pnd P year X Collect blood samples every 6 months from patients with full recovery at the end of the first year Y To investigate the differences in metabolomics in the same patients from being at the worst status (in the beginning) to being at the best disease status (the end of the 1Pst P year) Z To investigate the differences in metabolomics between normal controls and HF patients with full recovery at 1 year q To build up the platform of multi-biomarker for evaluating HF patients The 3Prd P year X Throughout the whole three study years, patients at stage A and B were also collected. Utilization of the information learn from the previous 2 year to build up a multi-biomarker panel, and to test whether this panel can discriminate HF patients at different stages Y To investigate the prognostic value of the multi-biomarker panel Given the novelty of the project, we have developed a working group. Our group has experts in metabolomics, integrated HF care team, statisticians, and epidemiologist. Currently, all the techniques and methods have been tested, and are up and running in our laboratory. We believe that this line of inquiry will identify the panel of the multi-marker for HF. The work has a tremendous benefit in the future either in clinical risk stratification or in setting up a platform of scientific assessment in respect to any therapeutic interventions.

Project ID:PC10207-0374
External Project ID:NSC102-2314-B182-037