Metabolomic and cellular modifications induced by cardiac resynchronization therapy in heart failure patients. (R-7270)

Heart failure poses a tremendous medical and societal burden with every one out of nine deaths attributed to heart failure. So far, cardiac resynchronization therapy (CRT) is the only therapy that results in acute and long-term improvement in heart failure patients. Although initially designed as a treatment option to alleviate conduction disorders in the left ventricle. CRT is now a wellestablished treatment option for suitable heart failure candidates. The initial understanding of the beneficial effects harnessed by CRT was solely focused on the hemodynamic improvements induced by CRT. However, advances in molecular cardiology indicate that heart failure patients exhibit distinct molecular alterations. Given the unprecedented beneficial effect of CRT, there is a pressing need for better understanding of the molecular modifications induced by CRT. This research proposal aims at studying 1) metabolomic modifications, 2) mitochondrial function changes and 3) calcium cycling modifications induced by CRT. To achieve such fundamental insight we will use an innovative bedside to bench approach. Ultimately these results will lead to improved patient care by better pathophysiologic understanding, prognostication and patient selection. Identifying the precise molecular targets of CRT will allow for the identification of novel pathways. Potentially leading to the development of novel classes of heart failure therapy.

Keywords:Heart failure

Disciplines:Biophysics, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing