Metabolic approach to heart failure: The role of metabolic modulators

Heart failure (HF) is a systemic and multiorgan syndrome with metabolic failure as fundamental mechanism. As a consequence of its impaired metabolism, other processes are activated in the failing heart, further exacerbating the progression of HF.Metabolic agents are a relatively new class of drugs that act through optimisation of cardiac substrate metabolism. Among the metabolic modulators, Trimetazidine (TMZ) and perhexiline are the only two agents with proven anti-ischaemic effect currently available. However, due to its major side effects, perhexiline is not yet approved in the US or Europe.Clinical trials have demonstrated that the adjunct of TMZ to optimal medical therapy improves symptoms and prognosis of HF without exerting negative hemodynamic effects. Due to its anti-ischaemic/anti-anginal effect and excellent tolerability, the modulation of cardiac metabolism with TMZ represents a promising approach for the treatment of patients with HF.