Heart failure is currently one of the leading causes of death and disability worldwide, which makes it a major public health problem.1,2 Traditionally, heart failure is considered a complex syndrome with several features, including abnormal myocardial function and excessive, continuous neurohumoral activation. In this context, the current optimal pharmacological treatment of heart failure focuses on the suppression of neurohumoral activation as well as on the regulation of the fluid volume overload, haemodynamics and optimisation of heart rate control.3 However, there is accumulating evidence indicating that additional mechanisms, such as inflammatory activation and metabolic impairment, are also involved in the pathogenesis of heart failure; this evidence has stimulated the search for novel therapeutic strategies.
More than half a century ago, Richard Bing, who is often called the ‘Father of Cardiac Metabolism’, emphasised that the heart is more than a pump, it is also an organ that needs energy from metabolism.4,5 At that time, the necessity of metabolic therapy for metabolic diseases was declared. Today, multiple myocardial metabolic abnormalities in heart failure have been revealed; the heart of a patient with heart failure can be described as ‘an engine out of fuel’.6 Moreover, besides myocardial metabolic failure, systemic (peripheral) metabolic regulation has been found to contribute both to major symptoms of heart failure and to disease progression.7
In recent years, a number of promising therapies modulating the cardiac metabolism have been tested. At present, a clinically important question was raised – is there a place for metabolic modulators in the current treatment of heart failure? This article aims to review the rationale and evidence base of metabolic modulators, in particular trimetazidine, in the management of patients with heart failure.