Metabolic remodeling as a target preventing myocardial dysfunction: focus on trimetazidine

During the past decade significant declines in cardiovascular mortality have been observed due to the wider use of reperfusion and the optimization of medical therapy. Although rates of procedural success are high in patients with acute and chronic ischemic heart disease, improvement in heart function is not always achieved due to reperfusion injury, microvascular obstruction and the no-reflow syndrome. Insufficient oxygen supply and lack of metabolic adaptation lead to the activation of a complex cascade of reactions including increased reactive oxygen species production, activation of oxidative stress, cellular damage, triggering of apoptosis, progressive cell loss and deposition of extracellular collagen matrix. These mechanisms lead to heart remodeling and progression of heart failure, and have similar features to those of nonischemic cardiopathy. Malicious metabolic remodeling may be prevented by protective mechanisms such as ischemic preconditioning, heart metabolism switch to more efficient energy substrate utilization and transfer. Therefore, adjunctive metabolic medical therapy is being recognized as a reasonable therapeutic option. Of the available therapies, trimetazidine is one of the most effective drugs with confirmed clinical benefits. The mechanisms of heart protection targeted by trimetazidine are quite complex and are reviewed in this article. L Heart Metab; 2014;62:22–26