Heart failure. Excitation-contraction coupling and novel therapeutic options

Heart failure (HF) is a disease with an increasing prevalence and results in both reduced quality of life and decreased lifespan for patients. Despite improved therapy mortality remains very high. HF is induced by events that lead to reduced function of the heart, e.g. myocardial infarction and increased chronic afterload through arterial hypertension. For compensation to occur, neurohumoral mechanisms temporarily maintain cardiac function. Over time this results in left ventricular remodelling and, by means of a vicious circle, compensated HF becomes symptomatic HF. The myocardium of patients with HF is characterised by a dysfunction in excitation-contraction coupling (ECC), which causes reduced cell contractility due to reduced Ca²⁺ transients and SR Ca²⁺ load. The Ca²⁺/calmodulin-dependent protein kinase II?? (CaMKII??) plays an important role in the onset of HF. CaMKII?? phosphorylates several functional key proteins, leads to reduced SR Ca²⁺ load and Ca²⁺-transients in HF, acts as an arrhythmogenic protein by increasing late I_Na, and contributes to diastolic dysfunction by accumulation of intracellular Ca²⁺. CaMKII?? also plays an important role in atrial fibrillation. Interestingly, with regard to increased cardiac load, CaMKII?? is activated in increased afterload but not in preload. The important role of CaMKII?? in HF implies new therapeutic options to improve HF therapy in the future.