[Heart failure. Excitation-contraction coupling and novel therapeutic options]

Abstract

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 Ca(2+) transients and SR Ca(2+) load. The Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) plays an important role in the onset of HF. CaMKIIδ phosphorylates several functional key proteins, leads to reduced SR Ca(2+) load and Ca(2+)-transients in HF, acts as an arrhythmogenic protein by increasing late I(Na), and contributes to diastolic dysfunction by accumulation of intracellular Ca(2+). CaMKIIδ also plays an important role in atrial fibrillation. Interestingly, with regard to increased cardiac load, CaMKIIδ is activated in increased afterload but not in preload. The important role of CaMKIIδ in HF implies new therapeutic options to improve HF therapy in the future.