A multidimensional sight on cardiac failure: uncovered from structural to molecular level.

Heart failure is one of the leading causes of death, with high mortality rate within 5 years after diagnosis. Treatment and prognosis options for heart failure primarily targeted on hemodynamic and neurohumoral components that drive progressive deterioration of the heart. However, given the multifactorial background that eventually leads to the "phenotype" named heart failure, better insight into the various components may lead to personalized treatment opportunities. Indeed, currently used criteria to diagnose and/or classify heart failure are possibly too focused on phenotypic improvement rather than the molecular driver of the disease and could therefore be further refined by integrating the leap of molecular and cellular knowledge. The ambiguity of the ejection fraction-based classification criteria became evident with development of advanced molecular techniques and the dawn of omics disciplines which introduced the idea that disease is caused by a myriad of cellular and molecular processes rather than a single event or pathway. The fact that different signaling pathways may underlie similar clinical manifestations calls for a more holistic study of heart failure. In this context, the systems biology approach can offer a better understanding of how different components of a system are altered during disease and how they interact with each other, potentially leading to improved diagnosis and classification of this condition. This review is aimed at addressing heart failure through a multilayer approach that covers individually some of the anatomical, morphological, functional, and tissue aspects, with focus on cellular and subcellular features as an alternative insight into new therapeutic opportunities.