As outlined above, heart failure is a highly complex patho¬physiological entity. There are numerous approaches to patient characterization, symptom-orientated (NYHA class), according to clinical assessments (e.g. estimation of ejection fraction), according to the activity of compensatory mechanisms (e.g. levels of neuroendocrine activation), or according to the degree of secondary damage (e.g. degree of insulin resistance). These factors are further complicated, for example, by the underlying disease, such as ischaemic heart disease or atherosclerosis per se. SICA-HF aims to embrace different approaches to heart failure characterization and will recruit patients at all stages of the syndrome. This includes even a healthy control cohort and patients with diabetes without heart failure, because these patients are deemed to be at high risk of developing heart disease and heart failure. The pathophysiology of heart failure may vary considerably between different stages of the disease. Importantly, the development of co-morbidities such as type 2 diabetes, obesity, and cachexia may influence pathophysiological pathways. The SICA-HF consortium is convinced that these subgroups of patients may benefit from tailored therapies that take these pathophysiological aterations into account. A thorough understanding of the pathophysiology of these important alterations is therefore crucial to future therapeutic endeveaours. Indeed, almost all mechanisms, and possibly therapeutics relevant for heart failure may be either beneficial or detrimental, depending on timing, context, and preexisting confounding factors. The members of this consortium are convinced and have analyzed this already in several publications that a comprehensive, 'holistic' approach will be key to disentangling the complexities and to developing successful therapeutic strategies.
The overall strategy of our workplan is to address, in a highly concerted and integrated fashion, the whole sequence of events, from non-existing to subclinical and finally overt heart failure across the entire spectrum of events and clinical symptoms. Importantly, we will consider gender aspects (we will recruit 50% women) and the entire cascade from the two extreme ends of the body weight spectrum (cachexia and obesity) to patients with type 2 diabetes and the full metabolic syndrome. The combination of preclinical and clinical approaches will help in disentangling pathways for future novel therapeutic approaches.