Underlying mechanisms of heart failure with preserved ejection fraction.

Every year 3.6 million patients are diagnosed with heart failure (HF) in Europe resulting in a socioeconomic burden of billions of Euros per year. As a consequence of our aging society as well as an improved survival of patients with cardiac morbidities, such as type 2 diabetes (T2D), hypertension and the metabolic syndrome (MetS), the incidence of HF is expected to increase by 50% in 2030. More than half of these HF patients have HF with preserved ejection fraction (HFpEF), characterized by diastolic and endothelial dysfunction, oxidative stress, myocardial stiffness, cardiac fibrosis and inflammation. As specifically the prevalence of HFpEF dramatically increases and importantly, specific prevention and treatment strategies are lacking, HFpEF represents a major unmet medical need. Altogether, this underlines the urgency to investigate the underlying mechanism(s) of HFpEF and develop specific diagnostic, prevention and treatment strategies.

Recently, our group observed capillary rarefaction, a marker for microvascular dysfunction, in a new animal model for HFpEF. However, the role of microvascular dysfunction is not investigated in the pathophysiology of HFpEF. Investigation of microvascular dysfunction in HFpEF would yield new insights in the pathology and identify novel therapeutic targets.  Moreover, by targeting risk factors, such as the comorbidity T2D, the development of HFpEF could be prevented.