According to the ejection fraction, patients with heart failure may be divided into two different groups: heart failure with preserved or reduced ejection fraction. In recent years, accumulating studies showed that increased mortality and morbidity rates of these two groups are nearly equal. More importantly, despite decline in mortality after treatment in regard to current guideline in patients with heart failure with reduced ejection fraction, there are still no trials resulting in improved outcome in patients with heart failure with preserved ejection fraction so far. Thus, novel pathophysiological mechanisms are under development, and other new viewpoints, such as multiple comorbidities resulting in increased non-cardiac deaths in patients with heart failure and preserved ejection fraction, were presented recently. In this review, we will focus on the tested as well as the promising therapeutic options that are currently studied in patients with heart failure with preserved ejection fraction, along with a brief discussion of pathophysiological mechanisms and diagnostic options that are helpful to increase our understanding of novel therapeutic strategies. 1. Introduction Heart failure (HF) with preserved ejection fraction (HFPEF) has been well recognized as an increasing epidemiological and medical challenge over the last two decades [1, 2]. Studies indicate that the number of patients with HFPEF is similar or even higher compared to the number of patients with HF with reduced ejection fraction (HFREF) [3, 4]. Moreover, we do know that the mortality is similar in patients with HFPEF compared to HFREF [5]. However, the conventional medical therapies in HFREF, that are based on the strong evidence of multiple randomized controlled clinical trials (RCTs) showing a decline in mortality, have shown no favourable result in HFPEF so far [6, 7]. A recent study also showed that noncardiac deaths in HFPEF are higher than in HFREF, which could be a result of multiple complicating diseases in patients with HFPEF [8]. This review will focus on the tested and upcoming treatment options in HFPEF. Moreover, pathophysiological mechanisms and diagnostic options will also be briefly discussed in order to understand new therapeutic targets in this field. 2. Diagnosis of HFPEF According to the latest recommendations of the European Society of Cardiology and American Heart Association [6, 7], there are, although this is still under intensive discussion, at least three criteria for the diagnosis of HFPEF: clinical signs and/or symptoms of HF, normal or mild reduction of
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