References
Understanding the pharmacology of heart failure

Abstract
Heart failure (HF) is a common clinical syndrome with ever-increasing prevalence in the Western world. It is associated with extensive morbidity and mortality, as well as being a significant burden on global healthcare systems. It is due to impairment of ventricular filling or contraction, resulting in a constellation of physical symptoms and signs, primarily due to salt and water retention. An understanding of the pharmacological options to manage the condition is imperative to quickly alleviate symptoms and avert a rapidly progressive downward spiral, improving not only quality but also quantity of life.
Heart failure (HF) is a common clinical syndrome with ever-increasing prevalence in the Western world. It is associated with extensive morbidity and mortality, as well as being a significant burden on global healthcare systems with at least 26 million people affected worldwide (Savarese and Lund, 2017). According to the most recent National HF Audit in 2019, around 900 000 individuals have HF in the UK and the disease consumes up to 2% of the total NHS expenditure (McDonagh et al, 2019).
Thus, understanding the pathophysiology and the pharmacological treatment behind the failing heart is imperative in optimally managing the condition at an early stage, averting the potential downward spiral, and hence improving not only quality but also the quantity of life.
HF is defined by the American College of Cardiology/American Heart Association (ACC/AHA) as a complex clinical syndrome that occurs from any structural or functional impairment of ventricular filling or ejection of blood (Yancy et al, 2013). Ejection fraction (EF) represents the percentage of blood pumped out of the left ventricle of the heart with each beating. HF falls under two main groups: HF with reduced ejection fraction (HFrEF), also known as systolic dysfunction, and HF with preserved ejection fraction (HFpEF), also known as diastolic dysfunction (Yancy et al, 2013). According to ACC/AHA, HFrEF is indicated by an EF of ≤40%. It develops when the left ventricle fails to contract normally and to pump with the force needed to eject enough blood into the circulation (Yancy et al, 2013). It is important to note individuals with systolic dysfunction (HFrEF) generally have elements of diastolic dysfunction as well. HFpEF is indicated by EF of ≥50% and generally occurs due to long-standing high blood pressure that leads to thickening of the heart muscle, which results in impaired filling of the left ventricle (Yancy et al, 2013; McDonagh et al, 2019). Individuals with EF values between 40-50% represent an intermediate or borderline group. The focus of this article, unless indicated otherwise, is the pharmacological treatment of the most common type of HF, which is HFrEF.
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