Effect of Genetic Polymorphism on the Clinical Outcome of Patients with Heart Failure

Abstract

Chronic heart failure is a serious clinical disease in the modern world with a five-year mortality rate exceeding 50% and affecting approximately 1% - 2% of the adult population (Benjamin et al., 2018). Heart failure with reduced ejection fraction (HFrEF) is characterized by a multifactorial interplay of inflammatory, neurohormonal, metabolic, and genetic factors (Braunwald, 2008; Jessup & Brozena, 2003). The activation of compensatory mechanisms to maintain physiological functioning results in increased sympathetic activity, vasoconstriction, volume overload, and ventricular remodeling with deleterious effects on cardiac function (Kemp & Conte, 2012). The renin-angiotensin-aldosterone system (RAAS) is a key stimulator of the compensatory mechanisms that drive the progression of heart failure (von Lueder & Krum, 2013). Therapies that target the RAAS, such as angiotensin-converting enzyme inhibitors (ACEIs), β-blockers and mineralocorticoid receptor antagonists (MRAs), collectively inhibit the pathological compensatory mechanisms including remodeling and apoptosis of cardiomyocytes and improve clinical outcomes, and thus, are considered the foundation of HF therapy (Barrese & Taglialatela, 2013; von Lueder & Krum, 2013).