Novel Therapies in Heart Failure

Abstract

Heart failure (HF) is a complex clinical syndrome that results from any structural or functional impairment of ventricular filling or ejection of blood. The cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary and/ or splanchnic congestion and/or peripheral edema (O'Riordan, 2014). There is no single diagnostic test for HF because it is largely a clinical diagnosis based on a careful history and physical examination. The clinical syndrome of HF may result from disorders of the pericardium, myocardium, endocardium, heart valves, or great vessels or from certain metabolic abnormalities, but most patients with HF have symptoms due to impaired left ventricular (LV) myocardial function. It should be emphasized that HF is not synonymous with either cardiomyopathy or LV dysfunction; these latter terms describe possible structural or functional reasons for the development of HF (Hunt et al., 2009). The lifetime risk of developing HF is 20% for Americans ≥ 40 years of age. In the United States, HF incidence has largely remained stable over the past several decades, with > 650 000 new HF cases diagnosed annually. HF incidence increases with age, rising from approximately 20 per 1000 individuals 65 to 69 years of age to >80 per 1000 individuals among those ≥85 years of age. Approximately 5.1 million persons in the United States have clinically manifest HF, and the prevalence continues to rise (Fung et al., 2008). There are two classifications for HF the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) stages of HF and the New York Heart Association (NYHA) functional classification provide useful and complementary information about the presence and severity of HF. The ACCF/AHA stages of HF emphasize the development and progression of disease and can be used to describe individuals and populations, whereas the NYHA classes focus on exercise capacity and the symptomatic status of the disease (Little et al., 1994). Non pharmacological management of HF includes exercise, diet, and nutrition. Restriction of activity promotes physical deconditioning, so physical activity should be encouraged. However, limitation of activity is appropriate during acute heart failure exacerbations and in patients with suspected myocarditis. Dietary sodium restriction and fluid restriction are recommended for patients with evidence of hyponatremia and for those whose fluid status is difficult to control. Caloric supplementation is recommended for patients with evidence of cardiac cachexia (Dickstein et al., 2008). Conventional management of HF includes diuretics, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), hydralazine, nitrates, beta-adrenergic blockers, aldosterone antagonists, Digoxin, Anticoagulants and inotropic agents and device therapy like Implantable Cardioverter Defibrilator (ICD) and Cardiac Resynchronization Therapy (CRT) (Flather et al., 2000). Novel therapies For HF are promising as Angiotensin receptor-neprilysin inhibition with LCZ696, new aldosterone receptor blockers, serelaxin, ularitide, etc (McMurray et al., 2013).