LAUSR

Acute heart failure (AHF) constitutes a heterogeneous clinical syndrome, which remains a significant challenge for everyday clinical practice, clinical research, and drug development. From the clinical perspective, AHF is characterized by high mortality rates reaching 30% within 1 year following the acute event and the increased need for repeated hospitalizations (20% within 30 days and 50% within 6 months).1 Currently available treatment modalities for AHF offer symptomatic relief in a substantial number of cases, but have failed to improve short and long term outcomes.2 Meanwhile, advances in therapeutic management of AHF have been extremely limited, with several new molecules failing to result in meaningful clinical benefits. Possible reasons for these treatment failures include diverse syndrome pathophysiology [patients with acute decompensation of chronic heart failure (ADCHF) or de novo heart failure with preserved or reduced left ventricular ejection fraction (LVEF)], heterogeneity in patient demographic and clinical characteristics, and inappropriate therapeutic targets/molecules or trial design.3 Regardless of the specific underlying pathophysiology, common contributors to AHF development include impaired cardiac mechanics, cardiac injury, vasoconstriction, endothelial dysfunction, excess neurohormonal activation, and renal dysfunction.4 Clinical manifestations in this setting are predominantly due to a combination of reduced cardiac output, increased left and right heart pressures, and systemic (venous and arterial) vasoconstriction, causing cardiac overload and venous congestion. Although AHF phenotypes share common pathophysiological pathways, the individual contribution of these pathways and the complex interplays among them result in diverse AHF phenotypes, requiring individualized management. In this regard, ADCHF with preserved or reduced LVEF is observed as part of the natural course of the syndrome, may develop during early or advanced clinical stages in patients receiving or not neurohormonal antagonists, and may be precipitated by specific factors (i.e. infection, uncontrolled