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Background: In contrast to treatment for chronic HF, which is based on several large prospective randomized controlled trials, treatment for acute HF is largely based on uncontrolled studies, clinical experience and expert opinion. Perhaps at least in part related to the uncertainties in the treatment of acute HF, outcome of patients with acute HF is extremely poor. Mortality is 50% at 3 years. More than 85% of patients with acute HF are treated in the non-ICU/CCU setting -the ED and the regular medical ward. Unfortunately, appropriate treatment is particularly ill-defined in this setting. Aim: To test the hypothesis that a comprehensive approach using an early goal-directed decrement of preload and afterload with a target systolic blood pressure of 90-110 mmHg by aggressive vasodilatation in patients with acute HF in the non-ICU setting is safe, and leads to a better clinical and economical outcome.Methodology: This is a prospective, randomised controlled multicenter study designed to enrol 770 patients presenting with acute HF to the emergency department. Patients are enrolled at the University Hospital Basel, the Kantonsspital Luzern, the Kantonsspital Aarau, the University Hospital Zürich, the Kantonsspital Olten, and the Hôpital cantonal de Fribourg the University Hospital Zürich, the University Hospital Geneve, and the University Hospital Lausanne. Patients will be randomly assigned 1:1 after stratification for site and BNP levels to an early goal-directed therapy or standard care according to current ESC guidelines. Early goal-directed therapy applies aggressive vasodilatation using sublingual and transdermal nitrates, hydralazine to avoid tolerance to nitrates, and rapid up-titration of ACE-inhibitors and angiotensin receptor blockers with a target systolic blood pressure of 90-110 mmHg. Timing and dosing of diuretics and all other treatments are left to the discretion of the physician in both groups. The primary end point is death or HF readmission within 180 days. Secondary end points include the quantitative assessment of dyspnea, need for admission to the intensive care unit, surrogate markers like BNP, the digitally recorded third heart sound, renal function, time to discharge, functional status and quality of life, falls, total treatment cost, and cost-effectiveness. Patients will receive extensive clinical and economic follow-up of at least 360 days. End points will be adjudicated by a clinical end point committee blinded to group assignment.Potential significance: It is our hypothesis that a comprehensive approach using an early goal-directed therapy has the potential to more rapidly improve dyspnea, to more rapidly and more extensively reduce HF disease severity as quantified by BNP levels, and most importantly to reduce the occurrence of death and HF readmission. Due to the high cost associated with hospitalisations for HF, our study has the potential to define a novel treatment strategy that might also significantly reduce the treatment cost associated with acute HF.