Efficacy, Safety and Tolerability of Serelaxin When Added to Standard Therapy in AHF

Key Inclusion Criteria: * Male or female 18 years of age, with body weight ≤160 kg * Hospitalized for AHF with anticipated requirement of IV therapy for at least 48 hours; AHF is defined as including all of the following measured at any time between presentation (including the emergency department) and the end of screening: * Persistent dyspnea at rest or with minimal exertion * Pulmonary congestion on chest radiograph * B-type natriuretic peptide (BNP) ≥500 pg/mL or N-terminal (NT)-proBNP ≥2000 pg/mL; for patients ≥ 75 years of age or with current atrial fibrillation (at the time of randomization), BNP ≥ 750 pg/mL or NT-proBNP ≥ 3,000 pg/mL * Systolic BP ≥125 mmHg at the start and at the end of screening * Able to be randomized within 16 hours from presentation to the hospital, including the emergency department * Received intravenous furosemide of at least 40 mg total (or equivalent) at any time between presentation (this includes outpatient clinic, ambulance, or hospital including emergency department) and the start of screening for the study for the treatment of the current acute HF episode. Key Exclusion Criteria: * Dyspnea primarily due to non-cardiac causes * Known history of respiratory disorders requiring the daily use of IV or oral steroids (does not include inhaled steroids); need for intubation or the current use of IV or oral steroids for chronic obstructive pulmonary disease (COPD) * Temperature \>38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment * Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrollment. * AHF due to significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate \<45 beats per minute, or atrial fibrillation/flutter with sustained ventricular response of \>130 beats per minute * Patients with severe renal impairment defined as pre-randomization estimated glomerular filtration rate (eGFR) \< 25 mL/min/1.73m2 calculated using the Simplified Modification of Diet in Renal Disease (sMDRD) equation, and/or those receiving current or planned dialysis or ultrafiltration * Patients with hematocrit \<25%, or a history of blood transfusion within the 14 days prior to screening, or active life-threatening GI bleeding. * Known hepatic impairment (as evidenced by total bilirubin \> 3 mg/dL, or increased ammonia levels, if performed) or history of cirrhosis with evidence of portal hypertension such as varices. * Significant, uncorrected, left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or severe aortic stenosis (i.e., aortic valve area \<1.0 cm2 or mean gradient \>40 mmHg on prior or current echocardiogram), and severe mitral stenosis * Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated. * Documented, prior to or at the time of randomization, restrictive amyloid myocardiopathy, OR acute myocarditis or hypertrophic obstructive, restrictive, or constrictive cardiomyopathy (does NOT include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).