• Patient well being, as determined by a visual analog scale [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
• Change in serum creatinine [ Time Frame: Measured at baseline and after 72 hours ] [ Designated as safety issue: Yes ]

• Efficacy measure will be patient reported global well being by visual analog scale (VAS) quantified as the area under the curve (AUC) over 72 hours. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
• Safety measure will be change in serum creatinine from baseline to 72 hours. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]

• Weight loss [ Time Frame: Measured at 24, 48, 72, and 96 hours ] [ Designated as safety issue: No ]
• Proportion of patients free of congestion [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: No ]
• Change in the bivariate relationship of creatinine versus weight loss [ Time Frame: Measured at 72 hours ] [ Designated as safety issue: Yes ]
• Dyspnea, as determined by visual analog scales [ Time Frame: Measured at 24, 48, and 72 hours ] [ Designated as safety issue: No ]
• Patient global assessment, as determined by visual analog scales [ Time Frame: Measured at 24 and 48 hours ] [ Designated as safety issue: No ]
• Change in serum creatinine [ Time Frame: Measured at baseline, Hours 24, 48, and 96, and Days 7 and 60 ] [ Designated as safety issue: Yes ]
• Change in cystatin C [ Time Frame: Measured at baseline, 72 hours, and Days 7 and 60 ] [ Designated as safety issue: No ]
• Worsening or persistent heart failure, defined as a need for rescue therapy [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
• Development of cardio-renal syndrome, defined as an increase in the serum creatinine level greater than 0.3 mg/dl [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: Yes ]
• Net fluid loss [ Time Frame: Measured at 24, 48, and 72 hours ] [ Designated as safety issue: No ]
• Time from study entry to discharge during index hospitalization [ Time Frame: Measured over 72 hours ] [ Designated as safety issue: No ]
• Death or total days hospitalized for heart failure [ Time Frame: Measured over the 60 days following study entry ] [ Designated as safety issue: No ]
• Death or re-hospitalization [ Time Frame: Measured at Day 60 ] [ Designated as safety issue: No ]

• Weight Loss: Weight loss will be measured over the 96-hour study period (at 24, 48, 72, and 96 hours from randomization). [ Time Frame: 96 hours ] [ Designated as safety issue: No ]
• Proportion of Patients Free of Congestion at 72 hours: will be defined as JVP < 8 cm, no orthopnea, trace peripheral edema or less [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
• Change in the bivariate relationship of creatinine at 72 hours vs. weight loss at 72 hours. Visual and statistical assessment will reveal the "trade off" between change in weight and change in renal function. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
• Dyspnea VAS AUC over 24, 48, and 72 hours [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
• PGA VAS AUC over 24 and 48 hours [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
• Change in Serum Creatinine from baseline to 24, 48, 96 hours, day 7/discharge, and 60 days [ Time Frame: 60 days ] [ Designated as safety issue: Yes ]
• Change in Cystatin C from baseline to 72 hours, Day 7/discharge, and 60 days [ Time Frame: 60 days ] [ Designated as safety issue: No ]
• Worsening or persistent heart failure: defined as need for rescue therapy over 72 hours after randomization. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
• Development of Cardio-renal syndrome: defined as increase in serum creatinine > 0.3 mg/dl from randomization at any time point during 72 hours after randomization. [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
• Net fluid loss over study period: Assessed at 24, 48, and 72 hours. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
• Time from randomization to discharge during index hospitalization [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
• Total days hospitalized for heart failure or deceased during the 60 days after randomization. [ Time Frame: 60 days ] [ Designated as safety issue: No ]
• Death or rehospitalization (to include unscheduled clinic visits or ED visits) at 60 days. [ Time Frame: 60 days ] [ Designated as safety issue: No ]

Heart failure is a disorder in which the heart does not pump blood adequately. This can lead to several serious problems, including reduced blood flow throughout the body, congestion of blood in the veins and lungs, and fluid accumulation in various organs and limbs. Diuretics are often used to address the problem of fluid accumulation, but the optimal dose and the amount of time over which to administer each dose are unclear. This study will compare high and low doses of diuretics administered over longer and shorter periods of time to determine the safest and most effective combination.

Heart failure is a common disorder in which the heart cannot pump enough blood to meet the needs of the rest of the body. Heart failure symptoms include shortness of breath, swelling, and fatigue. Standard treatment for the swelling associated with heart failure includes the use of diuretic medications, such as furosemide, which cause urination and the removal of excess fluids in the body. Although furosemide has been used to treat heart failure patients for many years, it is still unclear how much of the drug to use, and over what time period the drug should be given. This study will evaluate whether furosemide treatment is safer and more effective when the drug is given in high doses versus low doses and in two to three separate doses versus one continuous infusion.

Participants in this study will begin study procedures within the first 24 hours of their hospital admission for heart failure. Participants will be randomly assigned to receive one of the following four treatments: high dose furosemide via continuous intravenous (IV) infusion and placebo every 12 hours via IV bolus; low dose furosemide via continuous IV infusion and placebo every 12 hours via IV bolus; high dose furosemide every 12 hours via IV bolus and placebo via continuous IV infusion; and low dose furosemide every 12 hours via IV bolus and placebo via continuous IV infusion. Each participant will receive treatment for the first 72 hours of his or her hospital stay. Participants will answer questionnaires and undergo physical examinations and blood tests during the first 96 hours of hospitalization and again before hospital discharge or on Day 7, if that occurs first. Participants will be asked to return to their doctors 60 days following hospital discharge to evaluate their responses to treatment.

• Drug: Furosemide
• Drug: Placebo

• Experimental: Participants will receive high dose furosemide administered via IV bolus every 12 hours and placebo via continuous IV infusion.
• Experimental: Participants will receive high dose IV furosemide administered via continuous infusion and placebo every 12 hours via IV bolus.
• Experimental: Participants will receive low dose furosemide administered via IV bolus every 12 hours and placebo via continuous infusion.
• Experimental: Participants will receive low dose IV furosemide administered via continuous infusion and placebo every 12 hours via IV bolus.

Inclusion Criteria:

• Prior clinical diagnosis of heart failure that was treated with daily oral loop diuretics for at least 1 month
• Current diagnosis of heart failure, as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
• Daily oral dose of furosemide between 80 mg and 240 mg (or equivalent)
• Identified within 24 hours of hospital admission
• Current treatment plan includes IV loop diuretics for at least 48 hours

Exclusion Criteria:

• Brain natriuretic peptide (BNP) less than 250 mg/mL or N-terminal prohormone brain natriuretic peptide (NT-proBNP) less than 1000 mg/mL
• Received IV vasoactive treatment or ultra-filtration therapy for heart failure since initial presentation
• Treatment plan during current hospitalization includes IV vasoactive treatment or ultra-filtration for heart failure
• Substantial diuretic response to pre-randomization diuretic dosing such that higher doses of diuretics would be medically inadvisable
• Systolic blood pressure less than 90 mm Hg
• Serum creatinine level greater than 3.0 mg/dL at baseline or currently undergoing renal replacement therapy
• Hemodynamically significant arrhythmias
• Acute coronary syndrome within 4 weeks prior to study entry
• Active myocarditis
• Hypertrophic obstructive cardiomyopathy
• Severe stenotic valvular disease
• Restrictive or constrictive cardiomyopathy
• Complex congenital heart disease
• Constrictive pericarditis
• Non-cardiac pulmonary edema
• Clinical evidence of digoxin toxicity
• Need for mechanical hemodynamic support
• Sepsis
• Terminal illness (other than heart failure) with expected survival time of less than 1 year
• History of adverse reaction to the study drugs
• Use of IV iodinated radiocontrast material within 72 hours prior to study entry or planned during hospitalization
• Enrollment or planned enrollment in another randomized clinical trial during this hospitalization
• Inability to comply with planned study procedures