For patients hospitalized with acute decompensated heart failure,volume removal remains the primary therapeutic objective. The current standard of care remains loop diuretics.The high likelihood of readmissions and poor outcomes highlights the need to examine and improve in-hospital protocols for these patients. Ultrafiltration allows for greater volume removal, less neurohormonal stimulation and greater sodium removal.However it is associated with increased costs, line complications, and relative immobility during treatment. Tolvaptan in addition to diuretic therapy has been shown to improve the amount of volume removed compared to diuretic alone.

The study proposes to compare the strategy of adding tolvaptan to usual care with ultrafiltration as primary mode of therapy in acute decompensated HF(ADHF) patients.

Hypothesis: addition of tolvaptan to usual care for hospitalized HF patients will result in:

• greater volume and weight reduction compared with usual care
• similar efficacy outcomes compared with ultrafiltration, with less complications of therapy

Study design is a prospective randomized open labeled and unblinded comparison of two different approaches to volume removal. Enrolled patients will be evaluated for target weight to be removed. Patients will be randomized to usual care (UC), usual care plus tolvaptan (UC+T) or ultrafiltration (UF), within 12 hours of presentation.

Treatment in the UC and UC+T arms will begin with a furosemide bolus(double the home dose or if unavailable, 60mg) and continue with a drip(10 or 20 mg/hr). In addition the UC+T group will be treated with tolvaptan 30 mg orally once daily.

Patients in the UF arm will be treated with UF administered through a brachial line or a catheter in the internal jugular vein. Loop and thiazide diuretics will be discontinued, although aldosterole antagonists will be continued.

Urinary neutrophil gelatinase associated lipocalcin(uNGAL)levels are elevated in renal dysfunction and may be a sensitive biomarker to distinguish between intrinsic renal damage and reversible, transient prerenal azotemia.Characterizing the changes in uNGAL levels during the course of ADHF therapy, in comparison with patient weight, BUN and creatinine levels is an important step in establishing the role of this potential promising biomarker in ADHF treatment strategies.

Protocol highlights for all patients include:

Baseline labs and daily through day 4 and at discharge(BMP, BNP, CBC, urine creatinine and sodium, uNGAL)

• Daily am weights
• Daily volume status:total intake, urine output, ultrafiltrate volume
• Collect all urine and ultrafiltrate in a 24 hour collection bag, record volume, creatinine and Na levels
• length of stay
• hospital day 4: Minnesota Living with Heart Failure questionnaire
• Cost of hospitalization

Inclusion Criteria:

• 2 of 3 physical exam findings of volume overload (rales, JVP over 5 cm and edema)
• BNP over 300
• no contraindication to ultrafiltration (line insertion, heparin use)

Exclusion Criteria:

• serum creatinine > 3mg/dL or Na > 145
• inotrope or vasopressor dependency
• active infection, including urinary tract
• resynchronization therapy or coronary intervention in past 30 days
• life expectancy less than 6 months
• hypertrophic obstructive cardiomyopathy with peak resting gradient > 20 mmHg
• IV contrast or NSAID use in the past 1 week (uNGAL related requirement)