Pilot Study of Using Copeptin to Predict Response to Tolvaptan

The study screening strategy will be designed to enroll an enriched patient population by identifying patients at the high or low end of the spectrum of copeptin levels for outpatients with stable heart failure. This will be accomplished by blinded review of copeptin levels obtained during screening.

The primary endpoints for analysis will be 24 hour urine output and the change in body weight over 24 hours during the inpatient stay.

Inclusion criteria

• Male and female patients with a history of chronic symptomatic heart failure, defined as dyspnea on exertion or edema, due to cardiac dysfunction, of at least one month's duration
• Left ventricular ejection fraction ≤ 45% as documented by quantitative assessment by an accepted imaging technique within one year of screening
• Meet baseline copeptin criteria for entry
• Currently taking a diuretic (with diuretic defined as any loop or thiazide diuretic or aldosterone antagonist at any dose)

Exclusion criteria

• Current New York Heart Association Functional Class IV heart failure
• Patients who are felt to be volume depleted based on clinical examination or need to reduce diuretic administration
• Presence of clinical contraindications to tolvaptan
• Episode of acute myocardial infarction or acute coronary syndrome within the past 3 months
• Cardiovascular surgical procedure within the past 4 weeks
• CHF due to uncorrected thyroid disease, active myocarditis, or known amyloid cardiomyopathy.
• History of primary significant liver disease or acute hepatic failure, as defined by the investigator.
• Chronic uncontrolled diabetes mellitus as determined by the investigator.
• Supine systolic arterial blood pressure < 90 mmHg at screening
• Serum creatinine > 3.5 mg/dL at screening
• Serum potassium > 5.5 mEq/L or < 3.5 mEq/L at screening
• Subjects currently treated with hemofiltration or dialysis

j. Subjects judged by the investigator to be unable to maintain accurate intake and output during their hospitalization related to medical or other problems