raas optimization for acute chf patients

Conditions: Acute Decompensated Heart Failure

Summary: holding acei/arbs during initial 72 hours of admission with acute decompensated heart failure may help preserve renal function with a lesser decline in gfr. this treatment modification will also allow the option of aggressive diuresis in volume overloaded chf patients which should result in a lesser decline of aki, length of stay, readmission rates, and cost associated with chf treatment.

the investigators hypothesize that worsening renal function can be mitigated by withholding acei/arb during the initial phase of in-patient treatment with aggressive diuresis. this hypothesis will be tested by randomly allocating 360 admitted patients with adhf on two treatment paths: 1) no acei/arb administered for initial 72 hours of treatment during aggressive diuresis versus 2) full dose acei/arb administered concurrently with aggressive diuresis in naïve patients/home dose, who are already on such therapy. the study team hopes to find that holding acei/arbs during the initial 72 hours of admission with acute decompensated systolic heart failure will help preserve renal function, as demonstrated by a lesser decline in gfr. in addition, this treatment would allow the option of aggressive diuresis in volume overloaded chf patients, resulting in a lesser decline of aki, length of stay, readmission rates, and costs associated with chf treatment. by understanding the complex interaction between holding aceis/arbs and continued aggressive diuresis, the investigators intend to develop optimal dosing strategies for acute, decompensated chf patients, further minimizing adverse events such as electrolyte issues and declining gfr/aki.

Eligibility criteria:
inclusion criteria: patients are eligible for enrollment if within the previous 24 hours they were treated with acute decompensated heart failure or diagnosed on the basis of the investigator's clinical diagnosis of heart failure, which needs to be supported by at least 2 the following criteria: * elevated concentration of b-type natriuretic peptide (bnp) or n-terminal pro-bnp. (elevated bnp" defined as \>300 for sinus rhythm, \>500 for patients will atrial fibrillation and elevated pro bnp defined as \>1000 for sinus rhythm, \>1600 for atrial fibrillation.) * pulmonary edema on physical examination. * radiologic pulmonary congestion or edema. * history of chronic heart failure. anticipated need for iv loop diuretics for at least 48 hours * willingness to provide informed consent exclusion criteria: * previously diagnosed end-stage renal disease; serum potassium \>5.5 mmol/l * cardiogenic shock within 48 hours, st-segment elevation myocardial infarction, ongoing ischemia. * need for renal replacement therapy through dialysis or ultrafiltration * myocardial infarction within 30 days of screening. * patients with systolic blood pressure of less than 90 mm hg. * patients requiring intravenous vasodilators or inotropic agents (other than digoxin) for heart failure * bnp less than 250 ng/ml and/or probnp less than 1000 mg/ml * pregnant women, prisoners, and institutionalized individuals * severe stenotic valvular disease * complex congenital heart disease * need for mechanical hemodynamic support * sepsis * terminal illness (other than hf) with expected survival of less than one year * previous adverse reaction to the study drugs * use of iv iodinated radiocontrast material in last 72 hours or planned during hospitalization * enrollment or planned enrollment in another randomized clinical trial during this hospitalization * inability to comply with planned study procedures * primary admission diagnosis other than acute heart failure

Keywords: acei (angiotensin-converting-enzyme inhibitor) arb (angiotensin ii receptor blocker) chf (congestive heart failure) raas (renin angiotensin aldosterone system)