Diuretic response in acute heart failure: clinical characteristics and prognostic significance

• Published in: European heart journal 2014-05, Vol.35 (19), p.1284-1293
• Main Authors: Valente, Mattia A. E., Voors, Adriaan A., Damman, Kevin, Van Veldhuisen, Dirk J., Massie, Barrie M., O'Connor, Christopher M., Metra, Marco, Ponikowski, Piotr, Teerlink, John R., Cotter, Gad, Davison, Beth, Cleland, John G.F., Givertz, Michael M., Bloomfield, Daniel M., Fiuzat, Mona, Dittrich, Howard C., Hillege, Hans L.
• Format: Article
• Language: English
• Subjects: Acute Disease; Aged; Analysis of Variance; Atherosclerosis - complications; Bumetanide - administration & dosage; Diabetes Complications - complications; Diuretics - administration & dosage; Dose-Response Relationship, Drug; Drug Resistance; Dyspnea - prevention & control; Female; Furosemide - administration & dosage; Heart Failure - complications; Heart Failure - drug therapy; Humans; Hypotension - complications; Male; Patient Readmission; Renal Insufficiency - complications; Sulfonamides - administration & dosage; Treatment Outcome; Weight Loss - drug effects; Xanthines - administration & dosage
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehu065

Aim Diminished diuretic response is common in patients with acute heart failure, although a clinically useful definition is lacking. Our aim was to investigate a practical, workable metric for diuretic response, examine associated patient characteristics and relationships with outcome. Methods and results We examined diuretic response (defined as Δ weight kg/40 mg furosemide) in 1745 hospitalized acute heart failure patients from the PROTECT trial. Day 4 response was used to allow maximum differentiation in responsiveness and tailoring of diuretic doses to clinical response, following sensitivity analyses. We investigated predictors of diuretic response and relationships with outcome. The median diuretic response was −0.38 (−0.80 to −0.13) kg/40 mg furosemide. Poor diuretic response was independently associated with low systolic blood pressure, high blood urea nitrogen, diabetes, and atherosclerotic disease (all P < 0.05). Worse diuretic response independently predicted 180-day mortality (HR: 1.42; 95% CI: 1.11–1.81, P = 0.005), 60-day death or renal or cardiovascular rehospitalization (HR: 1.34; 95% CI: 1.14–1.59, P < 0.001) and 60-day HF rehospitalization (HR: 1.57; 95% CI: 1.24–2.01, P < 0.001) in multivariable models. The proposed metric—weight loss indexed to diuretic dose—better captures a dose–response relationship. Model diagnostics showed diuretic response provided essentially the same or slightly better prognostic information compared with its individual components (weight loss and diuretic dose) in this population, while providing a less biased, more easily interpreted signal. Conclusions Worse diuretic response was associated with more advanced heart failure, renal impairment, diabetes, atherosclerotic disease and in-hospital worsening heart failure, and predicts mortality and heart failure rehospitalization in this post hoc, hypothesis-generating study.