Characteristics and Outcomes Associated With Worsening Heart Failure | Journal Scan

Study Questions:

What are the patient characteristics and outcomes associated with worsening heart failure (WHF)?


The study investigators pooled individual patient data for analysis from the PROTECT (Placebo-Controlled Randomized Study of the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function) and RELAX-AHF (Efficacy and Safety of Relaxin for the Treatment of Acute Heart Failure) phase II and III studies.


The study cohort was comprised of 3,691 patients. In 10-15% of these patients, death or WHF occurred through day 5. The study investigators found that a multivariable model, incorporating baseline demographics, medical history, and clinical assessments, provided modest discrimination between patients who did or did not develop WHF (C-index -0.68). The strongest predictor of WHF in the pooled database was blood urea nitrogen (BUN). Using multivariate analysis, they found that WHF was associated with a mean increase in length of hospital stay of 5.2 days (95% confidence interval [CI], 4.6-5.8 days) and increased risks of 60-day HF or kidney failure readmission or cardiovascular mortality (hazard ratio [HR], 1.64; 95% CI, 1.34-2.01) and 180-day mortality (HR, 1.93; 95% CI, 1.55-2.41) (all p < 0.001). The risk of death was greater when intravenous inotropes or mechanical therapy was utilized in WHF (HR, 3.03; 95% CI, 2.11-4.36) compared with patients whose WHF was treated with intravenous loop diuretic alone (HR, 1.80; 95% CI, 1.36-2.36) (both p < 0.001). Greater increase in markers of kidney and liver dysfunction during the first days of admission was associated with WHF, and despite adjusting for these variables, WHF remained a poor prognostic sign.


The study investigators concluded that WHF during the first 5 days of admission for AHF occurred in approximately 10-15% of patients, and was associated with longer length of hospital stay and higher risk for readmission and mortality.


This is an important study that confirms what astute heart clinicians have suspected all along about the fact that WHF occurs in sicker patients. The biggest challenge of assessing WHF in a given case is to determine what are the prime movers of dysfunction when there is both cardiac and renal dysfunction. Is it the heart or is it the kidneys or both? Successful management of acute decompensated HF will require that therapies directed against WHF will have to target both cardiac and renal dysfunction.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Blood Urea Nitrogen, Cohort Studies, Heart Failure, Hospitalization, Kidney, Length of Stay, Liver Diseases, Mortality, Multivariate Analysis, Patient Readmission, Purinergic P1 Receptor Antagonists, Relaxin, Renal Insufficiency, Sodium Potassium Chloride Symporter Inhibitors, Xanthines

< Back to Listings