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ONLINE APPENDIX
Data collection
We searched for prospective studies of patients hospitalized for ADHF between January, 1966
and January, 2010 (Medline/ Embase, PubMed, Cochrane and bibliographies of expert
advisors). We identified seven prospective cohort studies eligible for inclusion (1-7). The
principal investigators of six of the seven studies agreed to perform a collaborative analysis
(1-3, 5-7). In addition, we added our own Dutch cohort of patients admitted for ADHF, which
was part of a registry at the Academic Medical Center (AMC) in Amsterdam. All studies were
approved by the ethical commission in their respected centers and for the conduction of the
current study we again received the approval of the ethical commission. One study was
excluded, because creatinine values at discharge were not available (1). Because of the above
exclusions the numbers of patients reported here may differ from those in the original
publications.
Definitions
Worsening renal function (WRF) was defined as an absolute increase in serum creatinine
level of >0.3 mg/dl in combination with >25% increase in serum creatinine level between
admission and discharge (8, 9). We defined severe worsening renal function (sWRF) as an
absolute increase in serum creatinine level of >0.5 mg/dl in combination with >25% increase
in serum creatinine level between admission and discharge. The effect of NT-proBNP was
evaluated using ≤30% or >30% percentage reduction between admission and discharge which
was based on previous studies (1, 2, 5, 10). However, in the multivariable model we also
adjusted for NT-proBNP value at discharge (>5000 pg/ml), because we showed in our
previous work that both values are independent predictors of mortality (10). Worsening serum
urea nitrogen was defined as a ≥25% increase during hospitalisation and worsening eGFR
(Estimated Glomerular Filtration Rate was calculated as 186.3 x (Creatinine mg/dl)^-1.154 x
(Age)^-0.203 x (0.742 if female) x (1.210 if black) was defined as a ≥25% decrease based on
previously published studies (11, 12, 13). The baseline cut-off levels for systolic blood
pressure (SBP ≤115 mm/Hg), eGFR (<30 mL/min/1.73m²) and serum urea nitrogen (≥15
mmol/l) levels were also based on previously published studies (10, 12, 14-17). The cut-off
levels for anemia (hemoglobin <129 g/l (8 mmol/l) in men, <121 g/L (7.5mmol/l) in women)
and hyponatremia (sodium <135 mmol/l) were based on ESC guidelines (18).
Reference List
1. Bayés-Genís A, Lopez L, Zapico E, et al. NT-ProBNP reduction percentage during
admission for acutely decompensated heart failure predicts long-term cardiovascular
mortality. J Card Fail 2005; 11:S3-S8.
2. Bettencourt P, Azevedo A, Pimenta J, Friões F, Ferreira S, Ferreira A. N-terminal-probrain natriuretic peptide predicts outcome after hospital discharge in heart failure
patients. Circulation 2004; 110:2168-74.
3. Eurlings LW, van Pol PE, Kok WE, et al. Management of chronic heart failure guided
by individual N-terminal pro-B-type natriuretic peptide targets: results of the PRIMA
(Can PRo-brain-natriuretic peptide guided therapy of chronic heart failure IMprove
heart fAilure morbidity and mortality?) study. J Am Coll Cardiol 2010; 56:2090-100.
4. Kubler P, Jankowska EA, Majda J, Reczuch K, Banasiak W, Ponikowski P. Lack of
decrease in plasma N-terminal pro-brain natriuretic peptide identifies acute heart
failure patients with very poor outcome. Int J Cardiol 2008; 129:373-8.
5. Metra M, Nordari S, Parrinello G, et al. The role of plasma biomarkers in acute heart
failure. Serial changes and independent prognostic value of NT-proBNP and cardiac
troponin-T. Eur J Heart Fail 2007; 9:776-86.
6. Pimenta JM, Almeida R, Araújo JP, et al. Amino terminal B-type natriuretic peptide,
renal function, and prognosis in acute heart failure: a hospital cohort study. J Card Fail
2007; 13:275-80.
7. Verdiani V, Ognibene A, Rutili MS, et al. NT-ProBNP reduction percentage during
hospital stay predicts long-term mortality and readmission in heart failure patients. J
Cardiovasc Med 2008; 9:694-9.
8. Damman K, Jaarsma T, Voors AA, Navis G, Hillege HL, van Veldhuisen DJ. Both inand out-hospital worsening of renal function predict outcome in patients with heart
failure: results from the Coordinating Study Evaluating Outcome of Advising and
Counseling in Heart Failure (COACH). Eur J Heart Fail 2009; 11:847-54.
9. Metra M, Nodari S, Parrinello G, et al. Worsening renal function in patients
hospitalised for acute heart failure: clinical implications and prognostic significance.
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10. Salah K, Kok WE, Eurlings LW, et al. A novel discharge risk model for patients
hospitalised for acute decompensated heart failure incorporating N-terminal pro-Btype natriuretic peptide levels: a European coLlaboration on Acute decompeNsated
Heart Failure: ELAN-HF Score. Heart 2014; 100:115-25.
11. Blair JE, Pang PS, Schrier RW, et al. Changes in renal function during hospitalization
and soon after discharge in patients admitted for worsening heart failure in the placebo
group of the EVEREST trial. Eur Heart J 2011; 32:2563-72.
12. Klein L, Massie BM, Leimberger JD, et al. Admission or changes in renal function
during hospitalization for worsening heart failure predict postdischarge survival:
results from the Outcomes of a Prospective Trial of Intravenous Milrinone for
Exacerbations of Chronic Heart Failure (OPTIME-CHF). Circ Heart Fail 2008; 1:2533.
13. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC guidelines for the diagnosis and
treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and
treatment of acute and chronic heart failure 2008 of the European Society of
Cardiology. Developed in collaboration with the Heart Failure Association of the ESC
(HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).
Eur J Heart Fail 2008; 10:933-89.
14. Fonarow GC, Adams KFjr, Abraham WT, Yancy CW, Boscardin WJ. Risk
stratification for in-hospital mortality in acutely decompensated heart failure:
classification and regression tree analysis. JAMA 2005; 293:572-80.
15. Hillege HL, Nitsch D, Pfeffer MA, et al. Renal function as a predictor of outcome in a
broad spectrum of patients with heart failure. Circulation 2006; 113:671-8.
16. Khan NA, Ma I, Thompson CR, et al. Kidney function and mortality among patients
with left ventricular systolic dysfunction. J Am Soc Nephrol 2006; 17:244-53.
17. Lee D, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV. Predicting mortality
among patients hospitalized for heart failure: derivation and validation of clinical
model. JAMA 2003; 290:2581-7.
18. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and
treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis
and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of
Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of
the ESC. Eur J Heart Fail 2012; 14:803-69.