Combining Diuretic Response and Hemoconcentration to Predict Rehospitalization After Admission for Acute Heart Failure.
Both diuretic response and hemoconcentration are indicators of decongestion and have individually been found to predict rehospitalization after admission for acute heart failure (HF). This study examines the value of combining diuretic response and hemoconcentration to better predict patients at low risk for rehospitalization after admission for acute HF.



Diuretic response (defined as weight change per 40 mg of furosemide on day 4 after admission) and hemoconcentration (change in hemoglobin at discharge or day 7) were tested both individually and combined to predict the risk of HF and cardiovascular rehospitalization 60 days after hospitalization for acute HF. Analyses were performed in 1180 patients enrolled in the Placebo-Controlled Randomized Study of the Selective Adenosine Receptor Antagonist Rolofylline for Patients Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function (PROTECT) trial and validated in 1776 patients enrolled in the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST) trial. Poor diuretic response was associated with low systolic blood pressure, high blood urea nitrogen, and history of coronary revascularization in both data sets (all P<0.05). Hemoconcentration was mainly associated with better renal function (P<0.05). Patients who displayed both favorable diuretic response and hemoconcentration had a markedly lower risk of rehospitalization for HF in PROTECT (multivariable HR, 0.41; 95% CI, 0.24 to 0.70; P<0.001) compared with all other patients. This finding was confirmed in EVEREST (multivariable HR, 0.52; 95% CI, 0.33 to 0.82; P=0.004) for patients with favorable diuretic response and hemoconcentration compared with all other patients.



Combining 2 indicators of decongestion, hemoconcentration and diuretic response improves risk prediction for early rehospitalization after an admission for acute HF and may provide clinicians with an easily accessible tool to identify low-risk patients.



URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00354458 and NCT00071331.
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Jozine M
JM
Ter Maaten
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Mattia A E
MA
Valente
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Kevin
K
Damman
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
John G
JG
Cleland
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Michael M
MM
Givertz
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Marco
M
Metra
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Christopher M
CM
O'Connor
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
John R
JR
Teerlink
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Piotr
P
Ponikowski
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Daniel M
DM
Bloomfield
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Gadi
G
Cotter
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Beth
B
Davison
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Haris
H
Subacius
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Dirk J
DJ
van Veldhuisen
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Peter
P
van der Meer
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Hans L
HL
Hillege
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.).
Mihai
M
Gheorghiade
From the Departments of Cardiology (J.M.t.M., M.A.E.V., K.D., D.J.v.V., P.v.d.M., H.L.H., A.A.V.) and Epidemiology (H.L.H.), University of Groningen, University Medical Center Groningen, The Netherlands; University of Hull, Kingston Upon Hull, United Kingdom (J.G.C.); Brigham and Women's Hospital, Boston, MA (M.M.G.); University of Brescia, Italy (M.M.); Inova Heart and Vascular Institute, Falls Church, VA (C.M.O.C.); University of California at San Francisco, San Francisco Veterans Affairs Medical Center, CA (J.R.T.); Medical University, Clinical Military Hospital, Wroclaw, Poland (P.P.); Merck Research Laboratories, Rahway, NJ (D.M.B.); Momentum Research, Durham, NC (G.C., B.D.); University of Iowa Carver College of Medicine Cardiovascular Research Center Iowa City, IA (H.S., M.G.); and Center for Cardiovascular Innovation, Northwestern University Feinberg School of Medicine, Chicago, IL (H.S., M.G.). a.a.voors@umcg.nl.
Adriaan A
AA
Voors
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003661:Decision Support Techniques; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005665:Furosemide / Q000009:adverse effects / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010359:Patient Readmission; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D000077602:Tolvaptan; D016896:Treatment Outcome; D014970:Xanthines / Q000009:adverse effects / Q000627:therapeutic use*
D001552:Benzazepines; D015415:Biomarkers; D004232:Diuretics; D006454:Hemoglobins; D014970:Xanthines; D000077602:Tolvaptan; C073525:rolofylline; D005665:Furosemide
diuretics; heart failure; hemoglobin; hospitalization