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. 2021 Jul;23(7):1122-1130.
doi: 10.1002/ejhf.2179. Epub 2021 Apr 15.

Decongestion discriminates risk for one-year mortality in patients with improving renal function in acute heart failure

Nicholas Wettersten  1   2 , Yu Horiuchi  3 , Dirk J van Veldhuisen  4 , Joachim H Ix  5 , Christian Mueller  6 , Gerasimos Filippatos  7 , Richard Nowak  8 , Christopher Hogan  9 , Michael C Kontos  10 , Chad M Cannon  11 , Gerhard A Müeller  12 , Robert Birkhahn  13 , Pam Taub  2 , Gary M Vilke  14 , Stephen Duff  15 , Kenneth McDonald  16   17 , Niall Mahon  16 , Julio Nuñez  18   19 , Carlo Briguori  20 , Claudio Passino  21 , Alan Maisel  2 , Patrick T Murray  15
Affiliations

Decongestion discriminates risk for one-year mortality in patients with improving renal function in acute heart failure

Nicholas Wettersten et al. Eur J Heart Fail. 2021 Jul.

Abstract

Aims: Improving renal function (IRF) is paradoxically associated with worse outcomes in acute heart failure (AHF), but outcomes may differ based on response to decongestion. We explored if the relationship of IRF with mortality in hospitalized AHF patients differs based on successful decongestion.

Methods and results: We evaluated 760 AHF patients from AKINESIS for the relationship between IRF, change in B-type natriuretic peptide (BNP), and 1-year mortality. IRF was defined as a ≥20% increase in estimated glomerular filtration rate (eGFR) relative to admission. Adequate decongestion was defined as a ≥40% decrease in last measured BNP relative to admission. IRF occurred in 22% of patients who had a mean age of 69 years, 58% were men, 72% were white, and median admission eGFR was 49 mL/min/1.73 m2 . IRF patients had more severe heart failure reflected by lower admission eGFR, higher blood urea nitrogen, lower systolic blood pressure, lower sodium, and higher use of inotropes. IRF patients had higher 1-year mortality (25%) than non-IRF patients (15%) (P < 0.01). However, this relationship differed by BNP trajectory (P-interaction = 0.03). When stratified by BNP change, non-IRF patients and IRF patients with decreasing BNP had lower 1-year mortality than either non-IRF and IRF patients without decreasing BNP. However, in multivariate analysis, IRF was not associated with mortality [adjusted hazard ratio (HR) 1.0, 95% confidence interval (CI) 0.7-1.5] while BNP was (adjusted HR 0.5, 95% CI 0.3-0.7). When IRF was evaluated as transiently occurring or persisting at discharge, again only BNP change was significantly associated with mortality.

Conclusion: Improving renal function is associated with mortality in AHF but not independent of other variables and congestion status. Achieving adequate decongestion, as reflected by lower BNP, in AHF is more strongly associated with mortality than IRF.

Keywords: Acute heart failure; B-type natriuretic peptide; Congestion; Kidney function; Prognosis.

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Conflict of interest statement

Conflict of interest: J.H.I.: Investigator initiated research study from Baxter International, DSMB member for Sanifit Pharmaceuticals, Advisory Board member for AstraZeneca and Alpha Young. C.M. has received research support and speaker/consulting honoraria from several biomarkers companies but none directly related to this work. G.F. has no relevant disclosures directly related to the submitted manuscript; separate from submitted work, he is a trial member for Medtronic, Vifor, Boehringer Ingelheim, Bayer, Servier, Amgen and Novartis; he receives lecture fees from Servier, Novartis, and Boehringer Ingelheim. R.N. received grant funding from Abbott and Alere that ended in 2015. R.B. has received prior grant funding from Alere and current grant funding from Abbott; separate from this submitted work he always receives grant funding from Siemens and Lumos Diagnostics. P.T. has no disclosures directly related to the work submitted; she receives grant funding from the National Institutes of Health, Department of Homeland Security, and American Heart Association for unrelated research; she also receives consultant fees from Amgen, Novo-Nordisk, Esperion Therapeutics, Boehringer Ingelheim, and Sanofi. A.M. previously received grant funding from Abbott Laboratories and Alere Inc.; currently, he is a co-founder of Brainstorm Medical. P.T.M. previously received research funding from Abbott Laboratories and Alere Inc.; he currently received educational grant funding from Abbott; he also currently receives consulting fees from FAST biomedical. All other authors have nothing to disclose.

Figures

Figure 1
Figure 1
Unadjusted risk of 1-year mortality by the ratio of highest estimated glomerular filtration rate (eGFR) achieved during hospitalization to admission eGFR. Risk of mortality increased steeply with small improvements in eGFR; however, when eGFR improved ≥40% from admission eGFR, risk did not seem to increase more than the risk at 40% improvement. This is likely because few patients achieved an improvement in eGFR ≥40%.
Figure 2
Figure 2
Survival curves for 1-year mortality for improving renal function (IRF) vs. non-IRF (A) and when IRF and non-IRF are further stratified by the presence or absence of a decreasing B-type natriuretic peptide (BNP) trajectory (B). Patients with IRF had worse 1-year survival than non-IRF patients (A). The presence or absence of a decreasing BNP trajectory further risk stratified IRF and non-IRF patients (B). Those patients achieving successful decongestion, as defined by a trajectory of decreasing BNP ≥40% from admission value, had improved survival compared to patients not achieving a decreasing BNP regardless of changes in renal function.
Figure 3
Figure 3
Adjusted risk of 1-year mortality by the ratio of last B-type natriuretic peptide (BNP) measured to admission BNP in multivariable model 1 (A) and model 2 (B). The greater the trajectory of decrease in BNP, the lower the risk of death.
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