Implications of worsening renal function before hospitalization for acute heart failure

Nicholas Wettersten^{1

2}, Stephen Duff³, Yu Horiuchi⁴, Dirk J van Veldhuisen⁵, Christian Mueller⁶, Gerasimos Filippatos⁷, Richard Nowak⁸, Christopher Hogan⁹, Michael C Kontos¹⁰, Chad M Cannon¹¹, Gerhard A Müeller¹², Robert Birkhahn¹³, Pam Taub², Gary M Vilke¹⁴, Kenneth McDonald^{15

16}, Niall Mahon¹⁶, Julio Nuñez^{17

18}, Carlo Briguori¹⁹, Claudio Passino²⁰, Alan Maisel², Patrick T Murray³, Joachim H Ix²¹

Affiliations

¹ Division of Cardiovascular Medicine, San Diego Veterans Affairs Medical Center, San Diego, California, USA.
² Division of Cardiovascular Medicine, University of California, San Diego, La Jolla, California, USA.
³ School of Medicine, University College Dublin, Dublin, Ireland.
⁴ Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan.
⁵ Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁷ Department of Cardiology, Athens University Hospital Attikon, University of Athens, Athens, Greece.
⁸ Department of Emergency Medicine, Henry Ford Hospital System, Detroit, Michigan, USA.
⁹ Division of Emergency Medicine and Acute Care Surgical Services, VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁰ Division of Cardiology, VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia, USA.
¹¹ Department of Emergency Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
¹² Department of Nephrology and Rheumatology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
¹³ Department of Emergency Medicine, New York Methodist, Brooklyn, New York, USA.
¹⁴ Department of Emergency Medicine, University of California, San Diego, La Jolla, California, USA.
¹⁵ Department of Cardiology, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
¹⁶ Department of Cardiology, St. Vincent's University Hospital, Dublin, Ireland.
¹⁷ Department of Cardiology, Hospital Clínico Universitario Valencia, INCLIVA, University of Valencia, Valencia, Spain.
¹⁸ CIBER in Cardiovascular Diseases, Madrid, Spain.
¹⁹ Department of Cardiology, Interventional Cardiology, Mediterranea Cardiocentro, Naples, Italy.
²⁰ Department of Cardiology and Cardiovascular Medicine, Fondazione Gabriele Monasterio, Pisa, Italy.
²¹ Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, La Jolla, California, USA.

PMID: 36325747
PMCID: PMC9871662
DOI: 10.1002/ehf2.14221

Implications of worsening renal function before hospitalization for acute heart failure

Nicholas Wettersten et al. ESC Heart Fail. 2023 Feb.

. 2023 Feb;10(1):532-541.

doi: 10.1002/ehf2.14221. Epub 2022 Nov 3.

Authors

Affiliations

¹ Division of Cardiovascular Medicine, San Diego Veterans Affairs Medical Center, San Diego, California, USA.
² Division of Cardiovascular Medicine, University of California, San Diego, La Jolla, California, USA.
³ School of Medicine, University College Dublin, Dublin, Ireland.
⁴ Division of Cardiology, Mitsui Memorial Hospital, Tokyo, Japan.
⁵ Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
⁶ Department of Cardiology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁷ Department of Cardiology, Athens University Hospital Attikon, University of Athens, Athens, Greece.
⁸ Department of Emergency Medicine, Henry Ford Hospital System, Detroit, Michigan, USA.
⁹ Division of Emergency Medicine and Acute Care Surgical Services, VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁰ Division of Cardiology, VCU Medical Center, Virginia Commonwealth University, Richmond, Virginia, USA.
¹¹ Department of Emergency Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
¹² Department of Nephrology and Rheumatology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.
¹³ Department of Emergency Medicine, New York Methodist, Brooklyn, New York, USA.
¹⁴ Department of Emergency Medicine, University of California, San Diego, La Jolla, California, USA.
¹⁵ Department of Cardiology, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland.
¹⁶ Department of Cardiology, St. Vincent's University Hospital, Dublin, Ireland.
¹⁷ Department of Cardiology, Hospital Clínico Universitario Valencia, INCLIVA, University of Valencia, Valencia, Spain.
¹⁸ CIBER in Cardiovascular Diseases, Madrid, Spain.
¹⁹ Department of Cardiology, Interventional Cardiology, Mediterranea Cardiocentro, Naples, Italy.
²⁰ Department of Cardiology and Cardiovascular Medicine, Fondazione Gabriele Monasterio, Pisa, Italy.
²¹ Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, La Jolla, California, USA.

PMID: 36325747
PMCID: PMC9871662
DOI: 10.1002/ehf2.14221

Abstract

Aims: Kidney function changes dynamically during AHF treatment, but risk factors for and consequences of worsening renal function (WRF) at hospital admission are uncertain. We aimed to determine the significance of WRF at admission for acute heart failure (AHF).

Methods and results: We evaluated a subgroup of 406 patients from The Acute Kidney Injury Neutrophil gelatinase-associated lipocalin Evaluation of Symptomatic heart failure Study (AKINESIS) who had serum creatinine measurements available within 3 months before and at the time of admission. Admission WRF was primarily defined as a 0.3 mg/dL or 50% creatinine increase from preadmission. Alternative definitions evaluated were a ≥0.5 mg/dL creatinine increase, ≥25% glomerular filtration rate decrease, and an overall change in creatinine. Predictors of admission WRF were evaluated. Outcomes evaluated were length of hospitalization, a composite of adverse in-hospital events, and the composite of death or HF readmission at 30, 90, and 365 days. Biomarkers' prognostic ability for these outcomes were evaluated in patients with admission WRF. One-hundred six patients (26%) had admission WRF. These patients had features of more severe AHF with lower blood pressure, higher BUN, and lower serum sodium concentrations at admission. Higher BNP (odds ratio [OR] per doubling 1.16-1.28, 95% confidence interval [CI] 1.00-1.55) and lower diastolic blood pressure (OR 0.97-0.98, 95% CI 0.96-0.99) were associated with a higher odds for the three definitions of admission WRF. The primary WRF definition was not associated with a longer hospitalization, but alternative WRF definitions were (1.3 to 1.6 days longer, 95% CI 1.0-2.2). WRF across definitions was not associated with a higher odds of adverse in-hospital events or a higher risk of death or HF readmission. In the subset of patients with WRF, biomarkers were not prognostic for any outcome.

Conclusions: Admission WRF is common in AHF patients and is associated with an increased length of hospitalization, but not adverse in-hospital events, death, or HF readmission. Among those with admission WRF, biomarkers did not risk stratify for adverse events.

Keywords: Acute heart failure; Acute kidney injury; Biomarkers; Cardiorenal syndrome.

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Conflict of interest statement

All study sites received funding from the study sponsors during the original conduct of the AKINESIS study. No direct funding was provided by the study sponsor for this analysis. Nicholas Wettersten: none declared. Yu Horiuchi: none declared. Dirk J. van Veldhuisen: none declared. Stephen Duff: none declared. Christian Mueller has received research support and speaker/consulting honoraria from several biomarkers companies but none directly related to this work. Gerasimos Filippatos has no relevant disclosures directly related to the submitted manuscript. Separate from submitted work, Dr. Filippatos is a trial member for Medtronic, Vifor, Boehringer Ingelheim, Bayer, Servier, Amgen and Novartis. He receives lecture fees from Servier, Novartis, and Boehringer Ingelheim. Richard Nowak: Received grant funding from Abbott and Alere that ended in 2015. Christopher Hogan: none declared. Michael C. Kontos: none declared. Chad M. Cannon: none declared. Gerhard A. Müller: none declared. Robert Birkhahn has received prior grant funding from Alere and current grant funding from Abbott. Separate from this submitted work he receives grant funding from Siemens. Pam Taub 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, Novartis, Medtronic, Amarin, Esperion Therapeutics, Bohringer‐Ingelheim, and Sanofi. Gary M. Vilke: none declared. Kenneth McDonald: none declared. Niall Mahon: none declared. Julio Nuñez has no disclosures directly related to the work submitted. He has received speaker fees from Novartis, Vifor Pharma, Boehringer Ingelheim, Astra Zeneca, Rovi, and Novo nordisk. Carlo Briguori: none declared. Claudio Passino: none declared. Alan Maisel previously received grant funding from Abbott Laboratories and Alere Inc. Currently, he is a co‐founder of Brainstorm Medical. Patrick T. Murray 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. Joachim Ix has grant support from Baxter International. He is on advisory boards for Akebia, AstraZeneka, Ardelyx, Alpha Young and Bayer. He serves on a Data and Safety Monitoring Board from Sanifit International.

Figures

**Figure 1**
Association between admission worsening renal definitions and length of stay and adverse in‐hospital events in the fully adjusted multivariable model. All definitions of admission worsening renal function except the primary definition were associated with an increased length of stay in the fully adjusted model (A). None of the definitions of admission worsening renal function were associated with a higher odds of adverse in‐hospital events in the fully adjusted model (B).

**Figure 2**
Kaplan–Meier plots for death or heart failure readmission at 1 year by presence or absence of admission worsening renal function. Patients with admission worsening renal function (WRF) did not have significantly different (P = 0.55) rates of death or heart failure readmission at 1 year.

See this image and copyright information in PMC

References

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Implications of worsening renal function before hospitalization for acute heart failure

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Implications of worsening renal function before hospitalization for acute heart failure

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