Highlights
- •The optimal length of stay for acute heart failure (HF) hospitalization is uncertain.
- •Up to now, longer but also shorter stays are associated with an increased risk of HF readmission.
- •CA125 is a valuable biomarker for congestion, worse prognosis, and a valuable tool for guiding treatment in patients with HF.
- •Patients with CA125≥35 U/mL displayed higher rates of 6-month HF readmission.
- •LOS7 days shows a protective role in the risk of mid-term HF readmission in patients with high CA125 levels.
Abstract
Background
The optimal length of stay (LOS) in patients hospitalized for acute heart failure
(AHF) remains controversial. Plasma antigen carbohydrate 125 (CA125) has emerged as
a reliable proxy of congestion. We aimed to evaluate whether there is a differential
impact of LOS on the risk of 6-month AHF readmission across CA125 levels.
Methods
This is a retrospective study that included 1,387 patients discharged for AHF in two
third-level centers. CA125 was measured 48±24 h after admission. The association between
CA125 and LOS with the risk of subsequent AHF readmission at 6 months was analyzed
by Cox regression analysis accounting for death as a competing event.
Results
The median (IQR) age of the sample was 78 (69–83) years, 625 (41.1%) patients were
women, and 832 (60%) exhibited preserved left ventricular ejection fraction. The median
LOS and CA125 were 6 (4–9) days and 36 (17–83) U/mL, respectively. A total of 707
(51%) patients displayed high CA125 levels (≥35 U/mL). At 6 months, 87 deaths (6,3%)
and 304 AHF readmissions (21,9%) were registered, respectively. A multivariate analysis
revealed a differential effect of LOS on 6-month AHF readmission across CA125 levels
(p-value for interaction=0.010). In those with CA125<35 U/mL, LOS≥7 days did not modify
the risk (HR:1.31; 95% CI: 0.92-1.87, p=0.131). Conversely, in those with CA125≥35 U/mL, LOS≥7 days was associated with a
lower risk of AHF readmission (HR:0.70; 95% CI: 0.51-0.98, p=0.036).
Conclusions
In patients with AHF, high CA125 levels may identify those patients that benefit from
a more prolonged hospitalization in terms of reducing the risk of mid-term AHF readmissions.
Graphical abstract

Graphical Abstract
Keywords
Abbreviations:
AHF (acute heart failure), CA125 (antigen carbohydrate 125), CI (confidence interval), CRT (cardiac resynchronization therapy), ECG (electrocardiogram), HF (heart failure), HR (hazard ratios), ICD (implantable cardioverter-defibrillator), IQR (interquartile range), LOS (length of stay), LVEF (left ventricular ejection fraction), MUC16 (mucin 16), NT-proBNP (amino-terminal pro-brain natriuretic peptide), NYHA (New York Heart Association), SBP (systolic blood pressure)To read this article in full you will need to make a payment
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References
- Are we targeting the right metric for heart failure? Comparison of hospital 30-day readmission rates and total episode of care inpatient days.Am Heart J. 2013; 165: 987-994https://doi.org/10.1016/j.ahj.2013.02.006
- Relation of acute heart failure hospital length of stay to subsequent readmission and all-cause mortality.Am J Cardiol. 2015; 116: 400-405https://doi.org/10.1016/j.amjcard.2015.04.052
- Predictors and associations with outcomes of length of hospital stay in patients with acute heart failure: results from VERITAS.J Card Fail. 2016; 22: 815-822https://doi.org/10.1016/j.cardfail.2015.12.017
- Updates in heart failure 30-day readmission prevention.Heart Fail Rev. 2019; 24: 177-187https://doi.org/10.1016/j.cardfail.2015.12.017
- length of hospital stay and its impact on subsequent early readmission in patients with acute heart failure: a report from the WET-HF Registry.Heart Vessels. 2019; 34: 1777-1788https://doi.org/10.1007/s00380-019-01432-y
- length of stay and risk of very early readmission in acute heart failure.Eur J Intern Med. 2017; 42: 61-66https://doi.org/10.1016/j.ejim.2017.04.003
- Timing and causes of readmission after acute heart failure hospitalization—insights from the heart failure network trials.J Card Fail. 2016; 22: 875-883https://doi.org/10.1016/j.cardfail.2016.04.014
- Associations between short or long length of stay and 30-day readmission and mortality in hospitalized patients with heart failure.JACC Heart Fail. 2017; 5: 578-588https://doi.org/10.1016/j.jchf.2017.03.012
- Clinical role of CA125 in worsening heart failure.JACC Heart Fail. 2020; 8: 386-397https://doi.org/10.1016/j.jchf.2019.12.005
- improvement in risk stratification with the combination of the tumour marker antigen carbohydrate 125 and brain natriuretic peptide in patients with acute heart failure.Eur Heart J. 2010; 31: 1752-1763https://doi.org/10.1093/eurheartj/ehq142
- The emerging role of carbohydrate antigen 125 in heart failure.Biomark Med. 2020; 14: 249-252https://doi.org/10.2217/bmm-2019-0470
- Long-term serial kinetics of N-terminal pro B-type natriuretic peptide and carbohydrate antigen 125 for mortality risk prediction following acute heart failure.Eur Heart J Acute Cardiovasc Care. 2017; 6: 685-696https://doi.org/10.1177/2048872616649757
- Clinical utility of antigen carbohydrate 125 in heart failure.Heart Fail Rev. 2014; 19: 575-584https://doi.org/10.1007/s10741-013-9402-y
- Carbohydrate antigen 125 in heart failure. A new era in the monitoring and control of treatment.Med Clin. 2019; 152: 266-273https://doi.org/10.1016/j.medcli.2018.08.020
- Carbohydrate antigen-125 in heart failure.JACC Heart Fail. 2018; 6: 441-442https://doi.org/10.1016/j.jchf.2018.01.006
- CA125-guided diuretic treatment versus usual care in patients with acute heart failure and renal dysfunction.Am J Med. 2020; 133: 370-380.e4https://doi.org/10.1016/j.amjmed.2019.07.041
- Carbohydrate antigen-125–guided therapy in acute heart failure.JACC Heart Fail. 2016; 4: 833-843https://doi.org/10.1016/j.jchf.2016.06.007
- Congestion in heart failure: a contemporary look at physiology, diagnosis and treatment.Nat Rev Cardiol. 2020; 17: 641-655https://doi.org/10.1038/s41569-020-0379-7
- Early unplanned readmissions after admission to hospital with heart failure.Am J Cardiol. 2019; 124: 736-745https://doi.org/10.1016/j.amjcard.2020.12.008
- The dilemma, causes and approaches to avoid recurrent hospital readmissions for patients with chronic heart failure.Heart Fail Rev. 2012; 17: 345-353https://doi.org/10.1007/s10741-011-9256-0
- Acute decompensated heart failure (ADHF): a comprehensive contemporary review on preventing early readmissions and postdischarge death.Int J Cardiol. 2016; 223: 1035-1044https://doi.org/10.1016/j.ijcard.2016.07.259
- Do countries or hospitals with longer hospital stays for acute heart failure have lower readmission rates?: Findings from ASCEND-HF.Circ Heart Fail. 2013; 6: 727-732https://doi.org/10.1161/CIRCHEARTFAILURE.112.000265
- Trends in length of stay and short-term outcomes among Medicare patients hospitalized for heart failure, 1993-2006.JAMA. 2010; 303: 2141-2147https://doi.org/10.1001/jama.2010.748
- The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology.Eur J Heart Fail. 2019; 21: 137-155https://doi.org/10.1002/ejhf.1369
- Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine.Eur J Heart Fail. 2010; 12: 423-433https://doi.org/10.1093/eurjhf/hfq045
- A comprehensive, longitudinal description of the in-hospital and post-discharge clinical, laboratory, and neurohormonal course of patients with heart failure who die or are re-hospitalized within 90 days: analysis from the EVEREST trial.Heart Fail Rev. 2012; 17: 485-509https://doi.org/10.1007/s10741-011-9280-0
- NT-proBNP (N-Terminal pro-B-Type Natriuretic Peptide)-guided therapy in acute decompensated heart failure: PRIMA II randomized controlled trial (Can NT-ProBNP-guided therapy during hospital admission for acute decompensated heart failure reduce mortality and readmissions?).Circulation. 2018; 137: 1671-1683https://doi.org/10.1161/CIRCULATIONAHA.117.029882
- Rehospitalization for heart failure.J Am Coll Cardiol. 2013; 61: 391-403https://doi.org/10.1016/j.jacc.2012.09.038
- The degree of the predischarge pulmonary congestion in patients hospitalized for worsening heart failure predicts readmission and mortality.Cardiology. 2021; 146: 49-59https://doi.org/10.1159/000510073
- prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure.Int J Cardiol. 2018; 258: 185-191https://doi.org/10.1016/j.ijcard.2018.01.067
Article info
Publication history
Published online: June 12, 2021
Accepted:
May 21,
2021
Received in revised form:
May 20,
2021
Received:
February 23,
2021
Identification
Copyright
© 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.