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CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction

      Abstract

      Background

      The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation.

      Methods

      This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively.

      Results

      The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391).

      Conclusion

      A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.

      Keywords

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      References

        • Ponikowski P
        • Voors AA
        • Anker SD
        • et al.
        2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
        Eur Heart J. 2016; 37: 2129-2200https://doi.org/10.1093/eurheartj/ehw128
        • Felker GM
        • Lee KL
        • Bull DA
        • et al.
        Diuretic strategies in patients with acute decompensated heart failure.
        N Engl J Med. 2011; 364: 797-805https://doi.org/10.1056/NEJMoa1005419
        • Núñez J
        • Miñana G
        • Santas E
        • Bertomeu-González V
        Cardiorenal syndrome in acute heart failure: revisiting paradigms.
        Rev Esp Cardiol. 2015; 68: 426-435https://doi.org/10.1016/j.rec.2014.10.016
        • Damman K
        • Valente MA
        • Voors AA
        • et al.
        Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis.
        Eur Heart J. 2014; 35: 455-469https://doi.org/10.1093/eurheartj/eht386
        • Núñez J
        • Núñez E
        • Miñana G
        • Bayés-Genis A
        • Sanchis J
        Worsening renal function in acute decompensated heart failure: the puzzle is still incomplete.
        JACC Heart Fail. 2016; 4: 232-233https://doi.org/10.1016/j.jchf.2015.10.013
        • Núñez J
        • Garcia S
        • Núñez E
        • et al.
        Early serum creatinine changes and outcomes in patients admitted for acute heart failure: the cardio-renal syndrome revisited.
        Eur Heart J Acute Cardiovasc Care. 2017; 6: 430-440https://doi.org/10.1177/2048872614540094
        • Mullens W
        • Abrahams Z
        • Francis GS
        • et al.
        Importance of venous congestion for worsening of renal function in advanced decompensated heart failure.
        J Am Coll Cardiol. 2009; 53: 589-596https://doi.org/10.1016/j.jacc.2008.05.068
        • Tuy T
        • Peacock 4th, WF
        Fluid overload assessment and management in heart failure patients.
        Semin Nephrol. 2012; 32: 112-120https://doi.org/10.1016/j.semnephrol.2011.11.014
        • Núñez J
        • Miñana G
        • Núñez E
        • et al.
        Clinical utility of antigen carbohydrate 125 in heart failure.
        Heart Fail Rev. 2014; 19: 575-584https://doi.org/10.1007/s10741-013-9402-y
        • Núñez J
        • Llàcer P
        • Bertomeu-González V
        • et al.
        Carbohydrate antigen-125-guided therapy in acute heart failure: CHANCE-HF: a randomized study.
        JACC Heart Fail. 2016; 4: 833-843https://doi.org/10.1016/j.jchf.2016.06.007
        • Núñez J
        • Llàcer P
        • Núñez E
        • et al.
        Antigen carbohydrate 125 and creatinine on admission for prediction of renal function response following loop diuretic administration in acute heart failure.
        Int J Cardiol. 2014; 174: 516-523https://doi.org/10.1016/j.ijcard.2014.04.113
        • García-Blas S
        • Bonanad C
        • Llàcer P
        • et al.
        diuretic strategies in acute heart failure and renal dysfunction: conventional vs carbohydrate antigen 125-guided strategy. clinical trial design.
        Rev Esp Cardiol (Engl Ed). 2017; 70: 1067-1073https://doi.org/10.1016/j.rec.2017.02.028
        • Levy WC
        • Mozaffarian D
        • Linker DT
        • et al.
        The Seattle Heart Failure Model: prediction of survival in heart failure.
        Circulation. 2006; 113: 1424-1433https://doi.org/10.1161/CIRCULATIONAHA.105.584102
        • 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: 803-869https://doi.org/10.1093/eurjhf/hfs105
        • Costanzo MR
        Verdict in: congestion guilty!.
        JACC Heart Fail. 2015; 3: 762-764https://doi.org/10.1016/j.jchf.2015.06.004
        • Miller WL
        • Mullan BP.
        Understanding the heterogeneity in volume overload and fluid distribution in decompensated heart failure is key to optimal volume management: role for blood volume quantitation.
        JACC Heart Fail. 2014; 2: 298-305https://doi.org/10.1016/j.jchf.2014.02.007
        • Gheorghiade M
        • Follath F
        • Ponikowski P
        • et al.
        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
        • Núñez J
        • Sanchis J
        • Bodí V
        • et al.
        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
        • Núñez J
        • Núñez E
        • Bayés-Genís A
        • et al.
        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
        • Núñez J
        • Núñez E
        • Sanchis J
        • et al.
        Antigen carbohydrate 125 and brain natriuretic peptide serial measurements for risk stratification following an episode of acute heart failure.
        Int J Cardiol. 2012; 159: 21-28https://doi.org/10.1016/j.ijcard.2011.02.001
        • Brisco MA
        • Zile MR
        • Hanberg JS
        • et al.
        Relevance of changes in serum creatinine during a heart failure trial of decongestive strategies: insights from the DOSE trial.
        J Card Fail. 2016; 22: 753-760https://doi.org/10.1016/j.cardfail.2016.06.423
        • Ahmad T
        • Jackson K
        • Rao VS
        • et al.
        Worsening renal function in acute heart failure patients undergoing aggressive diuresis is not associated with tubular injury.
        Circulation. 2018; 137: 2016-2028https://doi.org/10.1161/CIRCULATIONAHA.117.030112
        • Núñez J
        • Llàcer P
        • Núñez E
        • et al.
        Antigen carbohydrate 125 and creatinine on admission for prediction of renal function response following loop diuretic administration in acute heart failure.
        Int J Cardiol. 2014; 174: 516-523https://doi.org/10.1016/j.ijcard.2014.04.113
        • Damman K
        • van Deursen VM
        • Navis G
        • et al.
        Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease.
        J Am Coll Cardiol. 2009; 53: 582-588https://doi.org/10.1016/j.jacc.2008.08.080
        • Hanberg JS
        • Sury K
        • Wilson FP
        • et al.
        Reduced cardiac index is not the dominant driver of renal dysfunction in heart failure.
        J Am Coll Cardiol. 2016; 67: 2199-2208https://doi.org/10.1016/j.jacc.2016.02.058
        • Butler J
        • Anstrom KJ
        • Felker GM
        • et al.
        Efficacy and safety of spironolactone in acute heart failure: The ATHENA-HF randomized clinical trial.
        JAMA Cardiol. 2017; 2: 950-958https://doi.org/10.1001/jamacardio.2017.2198
        • Konstam MA
        • Kiernan M
        • Chandler A
        • et al.
        Short-term effects of tolvaptan in patients with acute heart failure and volume overload.
        J Am Coll Cardiol. 2017; 69: 1409-1419https://doi.org/10.1016/j.jacc.2016.12.035
        • Stienen S
        • Salah K
        • Moons AH
        • et al.
        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