Moderate potassium lowering effect of exogenous atrial natriuretic peptide in patients with acute heart failure

Published:August 20, 2021DOI:


      • Exogenous atrial natriuretic peptide lowered potassium level in acute heart failure.
      • Changes in potassium were correlated with urine volume.
      • Risk of hypokalemia was low unless treated with additional furosemide.


      Background Recent data suggest that the angiotensin receptor neprilysin inhibitor modulates plasma levels of natriuretic peptides and attenuates the risk of hyperkalemia in patients with heart failure (HF). However, the impact of natriuretic peptides on serum electrolyte abnormalities, especially abnormalities in sodium and potassium levels in patients with HF remains unclear.
      Methods We performed a post-hoc analysis of a multicenter prospective cohort study in 162 patients with acute HF (74.2 ± 13.3 years, 64.2% male, left ventricular ejection fraction 44 ± 15%) treated with intravenous carperitide, an exogenous atrial natriuretic peptide.
      Results The dose of carperitide was correlated with urine volume (σ = 0.205, p = 0.009), suggesting a significant diuretic effect. During the initial 48 h, serum sodium level remained unchanged both in 53 patients with carperitide alone (from 140 ± 4 to 140 ± 3 mEq/L, p = 0.653) and 109 patients treated with a combination of carperitide and furosemide (141 ± 4 to 141 ± 4 mEq/L, p = 0.644). On the contrary, serum potassium level was decreased both in patients with carperitide alone (from 4.32 ± 0.70 to 4.08 ± 0.47 mEq/L, p = 0.004) and patients treated with a combination of carperitide and furosemide (4.17 ± 0.55 to 3.98 ± 0.47, p < 0.001), with a significant association between urine volume and change in potassium level in patients treated with carperitide alone (σ = -0.313, p = 0.023). The incidence of hypokalemia at 24 h was higher in patients treated with 20 mg furosemide or more (12.5% vs. 2.8%, p = 0.039).
      Conclusions Serum potassium level decreased after HF treatment with exogenous atrial natriuretic peptide, with a significant correlation to urine volume. The risk of hypokalemia was low, unless treated with additional furosemide.

      Graphical abstract


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        • Ponikowski P.
        • Voors A.A.
        • Anker S.D.
        • Bueno H.
        • Cleland J.G.F.
        • Coats A.J.S.
        • 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: 2129-2200
        • McMurray J.J.V.
        • Packer M.
        • Desai A.S.
        • Gong J.
        • Lefkowitz M.P.
        • Rizkala A.R.
        • et al.
        Angiotensin–neprilysin inhibition versus enalapril in heart failure.
        N Engl J Med. 2014; 371: 993-1004
        • Desai A.S.
        • Vardeny O.
        • Claggett B.
        • McMurray J.J.
        • Packer M.
        • Swedberg K.
        • et al.
        Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril: a secondary analysis of the PARADIGM-HF trial.
        JAMA Cardiol. 2017; 2: 79-85
        • Boerrigter G.
        • Lapp H.
        • Burnett JC.
        Modulation of cGMP in heart failure: a new therapeutic paradigm.
        Handb Exp Pharmacol. 2009; 191: 485-506
        • Ferreira J.P.
        • Butler J.
        • Rossignol P.
        • Pitt B.
        • Anker S.D.
        • Kosiborod M.
        • et al.
        Abnormalities of potassium in heart failure: JACC state-of-the-art review.
        J Am Coll Cardiol. 2020; 75: 2836-2850
        • Verbrugge F.H.
        • Steels P.
        • Grieten L.
        • Nijst P.
        • Tang W.H.
        • Mullens W.
        Hyponatremia in acute decompensated heart failure: depletion versus dilution.
        J Am Coll Cardiol. 2015; 65: 480-492
        • Hoss S.
        • Elizur Y.
        • Luria D.
        • Keren A.
        • Lotan C.
        • Gotsman I.
        Serum potassium levels and outcome in patients with chronic heart failure.
        Am J Cardiol. 2016; 118: 1868-1874
        • Núñez J.
        • Bayés-Genís A.
        • Zannad F.
        • Rossignol P.
        • Núñez E.
        • Bodí V.
        • et al.
        Long-term potassium monitoring and dynamics in heart failure and risk of mortality.
        Circulation. 2018; 137: 1320-1330
        • Aldahl M.
        • Jensen A.S.C.
        • Davidsen L.
        • Eriksen M.A.
        • Møller Hansen S.
        • Nielsen B.J.
        • et al.
        Associations of serum potassium levels with mortality in chronic heart failure patients.
        Eur Heart J. 2017; 38: 2890-2896
        • Matsumoto S.
        • Nakazawa G.
        • Ohno Y.
        • Ishihara M.
        • Sakai K.
        • Nakamura N.
        • et al.
        Efficacy of exogenous atrial natriuretic peptide in patients with heart failure with preserved ejection fraction: deficiency of atrial natriuretic peptide and replacement therapy.
        ESC Heart Fail. 2020; 7: 4172-4181
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • Butler J.
        • Casey D.E.
        • Drazner M.H.
        • et al.
        2013 ACCF/AHA guideline for the management of heart failure: a report of the American college of cardiology foundation/American heart association task force on practice guidelines.
        J Am Coll Cardiol. 2013; 62: e147-e239
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • Butler J.
        • Casey D.E.
        • Colvin M.M.
        • et al.
        2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American college of cardiology/American heart association task force on clinical practice guidelines and the heart failure society of America.
        J Card Fail. 2017; 23: 628-651
        • Hoorn E.J.
        • Zietse R.
        Diagnosis and treatment of hyponatremia: compilation of the guidelines.
        J Am Soc Nephrol. 2017; 28: 1340-1349
        • Richards A.M.
        • Ikram H.
        • Yandle T.G.
        • Nicholls M.G.
        • Webster M.W.I.
        • Espiner E.A.
        Renal, haemodynamic, and hormonal effects of human alpha atrial natriuretic peptide in healthy volunteers.
        Lancet. 1985; 325: 545-549
        • Saito Y.
        • Nakao K.
        • Nishimura K.
        • Sugawara A.
        • Okumura K.
        • Obata K.
        • et al.
        Clinical application of atrial natriuretic polypeptide in patients with congestive heart failure: beneficial effects on left ventricular function.
        Circulation. 1987; 76: 115-124
        • Wan S.H.
        • Stevens S.R.
        • Borlaug B.A.
        • Anstrom K.J.
        • Deswal A.
        • Felker G.M.
        • et al.
        Differential response to low-dose dopamine or low-dose nesiritide in acute heart failure with reduced or preserved ejection fraction.
        Circ Heart Fail. 2016; 9e002593
        • Hata N.
        • Seino Y.
        • Tsutamoto T.
        • Hiramitsu S.
        • Kaneko N.
        • Yoshikawa T.
        • et al.
        Effects of carperitide on the long-term prognosis of patients with acute decompensated chronic heart failure: the PROTECT multicenter randomized controlled study.
        Circ J. 2008; 72: 1787-1793
        • Ellison D.H.
        Clinical pharmacology in diuretic use.
        Clin J Am Soc Nephrol. 2019; 14: 1248-1257
        • Rocco S.
        • Opocher G.
        • Carpenè G.
        • Mantero F.
        Atrial natriuretic peptide infusion in primary aldosteronism. Renal, hemodynamic and hormonal effects.
        Am J Hypertens. 1990; 3: 668-673
        • Tanabe Y.
        • Okubo S.
        • Hoshino K.
        • Abe N.
        • Takahashi S.
        • Asano M.
        • et al.
        Protective effect of carperitide on aldosterone in congestive heart failure patients.
        J Card Fail. 2008; 14: S157-S158
        • Shiraishi Y.
        • Kohsaka S.
        • Sato N.
        • Takano T.
        • Kitai T.
        • Yoshikawa T.
        • et al.
        9-year trend in the management of acute heart failure in Japan: a report from the national consortium of acute heart failure registries.
        J Am Heart Assoc. 2018; 7e008687