Hyponatremia in Heart Failure and Ventricular Assist Device Patients

  • Jason CobbEmail author
  • James L. Bailey


Hyponatremia is commonly seen in heart failure (HF) patients and is a poor prognostic marker of HF mortality. The more severe the hyponatremia, the greater the association with poor outcomes. Although hyponatremia can be caused by multiple mechanisms, in HF patients the hyponatremia is most commonly categorized as hypo-osmolal hyponatremia with hypervolemia. The pathogenesis of hyponatremia in HF is due to cardiac dysfunction which results in a reduced glomerular filtration rate and an increase in vasopressin (ADH) secretion. Most HF patients with hyponatremia are asymptomatic and can be managed by limiting water intake and using diuretics. However if the plasma sodium level is <125 mEq/L or if symptoms of hyponatremia are present, then more active management of this electrolyte abnormality is necessary. Diuretics are the principal treatment for both hyponatremia and HF since they result in hypotonic fluid losses. Recently, selective and nonselective vasopressin antagonists have become available. However, despite demonstrated efficacy in producing a water diuresis and a correction of hyponatremia, vasopressin antagonists are not commonly used in HF patients. Vasopression antagonists have not been shown to affect mortality, have some potentially serious adverse reactions, and are costly.


Hyponatremia Electrolyte disorder Heart failure Hypo-osmolal hyponatremia Central pontine myelinolysis Osmotic demyelination Loop diuretics Vasopressin antagonists Renin–angiotensin–aldosterone blockade Antidiuretic hormone Edema 


  1. 1.
    Adrogue HJ, Madias NE. Hyponatremia. N Engl J Med. 2000;342(21):1581–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Bettari L, et al. Significance of hyponatremia in heart failure. Heart Fail Rev. 2012;17(1):17–26.CrossRefPubMedGoogle Scholar
  3. 3.
    Ellison DH, Berl T. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Rossi J, et al. Improvement in hyponatremia during hospitalization for worsening heart failure is associated with improved outcomes: insights from the Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Chronic Heart Failure (ACTIV in CHF) trial. Acute Card Care. 2007;9(2):82–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Scrutinio D, et al. Prognostic impact of comorbidities in hospitalized patients with acute exacerbation of chronic heart failure. Eur J Intern Med. 2016;34:63–7.CrossRefPubMedGoogle Scholar
  6. 6.
    Rose EA, et al. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med. 2001;345(20):1435–43.CrossRefPubMedGoogle Scholar
  7. 7.
    Miller LW, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357(9):885–96.CrossRefPubMedGoogle Scholar
  8. 8.
    Lietz K, et al. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection. Circulation. 2007;116(5):497–505.CrossRefPubMedGoogle Scholar
  9. 9.
    Slaughter MS, et al. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361(23):2241–51.CrossRefPubMedGoogle Scholar
  10. 10.
    Imamura T, et al. Low cardiac output stimulates vasopressin release in patients with stage D heart failure. Circ J. 2014;78(9):2259–67.CrossRefPubMedGoogle Scholar
  11. 11.
    Leier CV, Dei Cas L, Metra M. Clinical relevance and management of the major electrolyte abnormalities in congestive heart failure: hyponatremia, hypokalemia, and hypomagnesemia. Am Heart J. 1994;128(3):564–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Lee WH, Packer M. Prognostic importance of serum sodium concentration and its modification by converting-enzyme inhibition in patients with severe chronic heart failure. Circulation. 1986;73(2):257–67.CrossRefPubMedGoogle Scholar
  13. 13.
    Goldberg A, et al. Hyponatremia and long-term mortality in survivors of acute ST-elevation myocardial infarction. Arch Intern Med. 2006;166(7):781–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Klein L, et al. Lower serum sodium is associated with increased short-term mortality in hospitalized patients with worsening heart failure: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) study. Circulation. 2005;111(19):2454–60.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Rondon-Berrios H, Berl T. Mild chronic hyponatremia in the ambulatory setting: significance and management. Clin J Am Soc Nephrol. 2015;10(12):2268–78.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Verbalis JG, et al. Tolvaptan and neurocognitive function in mild to moderate chronic hyponatremia: a randomized trial (INSIGHT). Am J Kidney Dis. 2016;67(6):893–901.CrossRefPubMedGoogle Scholar
  17. 17.
    Howard C, Berl T. Disorders of water balance: hyponatremia & hypernatremia. In: Lerma EV, Berns JS, Nissenson AR, editors. CURRENT diagnosis & treatment: nephrology & hypertension. New York, NY: McGraw-Hill; 2009.Google Scholar
  18. 18.
    De Vecchis R, et al. Vasopressin receptor antagonists for the correction of hyponatremia in chronic heart failure: an underutilized therapeutic option in current clinical practice? J Clin Med. 2016;5(10).Google Scholar
  19. 19.
    Carpentier E, et al. Identification and characterization of an activating F229V substitution in the V2 vasopressin receptor in an infant with NSIAD. J Am Soc Nephrol. 2012;23(10):1635–40.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Esposito P, et al. The syndrome of inappropriate antidiuresis: pathophysiology, clinical management and new therapeutic options. Nephron Clin Pract. 2011;119(1):c62–73. discussion c73.CrossRefPubMedGoogle Scholar
  21. 21.
    Sica DA. Hyponatremia and heart failure—pathophysiology and implications. Congest Heart Fail. 2005;11(5):274–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Sterns RH. Disorders of plasma sodium—causes, consequences, and correction. N Engl J Med. 2015;372(1):55–65.CrossRefPubMedGoogle Scholar
  23. 23.
    Oren RM. Hyponatremia in congestive heart failure. Am J Cardiol. 2005;95(9A):2B–7B.CrossRefPubMedGoogle Scholar
  24. 24.
    Adrogue HJ, Madias NE. The challenge of hyponatremia. J Am Soc Nephrol. 2012;23(7):1140–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Sterns R, Gottlieb S. Hyponatremia in patients with heart failure. 2017.Google Scholar
  26. 26.
    Fujisawa H, et al. Chronic hyponatremia causes neurologic and psychologic impairments. J Am Soc Nephrol. 2016;27(3):766–80.CrossRefPubMedGoogle Scholar
  27. 27.
    Sterns RH, Hix JK, Silver S. Treating profound hyponatremia: a strategy for controlled correction. Am J Kidney Dis. 2010;56(4):774–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Verbalis JG, et al. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120(11 Suppl 1):S1–21.CrossRefPubMedGoogle Scholar
  29. 29.
    Sterns RH, Riggs JE, Schochet SS Jr. Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med. 1986;314(24):1535–42.CrossRefPubMedGoogle Scholar
  30. 30.
    Verbrugge FH, et al. Hyponatremia in acute decompensated heart failure: depletion versus dilution. J Am Coll Cardiol. 2015;65(5):480–92.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Felker GM, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797–805.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    De Vecchis R, Ciccarelli A, Pucciarelli A. Unloading therapy by intravenous diuretic in chronic heart failure: a double-edged weapon? J Cardiovasc Med (Hagerstown). 2010;11(8):571–4.Google Scholar
  33. 33.
    Rouse D, et al. Captopril inhibits the hydroosmotic effect of ADH in the cortical collecting tubule. Kidney Int. 1987;32(6):845–50.CrossRefPubMedGoogle Scholar
  34. 34.
    Danziger J, Zeidel ML. Osmotic homeostasis. Clin J Am Soc Nephrol. 2015;10(5):852–62.CrossRefPubMedGoogle Scholar
  35. 35.
    Udelson JE, et al. Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001;104(20):2417–23.CrossRefPubMedGoogle Scholar
  36. 36.
    Konstam MA, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297(12):1319–31.CrossRefPubMedGoogle Scholar
  37. 37.
    Schrier RW, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099–112.CrossRefPubMedGoogle Scholar
  38. 38.
    Berl T, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol. 2010;21(4):705–12.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Torres VE, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med. 2012;367(25):2407–18.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    FDA. FDA Drug Safety Communication: FDA limits duration and usage of Samsca (tolvaptan) due to possible liver injury leading to organ transplant or death.
  41. 41.
    Baur BP, Meaney CJ. Review of tolvaptan for autosomal dominant polycystic kidney disease. Pharmacotherapy. 2014;34(6):605–16.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Renal DivisionEmory University School of MedicineAtlantaUSA

Personalised recommendations