Hyponatremia is one of the newer and emerging risk factors for an adverse prognosis in chronic heart failure. Why decreased serum sodium is associated with worse prognosis remains unclear. It may reflect worsening heart failure and the deleterious effects of activation of neurohormones. The mechanism of hyponatremia in heart failure also remains unclear. A relatively greater degree of free-water retention compared to sodium retention is probably the major mechanism. The treatment of significant hyponatremia in heart failure is difficult. The conventional treatments such as fluid restriction, infusion of hypertonic saline, and aggressive diuretic therapies are not usually effective. Vasopressin receptor antagonists have been shown to enhance aquaresis and correct hyponatremia. However, long-term beneficial effects of such treatments in chronic heart failure have not been documented.
Adrogue HJ, Madias NEHyponatremia. N Engl J Med. 2000; 342:1581-1589.
2.
Anderson RJ, Chung HM, Kluge R., Schrier RWHyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1985;102(2):164-168.
3.
Wong LL, Verbalis JGVasopressin V2 receptor antagonists. Cardiovascular Res. 2001;51(3):391-402.
4.
Oren RMHyponatremia in congestive heart failure. Am J Cardiol . 2005;95(suppl):2B-7B.
5.
Sica DAHyponatremia and heart failure-pathophysiology and implications. Congest Heart Fail. 2005;11(5):274-277.
6.
Rossi J., Bayram M., Udelson JE, 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):82-86.
7.
Klein L., O’Connor CM, Leimberger JD, 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):2454-2460.
8.
Gheorghiade M., Rossi JS, Cotts W., et al. Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE Trial. Arch Intern Med. 2007;167(18):1998-2005.
9.
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):257-267.
10.
Chin MH, Goldman L.Correlates of major complications or death in patients admitted to the hospital with congestive heart failure. Arch Intern Med . 1996;156:1814-1820.
11.
Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D., Tu JVPredicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA. 2003; 290(19):2581-2587.
12.
Schrier RW, Abraham WTHormones and hemodynamics in heart failure. N Engl J Med. 1999;341(8):577-585.
13.
Schuster VL , Kokko JP, Jacobson HR. Angiotensin II directly stimulates sodium transport in rabbit proximal convoluted tubules. J Clin Invest. 1984;73(2):507-515.
14.
Lilly LS, Dzau VJ, Williams GH, Rydstedt L., Hollenberg NKHyponatremia in congestive heart failure: implications for neuro-humoral activation and responses to orthostasis. J Clin Endocrinol Metab. 1984;59:924-993.
15.
Dzau VJ, Packer M., Lilly LS, Swartz SL, Hollenberg NK, Williams GHProstaglandins in severe congestive heart failure. Relation to activation of the renin-angiotensin system and hyponatremia. N Engl J Med. 1984;310(6):347-352.
16.
Leter CV, Del 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): 564-574.
17.
Goldsmith SR , Francis GS, Cowley AW Jr.Arginine vasopressin and the renal response to water loading in congestive heart failure. Am J Cardiol . 1986;58(3):295-299.
18.
Schrier RW, Berl T., Anderson RJOsmotic and nonosmotic control of vasopressin release. Am J Physiol. 1979;236(4):F321-F332.
19.
Greenberg A.Diuretic complications. Am J Med Sci. 2003;319(1): 10-24.
20.
Szatalowicz VL, Arnold PE, Chaimovitz C., Bichet D., Berl T., Schrier RWRadioimmunoassay of plasma arginine vasopressin in hyponatremic patients with congestive heart failure. N Engl J Med. 1981;305(5):263-266.
21.
Francis GS, Benedict C., Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation . 1990;82(5):1724-1729.
22.
Creager MA, Faxon DP, Cutler SS, Kohlmann O., Ryan TJ, Gavras H.Contribution of vasopressin to vasoconstriction in patients with congestive heart failure: comparison with the renin-angiotensin system and the sympathetic nervous system. J Am Coll Cardiol. 1986;7(4):758-765.
23.
Goldsmith SR , Francis GS, Cowley AW Jr, Goldenberg IF, Cohn JNHemodynamic effects of infused arginine vasopressin in congestive heart failure . J Am Coll Cardiol . 1986;8(4):779-783.
24.
Tanoue A., Ito S., Honda K., et al. The vasopressin 1b receptor critically regulates hypothalamic-pituitary-adrenal axis activity under both stress and resting conditions. J Clin Invest. 2004;113(2): 302-309.
25.
Nielsen S., Kwon TH, Christensen BM, Promeneur D., Frøkiaer J., Marples D.Physiology and pathophysiology of renal aquaporins. J Am Soc Nephrol. 1999;10(3):647-663.
26.
Udelson JE, Smith WB, Hedrix GH, et al. Acute hemodynamic effects of conivaptan, a dual V1a and V2 vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001;104(20):2417-2423.
27.
Gheorghiade M., Gattis WA, O’Connor CM, et al. Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized control trial. JAMA. 2004;291(16):1963-1971.
28.
Gheorghiade M., Konstam MA, Burnett JC Jr, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297(12):1332-1343.
29.
Goldsmith SR , Elkayam U., Haught WH, Barve A., He W.Efficacy and safety of the vasopressin V1A/V2-receptor antagonist conivaptan in acute decompensated heart failure: A dose-ranging pilot study. J Card Fail. 2008;14:641-647.
