Hyponatremia in patients with heart failure
- Richard H Sterns, MD
Richard H Sterns, MD
- Section Editor — Fluid and Electrolytes
- Professor of Medicine
- University of Rochester School of Medicine and Dentistry
- Stephen S Gottlieb, MD
Stephen S Gottlieb, MD
- Section Editor — Heart Failure
- Professor of Medicine
- University of Maryland School of Medicine
Hyponatremia can develop in patients with severe myocardial dysfunction. Issues related to hyponatremia in heart failure will be reviewed here. An overview of the treatment of hyponatremia is presented separately. (See "Overview of the treatment of hyponatremia in adults".)
Like most other causes of hyponatremia, heart failure impairs the ability to excrete ingested water by increasing antidiuretic hormone levels. When cardiac output and systemic blood pressure are reduced, "hypovolemic" hormones, such as renin (with a subsequent increase in angiotensin II formation), antidiuretic hormone (ADH), and norepinephrine, respond [1-3]. Although edematous patients with heart failure have increased plasma and extracellular fluid volumes, the body perceives volume depletion (reduced effective arterial blood volume) since the low cardiac output decreases the pressure perfusing the baroreceptors in the carotid sinus and the renal afferent arteriole.
The degree of neurohumoral activation is generally related to the severity of cardiac dysfunction, as assessed by left ventricular ejection fraction or functional class . The neurohumoral changes limit both sodium and water excretion in an attempt to return perfusion pressure to normal. ADH release directly enhances water reabsorption in the collecting tubules, whereas angiotensin II and norepinephrine limit distal water delivery (and thereby water excretion) by lowering the glomerular filtration rate (due to a marked reduction in renal perfusion) and by increasing proximal sodium and water reabsorption. In addition, both the low cardiac output and high angiotensin II levels are potent stimuli to thirst, leading to enhanced water intake.
PREDICTOR OF ADVERSE PROGNOSIS
Both antidiuretic hormone (ADH) release and the associated reduction in the serum sodium concentration parallel the severity of the heart failure . This relationship has prognostic importance since patient survival is significantly reduced (in comparison to normonatremic patients) once the serum sodium concentration falls below 137 meq/L (figure 1), and even mild hyponatremia is associated with an adverse prognosis following an acute myocardial infarction [4,5]. A similar inverse correlation exists between patient survival and the degree of elevation in serum norepinephrine levels (figure 2). (See "Predictors of survival in heart failure due to systolic dysfunction", section on 'Neurohumoral activation and heart rate'.)
Patients whose serum sodium levels fall below 125 meq/L solely as a result of heart failure usually have near end-stage disease. Patients with heart failure who have this severity of hyponatremia also frequently have hyperkalemia. Distal sodium and water delivery are so low in advanced cardiac disease that potassium excretion (primarily dependent upon distal potassium secretion) falls below the level of intake.
- 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; 128:564.
- Benedict CR, Johnstone DE, Weiner DH, et al. Relation of neurohumoral activation to clinical variables and degree of ventricular dysfunction: a report from the Registry of Studies of Left Ventricular Dysfunction. SOLVD Investigators. J Am Coll Cardiol 1994; 23:1410.
- Dzau VJ, Packer M, Lilly LS, et al. Prostaglandins in severe congestive heart failure. Relation to activation of the renin--angiotensin system and hyponatremia. N Engl J Med 1984; 310:347.
- 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; 73:257.
- Goldberg A, Hammerman H, Petcherski S, et al. Hyponatremia and long-term mortality in survivors of acute ST-elevation myocardial infarction. Arch Intern Med 2006; 166:781.
- 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; 111:2454.
- Gheorghiade M, Abraham WT, Albert NM, et al. Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J 2007; 28:980.
- Sato N, Gheorghiade M, Kajimoto K, et al. Hyponatremia and in-hospital mortality in patients admitted for heart failure (from the ATTEND registry). Am J Cardiol 2013; 111:1019.
- Schrier RW, Gross P, Gheorghiade M, et al. Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med 2006; 355:2099.
- Renneboog B, Musch W, Vandemergel X, et al. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 2006; 119:71.e1.
- Dzau VJ, Hollenberg NK. Renal response to captopril in severe heart failure: role of furosemide in natriuresis and reversal of hyponatremia. Ann Intern Med 1984; 100:777.
- Riegger GA, Kochsiek K. Vasopressin, renin and norepinephrine levels before and after captopril administration in patients with congestive heart failure due to idiopathic dilated cardiomyopathy. Am J Cardiol 1986; 58:300.
- Rouse D, Dalmeida W, Williamson FC, Suki WN. Captopril inhibits the hydroosmotic effect of ADH in the cortical collecting tubule. Kidney Int 1987; 32:845.
- Greenberg A, Verbalis JG. Vasopressin receptor antagonists. Kidney Int 2006; 69:2124.
- Verbalis JG, Goldsmith SR, Greenberg A, et al. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med 2007; 120:S1.
- Samsca (Tolvaptan): Drug Safety Communication - FDA Limits Duration and Usage Due To Possible Liver Injury Leading to Organ Transplant or Death. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm350185.htm (Accessed on May 20, 2013).
- Udelson JE, Smith WB, Hendrix GH, 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; 104:2417.
- Konstam MA, Gheorghiade M, Burnett JC Jr, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA 2007; 297:1319.
- Gheorghiade M, Niazi I, Ouyang J, et al. Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial. Circulation 2003; 107:2690.
- Patra S, Kumar B, Harlalka KK, et al. Short term efficacy and safety of low dose tolvaptan in patients with acute decompensated heart failure with hyponatremia: a prospective observational pilot study from a single center in South India. Heart Views 2014; 15:1.
- Berl T, Quittnat-Pelletier F, Verbalis JG, et al. Oral tolvaptan is safe and effective in chronic hyponatremia. J Am Soc Nephrol 2010; 21:705.
- Higashihara E, Torres VE, Chapman AB, et al. Tolvaptan in autosomal dominant polycystic kidney disease: three years' experience. Clin J Am Soc Nephrol 2011; 6:2499.
- Torres VE, Chapman AB, Devuyst O, et al. Tolvaptan in patients with autosomal dominant polycystic kidney disease. N Engl J Med 2012; 367:2407.