Hyponatremia in Heart Failure | Ten Points to Remember

Verbrugge FH, Steels P, Grieten L, Nijst P, Tang WH, Mullens W.
Hyponatremia in Acute Decompensated Heart Failure: Depletion Versus Dilution. J Am Coll Cardiol 2015;65:480-492.

The following are 10 summary points to remember about this review article on hyponatremia in acute decompensated heart failure (ADHF):

  1. Hyponatremia (serum sodium <135 mEq/L) is present in about 20% of ADHF patients upon admission.
  2. The pathophysiology of hyponatremia in ADHF is more often dilutional rather than depletional (the latter is due to sodium wasting diuretics).
  3. Dilutional hyponatremia is due to impaired water excretion due to increased non-osmotic release of arginine vasopressin (AVP) and insufficient tubular flow through the diluting (distal) segments of the nephron.
  4. ADHF patients compared to healthy volunteers show a more pronounced increase in plasma AVP levels with osmotic loading and this osmotic release of AVP increases linearly with small changes in serum osmolality, whereas the non-osmotic AVP release is exponential. This exponential release of AVP results in high levels that have potent vasoconstrictor effects, which contribute to hemodynamic deterioration in ADHF.
  5. The combination of very low dietary sodium intake in HF and exaggerated losses due to diuretic therapy might lead to progressive depletion of whole-body sodium.
  6. Loop diuretics interfere with the renal capacity to concentrate urine resulting in less reabsorption of free water and in the production of hypotonic urine—therefore relative protection against hyponatremia. However, in profound volume depletion with strong neurohormonal activation and compromised renal blood flow, loop diuretics will fail to elicit meaningful diuresis. Eventually, this results in depressed glomerular filtration rate (GFR) and distal nephron flow, and in the presence of a strongly upregulated AVP—creating an environment for hyponatremia.
  7. It is prudent to avoid mineralocorticoid receptor antagonists (MRAs) until serum sodium levels are corrected because of their ability to interfere with sodium reabsorption—and instead better to utilize acetazolamide in such cases with volume overload and diuretic resistance.
  8. Management of hyponatremia in ADHF includes: a) first determine whether plasma hypotonicity is present and correct factors such as hyperglycemia when present; b) avoid thiazide diuretics, MRAs, and ENaC blockers such as amiloride and treat hypokalemia and hypomagnesmia; and c) differentiate between depletional hyponatremia requiring administration of saline versus dilutional hyponatremia where free water excretion should be promoted.
  9. Regarding acute treatment of dilutional hyponatremia: a) the addition of hypertonic saline to improve loop diuretic efficacy is controversial; b) acetazolamide should be preferred over thiazide diuretics, MRAs, and ENaC blockers; and c) AVP antagonists (tolvaptan, satavaptan, lixivaptan, and conivaptan) promote free water excretion by prevention of aquaporin-2 channel availability in the collecting ducts of the nephron—randomized clinical trials are needed to determine whether they improve survival in severe hyponatremia (<130 mmol/L).
  10. Regarding long-term management of hypotonic dilutional hyponatremia, potential treatments (since the value of following therapies remains insufficiently elucidated) include: a) water restriction, b) AVP antagonists, c) renin-angiotensin-system blockers since they increase renal blood flow and decrease proximal tubular sodium reabsorption, and d) inotropes and vasodilator therapies (including nitroprusside converted to oral hydralazine and nitrates, serelaxin) by increasing effective circulatory volume.

Keywords: Heart Failure, Amiloride, Diuretics, Sodium Chloride Symporter Inhibitors, Sodium Potassium Chloride Symporter Inhibitors, Hydralazine, Hypokalemia, Hyperglycemia, Hyponatremia, Mineralocorticoid Receptor Antagonists, Osmolar Concentration, Renal Circulation, Water, Vasoconstrictor Agents

< Back to Listings