Hyponatremia in Heart Failure: Revisiting Pathophysiology and Therapeutic Strategies

Abstract

Hyponatremia is frequently encountered in patients with heart failure (HF), and its association with adverse outcomes is well-established in this population. While hyponatremia is an independent marker for severity of HF, it is not certain whether it has a causal impact on the progression of the disease. There are no universally accepted consensus guidelines regarding therapeutic strategies for HF-associated hyponatremia and volume overload; current societal guidelines do not address management of this complication. Whereas thiazide diuretics are known to induce or worsen hyponatremia in this setting through a number of mechanisms, loop diuretics can be considered a readily available first-line pharmacologic therapy. Consistent with pathophysiology of the disease and mechanisms of action of loop diuretics, available clinical evidence supports such an approach provided that patients can be closely monitored. Use of vasopressin receptor antagonists is an emerging therapeutic strategy in this setting, and the efficacy of these agents has so far been shown in a number of clinical studies. These agents can be reserved for patients with HF in whom initial appropriate loop diuretic therapy fails to improve serum sodium levels. Scope of the ProblemHyponatremia, the most common electrolyte abnormality in hospitalized patients, is associated with increasing morbidity and mortality in various clinical settings, including heart failure (HF). In an analysis of the Organized Program To Initiate Life-Saving Treatment In Hospitalized Patients With Heart Failure (OPTIMIZE-HF) study comprising data on 47 647 admissions for acute decompensated HF (ADHF), 19.7% of the patients presented with hyponatremia, defined as a serum sodium (Na) level <135 mEq/L.1 This subgroup of patients demonstrated significantly worse outcomes and was more likely to require dialysis and inotropic agents. The in-hospital mortality rate was also significantly higher compared with those patients with normal serum Na levels (6% vs 3.2%, P < 0.0001). Nearly half of the study population had preserved left ventricular ejection fraction (LVEF), suggestingthat presence of hyponatremiais an independent predictor of outcomes in HF patients with both preserved as well as reduced LVEF, a concept that has been confirmed by other authors. 2,3 In another study on more than 4000 patients, Lee et al demonstrated that chronic hyponatremia (defined as serum Na level <136 mEq/L) increased the 30-day mortality by 53% and the 1-year mortality by 46% in patients admitted with a primary diagnosis of HF. 4 In addition to its impact on survival, in a study on patients withThe author is a consultant for Otsuka America Pharmaceutical, Inc. The author has no other funding, financial relationships, or conflicts of interest to disclose. a discharge diagnosis of HF in 49 US academic medical centers, hyponatremia was shown to significantly increase the hospital length of stay. 5 HF being the most common reason for hospitalization in patients age >65 years, and with an annual cost exceedi...

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