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Hyponatremia and outcomes in patients with heart failure
  1. Steven R Goldsmith
  1. Correspondence to Dr Steven R Goldsmith, Department of Cardiology, Hennepin County Medical Center, 701 Park Avenue, Minneapolis, MN 55415, USA;{at}

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Studies spanning several decades have identified hyponatremia as common and significantly associated with poor outcomes in patients with acutely decompensated heart failure (ADHF). Despite the development and wide application of neurohormonal inhibitory therapy, which might have been expected to reduce the incidence of hyponatremia, recent studies from both randomised controlled trials and registries continue to identify hyponatremia in up to 27% of patients with ADHF. Also, despite the use of contemporary therapies, hyponatremia remains independently and closely correlated with poor outcomes, including death.1 A key question which is unresolved is whether hyponatremia contributes directly to poor outcomes in ADHF or is simply a marker for disease severity or, possibly, for other factors which might influence disease progression.

Hyponatremia could, in theory, directly influence morbidity and mortality in HF. The brain undergoes adaptation to a slow fall in serum osmolality by losing osmotically active substances, including various neurotransmitters. This loss may lead to adverse effects on neurocognitive function.2 Whether myocytes, particularly dysfunctional myocytes, are affected by hypotonicity has never been studied. It is certainly possible that either mechanical or electrical function could be adversely affected.

Hyponatremia in heart failure is largely due to the inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). Free water reabsorption is mediated by the renal V2 receptor for AVP. However, the V1a effects of AVP include vasoconstriction and myocardial hypertrophy mediated by signalling pathways similar to those stimulated by angiotensin II. In theory, high AVP levels could adversely affect outcome in heart failure via V1a signalling.3 If this were true, hyponatremia may be a marker for high AVP levels, which in turn could affect outcome via excessive V1a stimulation.

Hyponatremia is often exacerbated by loop diuretic therapy, and clinicians often reduce diuretics when hyponatremia occurs, potentially leaving patients in a congested state. …

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  • Competing interests The author has received consulting income, research support and speaking fees from both Astellas and Otsuka, which manufacture Conivaptan and Tolvaptan respectively.

  • Provenance and peer review Commissioned; internally peer reviewed.