Hyponatraemia is strongly associated with a higher risk of mortality in patients with acute or chronic heart failure.18,19 A patient whose hyponatraemia recovers to normal during an admission for heart failure has a better outcome than patients with persistent hyponatraemia at discharge.20
Salt restriction or salt supplementation?
Treatment of hyponatraemia in heart failure remains a controversial subject: in practice, many patients admitted with heart failure are placed on a fluid restriction in the hope that limiting oral free water intake, in conjunction with loop diuretics, will treat haemodilution. However, evidence to support this is scant and current guidelines recommend fluid restriction of 1.5–2.0 L/day for treatment of congestion rather than hyponatraemia – again, in the absence of any evidence this is the correct approach.21 Similarly, sodium restriction is often used, but without supporting evidence. A low salt diet is unpalatable, and just induces thirst rather than normalising sodium.22
There is some evidence that high sodium diets23 or sodium supplementation24,25 is the correct approach. Compared to high dose intravenous (IV) loop diuretic alone, IV hypertonic saline in conjunction with diuretic in patients admitted with heart failure and severe fluid retention may:
- improve diuresis (measured by reduction in body weight).24
- increase serum sodium levels.24
- cause a greater reduction in natriuretic peptide levels.25
- reduce length of hospital stay.25
- reduce readmission rate.25
The dose of diuretic used in these studies was far higher than recommended in guidelines (500–1,000 mg, twice daily) and it is possible that the ‘beneficial’ effect of hypertonic saline is merely protective against such high doses of loop diuretic. However, one small study (n=44, New York Heart Association [NYHA] class III-IV, median left ventricular ejection fraction [LVEF] 32%), found improvements in diuresis (measured by urine volume) and natriuretic peptide levels with 40 mg of furosemide in 500 ml of 1.7% saline infused over 24 hours compared to the same dose of diuretic infused over the same time period in 5% glucose.26 More work, as ever, is required.
ADH receptor antagonists
ADH receptor antagonists can treat of hyponatraemia in patients with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). Early trials of ADH receptor antagonists in patients with heart failure showed reductions in patient symptoms, and signs of congestion when added to standard diuretic treatment,27 while also increasing serum sodium concentrations more effectively than fluid restriction alone.28
However, EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) found no long-term survival benefit with tolvaptan compared to placebo for patients admitted with acute heart failure (n=4,133; average age 66 years; average LVEF 27.5%), despite increasing serum sodium levels among those who were hyponatraemic.29
EVEREST had the weakness that it took “all comers” into the trial, and ADH antagonists might well have a particular role in patients with hyponatraemia. At present, they are only ‘suggested’ for the treatment of resistant hyponatraemia in the context of congestion.21 Further trials are ongoing (NCT01644331 and NCT01584557).