Abstract and Introduction
Aims To investigate in detail the correlates of dysnatremia, and to estimate its differential prognostic relevance in patients with heart failure with reduced or preserved LVEF.
Background Hyponatraemia has been shown to carry important prognostic information in patients with heart failure with reduced left ventricular ejection fraction (LVEF). However, exact serum sodium cut-off levels are not defined and the implications for heart failure with preserved ejection fraction (HF-pEF) are unclear. The prognostic value of hypernatraemia has not been investigated systematically. Therefore, the aim of this study was to investigate in detail the correlates of dysnatraemia, and to estimate its differential prognostic relevance in patients with heart failure with reduced or preserved LVEF.
Methods and results One thousand consecutive patients with heart failure of any cause and severity from the Würzburg Interdisciplinary Network for Heart Failure registry were included. Non-linear models for the association between serum sodium and mortality risk were calculated using restricted cubic splines and Cox proportional hazard regression. Median follow-up time for survivors was 5.1 years.
Results Independent correlates of dysnatraemia included guideline-recommended medication for chronic heart failure, indicators of renal function, and reverse associations with established cardiac risk factors. Overall mortality was 56%. Both hyponatraemia (n = 72) and hypernatraemia (n = 98) were associated with a significantly increased mortality risk: hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.60–2.77; and HR 1.91, 95% CI 1.49–2.45, respectively. A U-shaped association of serum sodium with mortality risk was found. Prognosis was best for patients with high normal sodium levels, i.e. 140–145 mmol/L.
Conclusions Both hypo- and hypernatraemia indicate a markedly compromised prognosis in heart failure regardless of LVEF. Sodium levels within the reference range carry differential information on survival, with serum levels of 135–139 mmol/L indicating an increased mortality risk.
The adverse impact of low serum sodium levels on prognosis in patients with heart failure and reduced left ventricular ejection fraction (HF-rEF) has been described in several outcome studies; it has, however, not specifically been investigated in patients with heart failure and preserved ejection fraction (HF-pEF). Furthermore, the precise pathomechanisms leading to hyponatraemia in heart failure are unclear. Neuroendocrine dysregulation of the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system (SNS), arterial underfilling with consecutive, baroceptor-mediated, non-osmotic vasopressin (AVP) secretion, chronic renal failure, and diuretic therapy are suggested as mechanisms of hyponatraemia, but we still lack a deeper understanding of their individual importance. Further, the cut-off values defining hyponatraemia are under debate. Their clinical utility remains uncertain, and the indication for the treatment of mild and moderate hyponatraemia (>125 mmol/L) in heart failure is controversially discussed. There are still limited data regarding a prognostic relevance of hypernatraemia in heart failure. One large registry observed an increased in-hospital mortality risk associated with hypernatraemia on admission, but this finding was not discussed in detail.
We therefore determined the correlates of dysnatraemia and investigated its prognostic value in heart failure, analysing serum sodium both as a continuous variable and in categories of hypo-, normo-, and hypernatraemia. We hypothesized that both hypo- and hypernatraemia indicate an unfavourable prognosis in patients with HF-rEF or HF-pEF.