Hyponatremia was shown to be a marker of adverse prognosis in patients with heart failure (HF). In previous studies, it has been associated with higher doses of diuretics in an acute decompensated setting, as well as spironolactone use in ambulatory patients. We sought to investigate the relationship between sodium levels and mortality, as well as the relationship between hyponatremia and diuretic medication doses in ambulatory patients treated according to modern guidelines. Data was obtained retrospectively on 818 patients followed for HF in a specialized clinic over a 1-year period. Patients with at least one serum sodium value < 135 mmol/L during follow-up were assigned to the hyponatremic group, while others were assigned to the normonatremic group. Overall prevalence of HF with preserved ejection fraction (HFpEF) was 29.3%. Prevalence of hyponatremia was 13.2% (n=108). Mortality was 19.4% in the hyponatremic group versus 6.1% in the normonatremic group (OR 3.74, 95% CI 2.12-6.61, p < 0.001). On multivariate analysis to correct for baseline factors, each decrease of 1 mmol/L mean serum sodium increased relative mortality risk by 15.9% (95% CI 7.4% to 23.6%; p < 0.001). The absolute reduction in eGFR from baseline was greater in the hyponatremic group (median -9.6 vs -4.0 mL/min/1.73m2, p < 0.001). Hyponatremia was associated with increased use of loop diuretics (LD) (88.0% of patients vs 68.2% in the normonatremic group, p < 0.001), mineralocorticoid receptor antagonists (MRA) (75.9 vs 52.5%, p < 0.001) and metolazone (20.4 vs 3.2%, p < 0.001). Patients in the hyponatremic group had higher maximum daily doses of LD (median 80 mg/day vs 20 mg/day, p < 0.001) and MRA (median 25 mg/day vs 12.5 mg/day, p < 0.001). There was a significant LD regimen escalation following a low serum sodium value (median dose increasing from 40 to 80 mg/day, p = 0.002). In ambulatory HF patients, hyponatremia is still a prevalent problem. Even if within the normal range, mean and nadir serum sodium levels are inversely associated with mortality risk. A majority of patients were using a MRA, and this medication class was associated with hyponatremia. Hyponatremia was also associated with higher LD requirements and greater use of metolazone, which are surrogates of increased diuretic resistance. Further trials should focus on alternative medications directed at hyponatremia as a therapeutic target, in order to bypass diuretic resistance and decrease mortality in this subset of patients.View Large Image Figure ViewerDownload Hi-res image Download (PPT)