Relation of Serum Sodium Level to Long-Term Outcome After a First Hospitalization for Heart Failure With Preserved Ejection Fraction

Hyponatremia is a predictor of adverse short-term outcomes in patients with acute heart failure (HF). The impact of hyponatremia on long-term survival in patients with HF with preserved ejection fraction (HFPEF) has not been evaluated. Our aim was to prospectively assess the impact of baseline natremia and changes in sodium level during hospitalization on 7-year outcome in 358 patients surviving a first hospitalization for HFPEF. On admission, hyponatremia (sodium <136 mEq/L) was diagnosed in 91 patients (25.4%). Baseline hyponatremia was associated with an increased risk of overall (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.50 to 2.61) and cardiovascular mortality (HR 1.92, 95% CI 1.36 to 2.73). After adjustment for covariates, the relations remained significant. Seven-year relative survival (observed/expected survival) of hyponatremic patients was lower than that of patients with normal baseline natremia (31% vs 63%). The association of sodium and risk of death appeared linear across quartiles of baseline natremia and slightly stronger at the lowest of sodium values. At discharge, 45 patients with low baseline sodium had normal natremia (49%) and 46 had persistent hyponatremia (51%). Patients with normalized natremia at discharge had excess 7-year overall mortality compared with the normonatremic group (HR 1.50, 95% CI 1.03 to 2.19). Patients with persistent hyponatremia had the lowest 7-year survival (HR 2.67, 95% CI 1.89 to 3.78). After adjustment for covariates, patients with persistent hyponatremia had an impressive increase in relative risk of overall mortality compared with patients with normal baseline natremia. In conclusion, hyponatremia is a powerful predictor of long-term mortality in patients with HFPEF. Patients with HFPEF and persistent hyponatremia are at high risk of adverse outcomes.