Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension

Rationale: Hyponatremia is associated with decompensated heart failure and poor prognosis in patients with left ventricular systolic dysfunction. Objectives: We sought to determine if hyponatremia is associated with right heart failure and worse prognosis in patients with pulmonary arterial hypertension (PAH). Methods: We prospectively followed 40 patients with PAH and examined the relationship between serum sodium and right heart function as well as survival. Measurements and Main Results: Subjects with hyponatremia (Na ≤ 136 mEq/L) were more symptomatic (11/13 World Health Organization [WHO] class III/IV vs. 12/27 WHO class III/IV; P = 0.02), had more peripheral edema (69 vs. 26%; P = 0.009), and had higher hospitalization rates (85 vs. 41%; P = 0.009) than normonatremic subjects. Hyponatremic subjects had higher right atrial pressure (14 ± 6 vs. 9 ± 3 mm Hg; P < 0.001), lower stroke volume index (21 ± 7 vs. 32 ± 10 ml/m²; P < 0.01), larger right ventricular:left ventricular area ratio (1.8 ± 0.4 vs. 1.3 ± 0.4; P < 0.001), and lower tricuspid annular plane systolic excursion (1.4 ± 0.3 vs. 2.0 ± 0.6 cm; P = 0.001), despite similar mean pulmonary artery pressure (49 ± 10 vs. 47 ± 12 mm Hg; P = 0.60). The 1- and 2-year survival estimates were 93% (95% confidence interval [CI], 73-98%) and 85% (95% CI, 65-94%), and 38% (95% CI, 14-63%) and 15% (95% CI, 2-39%) for normonatremic and hyponatremic subjects, respectively (log-rank χ² = 25.19, P < 0.001). The unadjusted risk of death (hazard ratio) in hyponatremic compared with normonatremic subjects was 10.16 (95% CI, 3.42-30.10, P < 0.001). Hyponatremia predicted outcome after adjusting for WHO class, diuretic use, as well as right atrial pressure and cardiac index. Conclusions: Hyponatremia is strongly associated with right heart failure and poor survival in PAH.