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 5 0.02), had more peripheral edema (69 vs. 26%; P 5 0.009), and had higher hospitalization rates (85 vs. 41%; P 5 0.009) than normonatremic subjects. Hyponatremic subjects had higher right atrial pressure (14 66vs.9 63mmHg;P ,0.001),lowerstrokevolumeindex(21 67 vs. 32 6 10 ml/m2; P , 0.01), larger right ventricular:left ventricular area ratio (1.8 6 0.4 vs. 1.3 6 0.4; P , 0.001), and lower tricuspid annular plane systolic excursion (1.4 6 0.3 vs. 2.0 6 0.6 cm; P 5 0.001), despite similar mean pulmonary artery pressure (49 6 10 vs. 47 612 mm Hg;P 50.60). 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 x2 525.19,P ,0.001).Theunadjustedriskofdeath(hazardratio)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.