Published ahead of print on March 20, 2008, doi:10.1164/rccm.200712-1876OC
© 2008 American Thoracic Society doi: 10.1164/rccm.200712-1876OC
Hyponatremia Predicts Right Heart Failure and Poor Survival in Pulmonary Arterial Hypertension1 Cardiovascular Division, Heart Failure/Transplant and Pulmonary Hypertension Programs, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania; 2 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland; 3 Division of Pulmonary and Critical Care, Emory University, Atlanta, Georgia; 4 Pulmonary Division, Vanderbilt University, Nashville, Tennessee; and 5 Division of Cardiology, Johns Hopkins University, Baltimore, Maryland Correspondence and requests for reprints should be addressed to Paul R. Forfia, M.D., Cardiovascular Division, Heart Failure/Transplant Program, University of Pennsylvania School of Medicine, 3400 Spruce Street, 6 Penn Tower, Philadelphia, PA 19104. E-mail: paul.forfia{at}uphs.upenn.edu 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 Conclusions: Hyponatremia is strongly associated with right heart failure and poor survival in PAH.
Key Words: hyponatremia • pulmonary heart disease • pulmonary hypertension • heart failure
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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 
2 = 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. 
