Published ahead of print on March 20, 2008, doi:10.1164/rccm.200712-1876OC Am. J. Respir. Crit. Care Med., Volume 177, Number 12, June 2008, 1364-1369 A more recent version of this article appeared on June 15, 2008
Submitted on December 21, 2007 Hyponatremia Predicts Right Heart Failure and Poor Survival in Pulmonary Arterial HypertensionPaul R Forfia1*,1 Cardiology Division, Heart Failure-Transplant and Pulmonary Hypertension Programs, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 2 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA, 3 Division of Pulmonary and Critical Care, Emory University, Atlanta, GA, USA, 4 Vanderbilt University, Nashville, TN, USA, 5 Division of Cardiology, Johns Hopkins University, Baltimore, MD, USA * To whom correspondence should be addressed. 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 PAH.
Methods-We prospectively followed 40 patients with PAH and examined the relationship between serum sodium and right heart function as well as survival.
Results-Hyponatremic subjects (Na Key words: hyponatremia, pulmonary heart disease, pulmonary hypertension, heart failure
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136 mEq/L) were more symptomatic (11/13 WHO class III/IV vs. 12/27 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) vs. normonatremic subjects. Hyponatremic subjects had higher right atrial pressure (14±6 vs. 9±3 mmHg; P<0.001), lower stroke volume index (21±7 vs. 32±10 ml/m2; P<0.01), larger RV:LV area ratio (1.8±0.4 vs. 1.3±0.4; P<0.001), and lower tricuspid annular plane systolic excursion (TAPSE; 1.4±0.3 vs. 2.0±0.6 cm; P=0.001), despite similar mean pulmonary artery pressure (49±10 vs. 47±12 mmHg; P=0.60). The one/two-year survival estimates were 93% (95% CI, 73-98%)/85% (95% CI, 65-94%), and 38% (95% CI, 14-63%)/15% (95% CI, 2-39%) for normonatremic and hyponatremic subjects, respectively (log-rank 
2=25.19, P<0.001). The unadjusted risk of death (HR) in hyponatremic and 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.