Low Sodium Predicts Worse Prognosis in Pulmonary Arterial Hypertension

By Charles Bankhead
PHILADELPHIA, 14 june 2008-- Hyponatremia in patients with pulmonary arterial hypertension portends advanced right heart failure and poor survival, investigators here found.
As compared with patients who had normal sodium levels, those with hyponatremia had more symptomatic heart failure, more peripheral edema, and higher hospitalization rates, Paul R. Forfia, M.D., of the University of Pennsylvania, and colleagues reported in the June 15 issue of the American Journal of Respiratory and Critical Care Medicine.
"Serum sodium has important implications regarding the right heart dysfunction, clinical right heart failure, and patient outcome, and should not be overlooked in the clinical assessment of patients with [pulmonary arterial hypertension]," the authors concluded.
Hyponatremia is a recognized marker of advanced left heart failure and is an independent predictor of poor outcome, but the influence of hyponatremia in pulmonary arterial hypertension and right heart failure is less clear, the authors said.
Given the prevalence and prognostic significance of right heart failure in pulmonary arterial hypertension, Dr. Forfia and colleagues examined the impact of hyponatremia on right-sided failure and prognosis.
They prospectively followed 40 patients with pulmonary arterial hypertension, 13 of whom had hyponatremia, defined as ≤136 mEq/L.
Mean pulmonary artery pressure was 49 mm Hg in patients with hyponatremia and 47 mm Hg in those with normal sodium levels.
Compared with the 27 patients who had normal sodium levels, hyponatremic patients differed significantly with respect to:
Prevalence of World Health Organization class III/IV heart failure, 11 of 13 versus 12 of 27, P=0.02
Prevalence of peripheral edema, 69% versus 26%, P=0.009
Hospitalization rate, 85% versus 41%, P=0.009
Right atrial pressure, 14 versus 9 mm Hg, P<0.001
Stroke volume index, 21 versus 32 ml/m2, P<0.01
Right:Left ventricular area ratio, 1.8 versus 1.3, P<0.001
Tricuspid annular plane systolic excursion, 1.4 versus 2.0 cm, P=0.001
The one- and two-year estimated survival was 93% and 85% in the normonatremic patients versus 38% and 15% in those with hyponatremia (P<0.001).
Hyponatremic patients had an unadjusted mortality hazard ratio of 10.16 versus patients with normal sodium and had a median survival of 8.5 months.
Hyponatremia remained an independent predictor of outcome after adjustment for WHO class, diuretic use, right atrial pressure, and cardiac index.
"Our findings are consistent with prior studies showing that the prognostic significance of [hyponatremia] in patients with [left heart failure] occurs independent of hemodynamics and other measures of ventricular dysfunction," the authors said.
"Taken together, our data suggest that a low serum sodium concentration in [pulmonary arterial hypertension] is an integrative measure that signifies a syndrome of right heart dysfunction and ensuing circulatory maladaptation, analogous to the pathophysiologic paradigm of [left heart failure]."
The authors pointed out several limitations of the study, including the fact that for more than half of the patients, pulmonary hypertension was associated with connective tissue disease. "This population has been shown by our group and others to have worse survival when compared with patients with idiopathic [pulmonary arterial hypertension]," they said.
"Thus, our survival and hazard analyses may be biased by inclusion of a population of patients who were more likely to die, regardless of serum sodium, and thus our findings may be less applicable to other [pulmonary arterial hypertension] populations."
They said that their survival analyses may have also been skewed by lead-time bias because patients with established disease may have been more likely to die in the follow-up period than newly diagnosed patients.
The authors declared no conflicts of interest.
Primary source: American Journal of Respiratory and Critical Care MedicineSource reference:Forfia PR, et al "Hyponatremia predicts right heart failure and poor survival in pulmonary arterial hypertension" Am J Respir Crit Care Med 2008; 177: 1364-1369.