Hyponatremia Predicts Right Heart Failure and Poor Survival in Pulmonary Arterial Hypertension

Abstract

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 6 6 vs. 9 6 3 mm Hg; P , 0.001), lower stroke volume index (21 6 7 vs. 32 6 10 ml/m 2 ; 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 6 12 mm Hg; P 5 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 x 2 5 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.

Outcomes of hospitalisation for right heart failure in pulmonary arterial hypertension

“…Hyponatraemia is a well established prognostic factor in LHF [18,21,22], and has been attributed to neurohormonal activation mediated mostly by vasopressin and causing water retention. We have previously demonstrated that hyponatraemia is a strong indicator of poor long-term survival in patients with PAH [5]. In the current cohort, hyponatraemia was strongly associated with low SBP, which was itself a significant predictor for in-hospital mortality, suggesting mediation by neurohormonal activation in the context of low cardiac output.…”

“…The estimated glomerular filtration rate (eGFR) was calculated from creatinine values using the Modified Diet in Renal Disease equation [11]. Hyponatraemia was defined as serum Na f136 mEq?L -1 based on previous literature on PAH [5] and LHF [12,13].…”

“…The decision to exclude these conditions was based on the high prevalence of comorbidities in these patients that lead to hospitalisation unrelated to PAH. Although comorbid conditions are also common in CTD-PAH, we included these patients because of our long interest in their outcomes [5][6][7][8] and the fact that they represent the bulk of referral to our pulmonary hypertension programme. Patients with significant interstitial lung disease as previously defined (total lung capacity ,60% or 60-70% with significant interstitial radiological changes) were excluded [6][7][8].…”

Systemic Sclerosis-Associated Pulmonary Arterial Hypertension

“…A strong correlation between hyponatremia, as a marker of neurohormonal activation, and RV dysfunction and survival was demonstrated in a cohort of patients with PAH (23), where patients with SSc-PAH were more likely to be hyponatremic than patients with IPAH despite similar hemodynamics, suggesting possible differences in neurohormonal activation between the two groups. These as well as other specific markers of disease and disease severity should be identified.…”

Prognostic factors of acute heart failure in patients with pulmonary arterial hypertension

“…In left-heart disease, data suggest that these abnormalities are linked to survival [33], and it has been recently found that hyponatraemia is predictive of poor survival for PAH patients in stable condition. The pathophysiological mechanisms have been proposed to mirror those in left-heart failure [34]. Some studies have tested the efficacy of specific therapeutic interventions antagonising the vasopressin pathway in left-heart failure (outside the ICU setting), showing an improvement in serum level of sodium and dyspnoea, but no change in survival [35,36].…”