Prognostic Significance of Sympathetic Nervous System Activation in Pulmonary Arterial Hypertension

Rationale The sympathetic nervous system has been reported to be activated in pulmonary arterial hypertension (PAH). Objectives: We investigated the prognostic significance of muscle sympathetic nervous system activity (MSNA) in PAH. Methods: Thirty-two patients with PAH were included in the study and underwent a measurement of MSNA over a 6-year period of time. They had undergone a concomitant evaluation of New York Heart Association (NYHA) functional class, a 6-minute walk distance (6MWD), an echocardiographic examination, and a right heart catheterization for diagnostic or reevaluation purposes. The median follow-up time was 20.6 months (interquartile range, 45.8 mo). Clinical deterioration was defined by listing for transplantation or death. Measurements and Main Results: Seventeen patients presented with clinical deterioration. As compared with the 15 others, they had an increased MSNA (80 +/- 12 vs. 52 +/- 18 bursts/min; P < 0.001) and heart rate (88 +/- 17 vs. 74 +/- 12 bpm; P = 0.01), a lower 6MWD (324 +/- 119 vs. 434 +/- 88 m; P < 0.01) and a deteriorated NYHA functional class (3.6 +/- 0.5 vs. 2.9 +/- 0.8; P < 0.001). The hemodynamic variables were not different. MSNA was directly related to heart rate and inversely to 6MWD. A univariate analysis revealed that increased MSNA and heart rate, NYHA class IV, lower 6MWD, and pericardial effusion were associated with subsequent clinical deterioration. A multivariate analysis showed that MSNA was an independent predictor of clinical deterioration. For every increase of 1 burst/minute, the risk of clinical deterioration during follow-up increased by 6%. Conclusions: Sympathetic nervous system activation is an independent predictor of clinical deterioration in pulmonary arterial hypertension.