Editors' ChoicePulmonary Arterial Hypertension

A Reflex Cause of Pulmonary Hypertension

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Science Translational Medicine  09 Oct 2013:
Vol. 5, Issue 206, pp. 206ec168
DOI: 10.1126/scitranslmed.3007715

Idiopathic pulmonary arterial hypertension (iPAH) is a severe and progressive pulmonary vascular disease that causes narrowing of the blood vessels in the lung and leads to right heart failure and premature death. Currently, there are seven Food and Drug Administration?"approved therapies for this condition, and two more (macitentan and riociguat) are being considered for approval. Notwithstanding these advances, morbidity and mortality continue to be unacceptably high, and we need to better understand the pathogenesis of the disease and identify new therapeutic targets.

On the basis of some limited data, pulmonary hypertension has been suggested to be partly a result of a local neural reflex that originates from stretch receptors in or near the bifurcation of the main pulmonary artery. Stimulation of these baroreceptors leads to a limited activation of the adrenergic nervous system and vasoconstriction of the pulmonary artery. Chen et al. hypothesized that pulmonary artery denervation around its bifurcation could abolish this reflex by affecting either the stretch receptors or the efferent sympathetic nervous fibers. Supported by promising results in a dog model of pulmonary hypertension and the development of dedicated circular catheter for radiofrequency denervation, the authors conducted a pilot study in 21 patients with iPAH refractory to medical treatment. When compared with nontreated iPAH patients (n = 8), those who underwent pulmonary artery denervation (n = 13) were able to walk about 50% further in 6 min and showed improved right ventricular function and pulmonary vascular hemodynamics 3 months after the treatment.

These results are encouraging, especially because the authors saw no procedure-related complications, and all specific medications for iPAH were discontinued in the treatment group. We need to be cautious because the study was done in only one center with a limited number of patients and an apparently complex technique. Nevertheless, these results suggest further research to better understand the role of this local adrenergic reflex in iPAH and to develop pharmacological treatments with new modes of actions to treat this serious disease.

S.-L. Chen et al., Pulmonary artery denervation to treat pulmonary arterial hypertension: The Single-Center, Prospective, First-in-Man PADN-1 Study (First-in-Man Pulmonary Artery Denervation for Treatment of Pulmonary Artery Hypertension). J. Am. Coll. Cardiol. 62, 1092–1100 (2013). [Full Text]

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