Hemodynamic, functional, and clinical responses to pulmonary artery denervation in patients with pulmonary arterial hypertension of different causes: phase II results from the Pulmonary Artery Denervation-1 study

Shao-Liang Chen, Hang Zhang, Du-Jiang Xie, Juan Zhang, Ling Zhou, Alexander M K Rothman, Gregg W Stone, Shao-Liang Chen, Hang Zhang, Du-Jiang Xie, Juan Zhang, Ling Zhou, Alexander M K Rothman, Gregg W Stone

Abstract

Background: The mechanisms underlying pulmonary arterial hypertension (PAH) are multifactorial. The efficacy of pulmonary artery denervation (PADN) for idiopathic PAH treatment has been evaluated. This study aimed to analyze the hemodynamic, functional, and clinical responses to PADN in patients with PAH of different causes.

Methods and results: Between April 2012 and April 2014, 66 consecutive patients with a resting mean pulmonary arterial pressure ≥25 mm Hg treated with PADN were prospectively followed up. Target drugs were discontinued after the PADN procedure. Hemodynamic response and 6-minute walk distance were repeatedly measured within the 1 year post PADN follow-up. The clinical end point was the occurrence of PAH-related events at the 1-year follow-up. There were no PADN-related complications. Hemodynamic success (defined as the reduction in mean pulmonary arterial pressure by a minimal 10% post PADN) was achieved in 94% of all patients, with a mean absolute reduction in systolic pulmonary arterial pressure and mean pulmonary arterial pressure within 24 hours of -10 mm Hg and -7 mm Hg, respectively. The average increment in 6-minute walk distance after PADN was 94 m. Worse PAH-related events occurred in 10 patients (15%), mostly driven by the worsening of PAH (12%). There were 8 (12%) all-cause deaths, with 6 (9%) PAH-related deaths.

Conclusions: PADN was safe and feasible for the treatment of PAH. The PADN procedure was associated with significant improvements in hemodynamic function, exercise capacity, and cardiac function and with less frequent PAH-related events and death at 1 year after PADN treatment. Further randomized studies are required to confirm the efficacy of PADN for PAH.

Clinical trial registration: URL: http://www.chictr.trc.com.cn. Unique identifier: chiCTR-ONC-12002085.

Keywords: arterial pressure; denervation; familial primary pulmonary hypertension; hemodynamics; pulmonary artery.

© 2015 The Authors.

Figures

Figure 1.
Figure 1.
Pulmonary arterial angiography, position of electrodes, and pulmonary artery denervation (PADN) procedure. (I) Anterior-posterior and cranial (200) view of the pulmonary arterial angiograph. (II) The red line represents the lateral wall of the main pulmonary artery (MPA), the blue line represents the anterior wall of the left pulmonary artery (LPA), and the point where the 2 lines intersect is point A; the intersection of the yellow (posterior wall of the LPA) and red lines is point B, which is 1 to 2 mm posterior to point A; the green line starts from the inferior wall of the right pulmonary artery (RPA) and ends at point A, and point C localizes at this level and 1 to 2 mm anterior to point A. (III) A pulmonary artery denervation catheter with 10 electrodes is positioned at the distal MPA, with electrodes A, B, and C at points A, B, and C, respectively.
Figure 2.
Figure 2.
Dynamic changes in mean pulmonary arterial pressure (A), pulmonary vessel resistance (B), 6-minute walk distance (C), and N-terminal pro–brain natriuretic peptide (NT pro-BNP; D, after transferred to log data) levels. All variables improved significantly at the 6-month follow-up, without any additional significant change between the 6-month and the 1-year follow-up.
Figure 3.
Figure 3.
Kaplan–Meier survival analysis. The 1-year Kaplan–Meier–estimated rate of pulmonary arterial hypertension (PAH)–related events was 15.2%. PADN indicates pulmonary artery denervation.

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