Small Study Suggests Benefits of Denervation for Pulmonary Arterial Hypertension
SAN DIEGO, CA—Catheter-based denervation of the pulmonary artery is associated with improvements in functional outcomes and hemodynamic variables and a reduction in pulmonary arterial hypertension (PAH)-related events in patients with pulmonary hypertension of various causes, according to results from a small study presented March 16, 2015, at the American College of Cardiology/i2 Scientific Session.
From February 2013 to June 2014, Shao-Liang Chen, MD, of Nanjing First Hospital (Nanjing, China), and colleagues enrolled 28 patients (mean age 49 years; 39.3% male) a mean of 4.24 years after diagnosis with pulmonary hypertension. The most common etiology was idiopathic PAH (39.3%), following by secondary pulmonary hypertension from left heart disease (28.6%), congenital heart disease after surgical repair (14.3%), chronic thromboembolic pulmonary hypertension (10.7%), and connective tissue disease (7.1%).
For the before-and-after study, the patients initially stopped taking certain pulmonary hypertension drugs—phosphodiesterase type 5 inhibitors, prostacyclin, and endothelin receptor antagonists—for a washout period lasting 5 half-lives. After evaluation with right heart catheterization and cardiac echocardiography, they took standard pharmacotherapy for 6 months. That was followed by another washout period prior to all patients undergoing pulmonary artery denervation. A final evaluation was performed 6 months after the procedure.
The 6-minute walk distance (primary endpoint) increased during both medication treatment (from 361 to 373 m; P = .009) and following denervation (from 358 to 423 m; P < .001). The change in the distance was greater following denervation compared with medication both in absolute terms (65 vs 13 m; P = .002) and relative terms (23.9% vs 3.9%; P = .001).
On right heart catheterization, there were no changes in various hemodynamic measures on medical therapy, whereas denervation was associated with an increase in cardiac output and decreases in mean pulmonary artery pressure (PAP), systolic PAP, mean right atrial pressure (RAP), and pulmonary vascular resistance (PVR).
On echocardiography, there were improvements in mean and systolic PAP, mean RAP, RV systolic pressure, and RV Tei index on medical therapy, with gains seen on those measures—in addition to a reduction in pericardial fluid—following denervation.
Comparisons of those changes between groups revealed a greater increase in cardiac output and larger declines in catheterization-measured PVR and mean PAP and in echocardiography-assessed mean PAP, pericardial fluid, and RV Tei index following denervation.
World Health Organization (WHO) functional class improved to a similar degree with both medication therapy and denervation.
Clinical Outcomes Also Better
At 6 months, the rate of PAH-related events—which included a worsening of PAH, initiation of treatment with IV or subcutaneous drugs, lung transplantation, atrial septostomy, or all-cause death—was 42.9% in the medication group and 10.8% in the denervation group (P = .002). That difference was driven mostly by a higher rate of worsening PAH (36.0% vs 10.8%). There were no deaths, lung transplantations, or atrial septostomies and only 2 cases (in the medical therapy arm) of the need for IV or subcutaneous drugs.
Medical therapy also was tied to an increased rehospitalization rate (38.3% vs 14.4%; P = .018) and higher costs ($35,000 vs $6,000; P < .001).
The findings are consistent with the researchers’ earlier first-in-man study in 22 patients with idiopathic PAH who were unresponsive to standard medications, which was presented at the Transcatheter Cardiovascular Therapeutics symposium in October 2012 and later published in the Journal of the American College of Cardiology.
“Further randomized clinical [studies are] required to show the real benefit of pulmonary artery denervation in reducing mortality in patients with idiopathic [PAH], secondary pulmonary arterial hypertension, and also secondary pulmonary hypertension from left heart disease,” Dr. Chen said.
Source:Chen S-L. Pulmonary artery denervation for treatment of pulmonary arterial hypertension: results from a controlled before-and-after study. Presented at: American College of Cardiology/i2 Scientific Session; March 16, 2015; San Diego, CA.
- Dr. Chen reports receiving consulting fees/honoraria from Microport.