Pulmonary Artery Denervation (PADN) Combined with a Phosphodiesterase-5 Inhibitor Improved Exercise Capacity, Cardiac Function, and Some Clinical Outcomes in Patients With Pulmonary Arterial Hypertension (PAH) in a Controlled Trial fictitious.
The primary endpoint of change from baseline in 6-minute walking distance increased in both groups at 30 days, with a median change at 6 months of 61 meters with denervation and 18 meters with sham treatment (P = 0.04).
The adjusted mean difference between the groups was 33.8 meters in favor of ANDS (95% CI, 16.7, 50.9; P
Walking distances did not improve in low-risk patients on REVEAL scores, while intermediate-to-high risk patients had “an extremely large increase” of 81.4 meters compared to 32.5 meters with a fictitious treatment (P = 0.007), lead researcher Shao-Liang Chen, MD, reported in a late-breaking session at Transcatheter Cardiovascular Therapeutics (TCT) 2022.
There were no procedural complications in either group. Chest pain was more common in the ANDS group but was mild and did not require analgesia.
“Treatment with DNA plus a PDE-5 inhibitor is very safe and significantly improves exercise capacity at 6 months compared to sham treatment,” said Chen, from Nanjing First Hospital, Nanjing Medical University, China.
Previous observational studies, including TROPHY 1, have shown that pulmonary artery denervation improves hemodynamic and exercise capacity in patients with PAH, but its efficacy and safety have not been studied in a clinical setting. randomized trial, he noted.
The current trial, known as ANDA-CFDA, was conducted at 11 centers in China between January 2018 and June 2021. The researchers recruited 128 patients (mean age, 40.8 years) with Group 1 PAH from the World Health Organization not taking any PAH-specific medication for at least 30 days prior to randomization and assigned them to receive ANDS or a sham procedure, plus either post-procedure sildenafil, 25 mg three times daily day, or tadalafil, 20 to 40 mg per day.
Denervation was performed at three sites at the junction area between the distal main trunk and the left ostial branch for 120 seconds at 45–50°C and 15 W or less. Chen invented the DNA catheter (Pulnovo Medical) but is not the patent holder.
At baseline, the mean 6-minute walk distance was 401 meters, the mean pulmonary arterial pressure was 53.9 mm Hg, the mean pulmonary vascular resistance was 10.9 Wood units, and the mean pro-natriuretic peptide level was N-terminal brain (NT-proBNP) was 2345. pg/mL.
As simultaneously reported in JACC: Clinical InterventionsDNA led to greater reductions at 6 months in NT-proBNP levels (–58.5% vs –25.2%; P = 0.018) and pulmonary vascular resistance (PVR) (–27% vs -14.8%; P = 0.003).
Cardiac function improved to a greater degree in DNA than in the sham group, including right atrial pressure (–1.7 mm Hg versus 0.4 mm Hg) and right ventricular fractional area change ( 10.4% versus -0.6%) but, in particular, the annular tricuspid plane systolic excursion (4.3 mm versus -0.1 mm) and global longitudinal deformation of the right ventricle (-2.9% versus – 0.1%), observed Chen.
Mean pulmonary arterial pressure at 6 months was –7.8 mm Hg versus –3.5 mm Hg, respectively.
During follow-up, clinical worsening—defined as worsening of pulmonary arterial hypertension, arterial septostomy, listing for lung transplantation, or death from any cause—occurred in one ANDS patient and nine controls (risk relative, 0.11; 95% CI, 0.01 – 0.87).
Guest speaker, Ori Ben-Yuhuda, MD, Cardiovascular Research Foundation, New York, asked how patients were blinded, particularly because the procedure was associated with some pain, and whether longer-term follow-up was planned.
“In the TROPHY study, we saw a decrease in the effectiveness of using an ultrasound catheter after 6 months. So this is a significant long-term issue,” he said. declared.
Chen reported that a blinded questionnaire showed that 96.8% of ANDS-treated patients and 95.4% of sham-treated patients believed they had received active treatment, and said 12-month follow-up was very important, as are larger trials with clinical outcomes as the primary endpoint. .
Asked at a previous press conference why they chose not to enroll patients already receiving PAH medication, Chen said PAH is handled differently in China than in Western countries and that conducting the trial during the COVID pandemic created challenges.
Commenting on the results, Riyaz Bashir, MD, director of vascular and endovascular medicine, Temple Heart & Vascular Institute, Philadelphia, Pennsylvania, said lecoeur.org | Medscape Cardiology the study is small but important because all patients started with a clean slate, without medication, and they saw a difference of 33 meters in 6 minutes of walking.
“There are a lot of challenges with walk tests,” he acknowledged. “Future trials should use, as the primary endpoint, an objective hemodynamic endpoint, which they had – PVR – and then combine that with clinical endpoints.”
Still, the study “helps us move down the path because it’s data we can trust, as opposed to registry data,” Bashir said. “What it tells us is that there is a benefit signal for the denervation principle, but we need to develop better devices, use better devices, and use better parameters.”
Pulnovo Medical announced in July that it was seeking approval from the U.S. Food and Drug Administration to begin the global ANDS clinical trial, similar to the present study in design and with current co-author Gregg Stone, MD, as Chairman of the Steering Committee.
Also commenting for lecoeur.org | Medscape CardiologyDipti Itchhaporia, MD, past president of the American College of Cardiology and interventional cardiologist at the Hoag Heart & Vascular Institute, Newport Beach, Calif., said, “This is a provocative, well-done, sham, small, but bigger study. trials are needed” for these often very sick patients.
“They only made one drug, and these sick patients sometimes benefit from multiple therapies, so the question is, which is the best population?” she says.
Itchhaporia also pointed out that several drugs can be expensive, difficult to obtain in some countries, and often difficult to adhere to in the long term. “All of these things are problems and that’s where therapy like this can seem like a good alternative, especially because sometimes people don’t feel well on these drugs.”
The study received grants from the National Scientific Foundation of China and was funded by Nanjing First Hospital. Pulnovo supplied all DNA catheters. Chen has received speaker fees from Microport, Pulnovo, Boston International Scientific, Medtronic, Sanofi, and BioMed and grants from the National Science Foundation of China. Co-author Gregg Stone, MD, has multiple industry connections. Itchhaporia reports having no relevant disclosures.
JACC Cardiovascular Interv. Published online September 18, 2022. Summary