The findings of the Pulmonary artery denervation (PADN) trial, presented at the TCT conference on Sept 23rd have shown that PADN is associated with significant improvements in hemodynamic and clinical outcomes including 6-minute walk distance (6MWD) and pulmonary vascular resistance (PVR) in patients with combined pre- and post-capillary pulmonary hypertension CpcPH. The results of this study were simultaneously published in JACC: Interventions.
Pulmonary artery denervation (PADN) has been shown to improve hemodynamics of pulmonary arterial hypertension (PAH) in a series of patients. Additionally, the benefits of targeted medical therapy for patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) secondary to left-sided heart failure are unknown. Zhang et al. sought to assess the benefits of PADN among CpcPH patients in a prospective, randomized sham-controlled trial.
A total of 98 patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) were randomly assigned to PADN or sildenafil plus sham PADN. The definitions used included mean pulmonary arterial pressure ≥25 mmHg, pulmonary capillary wedge pressure >15 mmHg, and pulmonary vascular resistance (PVR] > 3.0 Woods Units. Standard medical therapy for heart failure was administered to all patients in both groups. The primary endpoint was the increase in the 6-minute walk distance (6MWD) at the 6-month follow-up. The secondary endpoint was alterations in PVR. Clinical worsening was assessed in a post-hoc analysis. The main safety endpoint was an occurrence of pulmonary embolism.
[perfectpullquote align=”full” bordertop=”false” cite=”” link=”” color=”” class=”” size=””]“The present randomized sham-controlled study is the first to report the safety and efficacy of PADN for patients with CpcPH . PADN is associated with significant improvements in hemodynamic and clinical outcomes in patients. However, given the small sample size, further studies are warranted to define its precise role in the treatment of this patient population.”- Dr. Shao-Liang Chen, M.D.[/perfectpullquote]
The investigators found that mean 6-minute walk distance was increased by 83m in the PADN study arm versus 15m in a sildenafil (Revatio, Viagra) arm at 6-months of follow-up (P<0.001). Additionally, PADN treatment was associated with a significantly lower PVR than in the sildenafil group (4.2 ± 1.5 vs. 6.1 ± 2.9 Wood Units, p = 0.001). From baseline to 6-month follow-up, the average reduction of PVR was 29.8% in the PADN group versus 3.4% in the sildenafil group. Zhang and his colleagues reported that clinical worsening was less frequent in the PADN group compared to the sildenafil group (16.7% vs. 40%, p = 0.014). At the end of the study, there were 7 all-cause deaths and 2 cases of pulmonary embolism (within 36 days for one sildenafil patient and 72 days for a PADN patient).
“The present randomized sham-controlled study is the first to report the safety and efficacy of PADN for patients with CpcPH . PADN is associated with significant improvements in hemodynamic and clinical outcomes in patients. However, given the small sample size, further studies are warranted to define its precise role in the treatment of this patient population,” Shao-Liang Chen, MD, of Nanjing Medical University in Nanjing, China stated.
“Treating patients with pulmonary hypertension can be challenging and they have an increased risk of mortality over time, so efforts should be made to assess therapies that can improve these patients’ outcomes as this study does,” noted B. Hadley Wilson, MD, of The Sanger Heart & Vascular Institute in Charlotte, North Carolina. “The data looks promising in a disease state where patients tend to do pretty poorly over the long haul,” Dr. Deepak Bhatt, Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital, Division of Cardiovascular Medicine, agreed. While he believed that larger studies were necessary to find a definitive answer, he appreciated the fact that it was being done in China as it could not presently be conducted in the United States due to lack of reimbursement and FDA approval.
To view the slides presented at TCT 2018, click here.