Pulmonary Artery Denervation for Pulmonary Arterial Hypertension - PADN-CFDA

Sep 18, 2022
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Scientific Foundation of China; Pulnovo provided all PADN catheters.
Date Presented:
09/18/2022
Date Published:
09/18/2022
Date Updated:
09/18/2022
Original Posted Date:
09/18/2022
References

Contribution To Literature:

The PADN-CFDA trial showed that pulmonary artery denervation along with drug monotherapy was superior to a sham procedure with drug monotherapy in improving functional and hemodynamic outcomes at 6 months among patients with Group I PAH not on baseline medications.

Description:

The goal of the trial was to evaluate the safety and efficacy of pulmonary artery denervation (PADN) among patients with Group I pulmonary arterial hypertension (PAH) who were not on PAH-specific drugs.

Study Design

This was a single-blinded trial. Patients were randomized in 1:1 fashion to either PADN (n = 63) or a sham PADN procedure (n = 65). PADN was performed in the peri-conjunctional area between the distal main pulmonary artery (PA) trunk and the ostium of the left main PA. For the sham PADN procedure, the PADN catheter was positioned at the target site but ablation was not performed. A phosphodiesterase-5 inhibitor, either sildenafil or tadalafil, was provided by the study and administered open-label to all patients after randomization.

  • Total screened: 186
  • Total randomized: 128
  • Duration of follow-up: 6 months
  • Mean patient age: 40 years
  • Percentage female: 82%

Inclusion criteria:

  • Age 18-70 years
  • World Health Organization (WHO) Group I PAH: mean pulmonary arterial pressure ≥25 mm Hg with pulmonary vascular resistance (PVR) >3 Wood units (WU) and pulmonary arterial wedge pressure (PAWP) <15 mm Hg, with a negative acute vasoreactivity test (for patients with idiopathic, heritable, or drug-induced PAH).
  • No PAH-specific medications for at least 30 days (other than diuretic or antithrombotic agents)

Other salient features/characteristics:

  • Etiology of PAH: Idiopathic: 54%
  • Time from diagnosis to screen: 3.5 years
  • WHO functional class II/III: 92%
  • Baseline use of diuretics: 70%, calcium channel blockers: 5%
  • Baseline PA pressures: systolic: 84 mm Hg, mean: 53 mm Hg, PVR: 11 WU

Principal Findings:

The primary outcome, change in 6-minute walk distance from baseline to 6 months, for PADN vs. sham, was: 56.9 vs. 26.7 m (p = 0.004).

Secondary outcomes for PADN vs. sham:

  • Change in PVR from baseline to 6 months: –3.0 vs. –1.9 (p = 0.003)
  • Reduction in N-terminal pro–B-type natriuretic peptide (NT-proBNP) from baseline to 6 months: –58.5% vs. –25.2% (p = 0.018)
  • Requirement for additional treatments: 1.6% vs. 7.7%
  • Improvement in WHO functional class by ≥1 grade: 42.9% vs. 23.1%

Interpretation:

The results of this trial show that PADN along with drug monotherapy was superior to a sham procedure plus monotherapy in improving functional and hemodynamic outcomes at 6 months among patients with Group I PAH not on baseline medications. No safety concerns were identified. This is an important advance and larger trials with longer-term follow-up are needed to assess this further. The appropriate patient population and its use relative to timing from PAH diagnosis are also unclear. For instance, it is unclear if this would be more beneficial among patients already on combination therapy, other etiologies of PAH, or those who have a recent diagnosis of PAH. It is also important to note that this therapy is unlikely to be curative, as higher sympathetic tone is not the only pathophysiological mechanism behind PAH, and in this trial, the mean PVR was still >8 in the PADN arm at 6 months. Finally, this trial was done in China and treatment responses may be different in other populations.

References:

Zhang H, Wei Y, Zhang C, et al. Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized Trial. JACC Cardiovasc Interv 2022;Sep 18:[Epub ahead of print].

Presented by Dr. Shao-Liang Chen at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2022), Boston, MA, September 18, 2022.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Statins, Heart Failure and Cardiac Biomarkers, Pulmonary Hypertension, Hypertension

Keywords: Arterial Pressure, Cyclic Nucleotide Phosphodiesterases, Type 5, Denervation, Diuretics, Fibrinolytic Agents, Hemodynamics, Hypertension, Pulmonary, Natriuretic Peptide, Brain, Primary Prevention, Pulmonary Arterial Hypertension, Pulmonary Wedge Pressure, Sildenafil Citrate, Tadalafil, TCT22, Transcatheter Cardiovascular Therapeutics, Vascular Diseases, Vascular Resistance


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