By Dr. Aswin Babu
Previous observational studies have signalled towards a benefit for pulmonary artery denervation (PADN) in treating pulmonary artery hypertension (PAH). However, to date, there are no randomised controlled trials (RCsT) in this field. The PADN-CFA (Pulmonary Artery Denervation for Pulmonary Arterial Hypertension: A Sham-Controlled Randomized trial) strives to answer the question whether PADN is superior when compared to medical therapy alone.
In this multi-centre, single-blinded trial, 128 patients with World Health Organisation (WHO) group 1 PAH were randomised in a 1:1 fashion to either PADN (n=63) or a sham PADN procedure (n=65). Both groups received either sildenafil or tadalafil after randomisation. Importantly, to be eligible for the trial, patients had to be drug naïve for any specific PAH therapies for at least 30 days.
Salient baseline characteristics included 82% of the cohort being female with a mean age of 40 years. Patients were followed up for a duration of 6 months. Around 54% of the PAH cases were idiopathic in aetiology. It was a very symptomatic cohort with 92% identified as either NYHA Class II or III. Additionally, the average mean PASP measured 53mmHg. The average pulmonary vascular resistance (PVR) was 11 wood units.
The primary outcome of change in a 6-minute walk distance after 6 months was significantly improved in the PADN group compared to the sham cohort (56.90 metres vs 26.7 metres, p =0.004). Secondary outcomes of improvement in PVR (p=0.003) and reduction in N-terminal pro–B-Type Natriuretic Peptide (p=0.018) were significantly better in the PADN group. Moreover, an absolute difference of 20% more patients improved their WHO functional status by > 1 grade when they underwent PADN therapies compared to no therapy.
This trial provides important insights to the role that pulmonary vasculature sympathetic tone contributes to the pathophysiology in PAH. PADN with medical therapy was far superior compared to medical therapy alone in enhancing functional, haemodynamic and biochemical outcomes at 6 months. However, larger studies assessing these effects over a longer period of time is required. Furthermore, PADN should be examined in different groups of PAH and the effects on more robust endpoints such as mortality and hospitalisation needs to be assessed.
