Patients with combined pre and postcapillary pulmonary hypertension (CpcPH) secondary to left-sided heart failure (HF) who underwent a pulmonary artery denervation (PADN) procedure had significant improvements in hemodynamic and clinical outcomes at 6 months, compared with patients who underwent a sham procedure, in the PADN-5 trial.
Among 98 patients with CpcPH assigned to receive either pulmonary denervation or sildenafil plus a sham procedure, PADN was associated with significantly better 6-minute walk distance and significantly lower pulmonary vascular resistance at 6 months, reported Shao-Liang Chen.
The benefits of PADN were seen in patients with both ejection-fraction preserved HF and ejection-fraction reduced HF, he said here at Transcatheter Cardiovascular Therapeutics 2018. The study was published online in JACC: Cardiovascular Interventions to coincide with the presentation.
But one clinical trials specialist questioned whether the patients in the trial – especially men – could truly be unaware of their treatment assignment, considering that sham-operated controls received sildenafil, which is approved for the treatment of erectile dysfunction .
In PADN5, investigators randomly assigned 98 patients – 60 men and 38 women with a mean age of 63 years – with CpcPH to receive anti-HF therapies (including calcium-channel blockers, β-adrenergic receptor blockers, digoxin , diuretics, angiotensin-converting –enzyme inhibitors, and angiotensin-receptor blockers) plus either sildenafil and a sham procedure or PADN.
Pulmonary artery hypertension
The investigators decided to use sildenafil because results from a meta-analysis previously demonstrated the beneficial effects of the drug in patients with pulmonary artery hypertension. However, in international treatment guidelines, neither sildenafil nor other therapies for pulmonary artery hypertension are recommended for patients with CpcPH, I have acknowledged.
CpcPH was defined as a pulmonary arterial pressure of at least 25 mm Hg, pulmonary capillary wedge pressure above 15 mm Hg, and pulmonary vascular resistance above 3.0 Wood units.
PADN was performed in the peri-lateral area between the distal main trunk and the ostial left branch, with ablation at each point performed at temperatures of at least 45 ° C and energy of 20 watts or less over 120 seconds. Hemodynamic parameters were continuously monitored and recorded throughout the procedure.
"To simulate the true PADN procedure, discussions among the operator, technician, and nurses, as well as beep sounds from the generator, were recorded on a cell phone from a previous PADN procedure. patient to believe that a PADN procedure was being performed, "the investigators write in the study publication .
At the briefing, I have pointed out that wedge pressure went down in the denervation group, whereas it would be expected to rise because of a reduction in precapillary vasoconstriction, an effect seen with prostacyclin and other drugs used to treat pulmonary hypertension.