Safety and Efficacy of a Novel Atrial Flow Regulator in Patients With Severe Pulmonary Arterial Hypertension: The AFR-Prophet Study

Background: Pulmonary arterial hypertension (PAH) is a progressive, often fatal disease.Balloon atrial septostomy may relieve symptoms or serve as a bridge to transplant, but carries risks of variable shunting and reocclusion.The atrial flow regulator (AFR) provides a sustained interatrial shunt with a defined shunt size.Methods: AFR-Prophet is a prospective, multicenter study evaluating the mechanism of action and safety of AFR in high-risk PAH.Of 32 screened patients, 25 underwent the procedure.The primary end point was serious adverse device effects or procedure-related events at 90 days.Secondary end points included longer-term safety and changes in functional, hemodynamic, and structural parameters.Results: Among 25 patients, 24 received the implant.One patient died prior to implantation because of iatrogenic pericardial tamponade.At 90 days, 7 serious adverse device effects occurred (28%): 3 device-related (oxygen desaturation) and 4 procedure-related.At 3 months, AFR implantation reduced pulmonary vascular resistance and improved cardiac index, despite lower arterial oxygen saturation.Echocardiography showed a smaller right ventricular (RV) end-diastolic diameter and RV/left ventricular ratio, a higher tricuspid annular plane systolic excursion and RV fractional area change, and improved RV-pulmonary artery coupling.Shunt flow was detected in all but 1 patient.NT-proBNP levels decreased, New York Heart Association class improved (>1 class) in 66% of patients, and 6-minute walk distance increased.During the 1-year follow-up, 9 patients died and 3 underwent lung transplantation.Conclusions: Atrial flow regulator therapy in PAH was associated with improved RV function, enhanced RV-pulmonary artery coupling, and better overall cardiac performance.Despite the dismal prognosis of advanced PAH, signals of improved symptoms and physical capacity support interatrial shunting as a potential therapeutic option for carefully selected, even high-risk patients.